PROTAC(H-PGDS)-7 is a Hematopoietic prostaglandin D synthase (H-PGDS) PROTAC degrader, with a DC50 of 17.3 pM.

L-Glutamine-1-13C (L-Glutamic acid 5-amide-1-13C) is the 13C-labeled L-Glutamine. L-Glutamine (L-Glutamic acid 5-amide) is a non-essential amino acid present abundantly throughout the body and involved in many metabolic processes. L-Glutamine provides a source of carbons for oxidation in some cells.

L-Glutamine-5-13C (L-Glutamic acid 5-amide-5-13C) is the 13C-labeled L-Glutamine. L-Glutamine (L-Glutamic acid 5-amide) is a non-essential amino acid present abundantly throughout the body and involved in many metabolic processes. L-Glutamine provides a source of carbons for oxidation in some cells.

BIM-26226, gastrin-releasing peptide, is a potent and selective antagonist of bombesin receptor. BIM-26226 inhibits BN- or GRP-stimulated amylase release with IC50s in the nanomolar range. BIM-26226 can be used for the research of cancer.

L-Glutamine-15N2 (L-Glutamic acid 5-amide-15N2) is the 15N-labeled L-Glutamine. L-Glutamine (L-Glutamic acid 5-amide) is a non-essential amino acid present abundantly throughout the body and involved in many metabolic processes. L-Glutamine provides a source of carbons for oxidation in some cells.

L-Glutamine-15N-1 (L-Glutamic acid 5-amide-15N-1) is the 15N-labeled L-Glutamine. L-Glutamine (L-Glutamic acid 5-amide) is a non-essential amino acid present abundantly throughout the body and involved in many metabolic processes. L-Glutamine provides a source of carbons for oxidation in some cells.

4-Methylhistamine (dihydrochloride) is the potent agonist of histamine 4 receptor (H4R). 4-Methylhistamine (dihydrochloride) has the potential for the research of immune-related diseases such as cancer and autoimmune disorders.

(R)-(-)-α-Methylhistamine dihydrochloride is a potent, selective and brain-penetrant agonist of H3 histamine receptor, with a Kd of 50.3 nM. (R)-(-)-α-Methylhistamine dihydrochloride can enhance memory retention, attenuates memory impairment in rats.

A6770 is an orally active, potent sphingosine 1-phosphate (S1P) lyase (S1PL) inhibitor. A6770 is phosphorylated and the phosphorylated form directly inhibits S1P lyased.A6770, a potential key metabolite of THI, induces a [3H]dhS1P increase.

Zendusortide is a sortilin binding peptide.

Heterobivalent ligand-1 (compound 26) is a heterobivalent ligand for the Adenosine A 2A-dopamine D 2 receptor heteromer (KDB1 A2AR=2.1 nM, KDB1 D2R= 0.13 nM).

(±)-Muscarine chloride is the racemate of Muscarine chloride. Muscarine is a prototype muscarinic acetylcholine receptor agonist.

CKLF1-C27, a C-terminal peptide of CKLF1, binds to CCR4 receptor and activates ERK1/2 pathway. CKLF1-C27 can abrogate the effect of CKLF1 on cells by competing for CCR4 receptor. CKLF1-C27 shows great effect on promoting proliferation on HUVECs. CKLF1-C27 has the potential for psoriasis research.

CKLF1-C27, a C-terminal peptide of CKLF1, binds to CCR4 receptor and activates ERK1/2 pathway. CKLF1-C27 can abrogate the effect of CKLF1 on cells by competing for CCR4 receptor. CKLF1-C27 shows great effect on promoting proliferation on HUVECs. CKLF1-C27 has the potential for psoriasis research.

Sumatriptan (GR 43175 free base) is an orally active 5-HT1 receptor agonist with Kis of 17 nM, 27 nM and 100 nM for 5-HT1D, 5-HT1B and 5-HT1A receptors, respectively. Sumatriptan can be used for migraine headache research.

CGS 12066 (dimaleate) dimaleate is a selective 5-HT1B receptor agonist with an IC50 of 51 nM.

RS 67333 hydrochloride is a potent and selective 5-HT4 receptor (5-HT4R) partial agonist with a pKi of 8.7 in guinea-pig striatum. RS 67333 hydrochloride exhibits lower affinities at several other receptors including 5-HT1A, 5-HT1D, 5-HT2A, 5-HT2C, dopamine D1, D2 and muscarinic M1-M3 receptors. RS 67333 hydrochloride has neuroprotective effects, and can be used for Alzheimer's disease research.

MS 245 oxalate is a potent antagonist of 5-HT6 receptor with a Ki of 2 nM.

Gentisein (NSC 329491), the major metabolite of Mangiferin, shows the most potent serotonin uptake inhibition with an IC50 value of 4.7 µM.

5-HT6/5-HT2AR antagonist-1 is a potent dual 5-HT6/5-HT2AR antagonist with Ki values of 11 nM and 39 nM, respectively.

A1AR antagonist 2 (compound 18h) is a potent A1 adenosine receptor (AR) antagonist with Kis of 1.49, 10.2, and 50.1 nM for hA1, hA2A and hA2B, respectively.

MRS1334 is a potent and selective human adenosine A3 receptor antagonist with Kis of 2.69 nM, >100 nM, >100 nM for hA3, rA1, rA2A, respectively. MRS1334 blocks the protective effect of Cl-IB-MECA leading to significant bradycardia and elevated ST segment.

Adenosine receptor antagonist 3 is a potent antagonist of adenosine receptor. Adenosine receptor antagonist 3 has the potential for the research of cancer disease (extracted from patent WO2019233994A1, compound 1).

IHCH-3064 is a dual-acting compounds targeting Adenosine A2A Receptor and HDAC. IHCH-3064 exhibits potent binding to A2AR (Ki=2.2 nM) and selective inhibition of HDAC1 (IC50=80.2 nM), with good antiproliferative activity against tumor cell lines in vitro. IHCH-3064 is a tumor immunotherapeutic agent.

A2A/A1 AR antagonist-1 (compound 1a) is dual potent A2A/A1 AR antagonist with Kis of 5.58 and 24.2 nM, respectively. A2A/A1 AR antagonist-1 has the potential for the research of ischemic stroke.

Adenosine receptor antagonist 2 is an orally active A2a/A2b adenosine receptor antagonist with IC50s of 1 nM and 3 nM, respectively. Adenosine receptor antagonist 2 has anti-tumor activity.

VUF-5574 is a selective antagonist of adenosine A3 receptor with a Ki of 4.03 nM for the recombinant human receptor.

PSB36 is a potent and selective antagonist of adenosine A1 receptor, with Kis 0.12 nM, 187 nM, 552 nM, 2300 nM, and 6500 nM for rA1, hA2B, rA2A, hA3 and rA3 receptors respectively. PSB36 can be used for the research of hyperalgesia.

A1AR antagonist 1 (compound 18g) is a potent A1 adenosine receptor (AR) antagonist with Kis of 2.08, 6.91, and 31.2 nM for hA1, hA2A and hA2B, respectively.

Prazobind (SZL 49), a prazosin analog, is a potent alpha 1-adrenoceptor blocker. Prazobind competes for alpha 1-adrenoceptor binding sites with a similar potency (IC50=1 nM) in tissues enriched in both the alpha 1A (hippocampus) and alpha 1B (liver) subtypes.

A-61603 is a selective α1A-adrenergic receptor agonist. A-61603 increases the frequency of spontaneous Ca2+ transients in rat ventricular myocytes in vitro.

Bevantolol is a selective β-1 adrenoceptor antagonist. Bevantolol can be used for the research of angina pectoris and hypertension.

A55453 is a prazosin analogue and a potent α1-adrenergic antagonist. 125I-A55453 is a high-affinity alpha 1-adrenergic receptor probe.

Metazosin (Kenosin) is a potent α1 adrenoceptor blocker. Metazosin is an antihypertensive agent lowering blood pressure.

Palmitoyl serinol (N-Palmitoyl serinol) is an analog of the endocannabinoid N-palmitoyl ethanolamine (PEA). Palmitoyl serinol improves the epidermal permeability barrier in both normal and inflamed skin.

Pregnenolone-d4-1 (3β-Hydroxy-5-pregnen-20-one-d4-1) is the deuterium labeled Pregnenolone. Pregnenolone (3β-Hydroxy-5-pregnen-20-one) is a powerful neurosteroid, the main precursor of various steroid hormones including steroid ketones. Pregnenolone acts as a signaling-specific inhibitor of cannabinoid CB1 receptor, inhibits the effects of tetrahydrocannabinol (THC) that are mediated by the CB1 receptors. Pregnenolone can protect the brain from cannabis intoxication. Pregnenolone is also a TRPM3 channel activator, and also can weakly activate TRPM1 channels.

CB65 is a potent and high affinity CB2 selective agonist with a Ki value of 3.3 nM. CB65 exhibits a Ki of >1000 nM for CB1 receptor.

Nemonapride is a highly potent dopamine D2 receptor antagonist with a Ki of 0.06 nM. Nemonapride also activates 5-HT1A receptor with an IC50 of 34 nM. Nemonapride is an antipsychotic that readily passes through the blood brain barrier and exhibits potent neuroleptic effects in animals.

Ropinirole (SKF 101468) is an orally active, potent D3/D2 receptor agonist with a Ki of 29 nM for D2 receptor. Ropinirole has pEC50s of 7.4, 8.4 and 6.8 for hD2, hD3 and hD4 receptors, respectively. Ropinirole has no affinity for the D1 receptors. Ropinirole has the potential for Parkinson's disease.

Dopamine D3 receptor ligand is a potent, selective and high affinity ligand for Dopamine D3 receptor with 89-fold selective for D3 over D2 (D3 Ki= 8 nM, D2 Ki= 715 nM).

BMS-193884 is a selective, orally active, and competitive ETA antagonist with 10000-fold greater affinity for the human ETA receptor (Ki=1.4 nM) than for the ETB receptor.

GLP-1R agonist 8 is a potent GLP-1R agonist with an EC50 of < 2 nM (WO2021219019A1, compound 129a).

GLP-1R agonist 7 is a potent GLP-1R agonist with an EC50 of 0.67 µM (WO2021244645A1, compound WXA001).

GLP-1R agonist 5 is a potent GLP-1R agonist with an EC50 of <10 nM (WO2021259309A1, compound 35).

GLP-1R agonist 6 is a potent GLP-1R agonist with an EC50 of 0.15 nM for human GLP-1R (WO2021249492A1, compound 005A or 005B).

BAY 1214784 is a potent, selective, and orally active antagonist of the human gonadotropin-releasing hormone receptor (hGnRH-R). BAY 1214784 is a spiroindoline derivative compound. BAY 1214784 effectively lowers plasma luteinizing hormone levels by up to 49%, at the same time being associated with low pharmacokinetic variability and good tolerability. BAY 1214784 has the potential for the research of uterine fibroids.

Roxatidine is an active metabolite of Roxatidine acetate hydrochloride, is a histamine H2-receptor antagonist. Roxatidine, an anti-ulcer agent, suppresses histamine release (thus inhibiting proton secretion) and inhibits the production of VEGF-1, an important marker of inflammation and angiogenesis. Anti-allergic inflammatory effect.

REV 5901 is a competitive and orally active antagonist of leukotriene receptor, with a Ki of 0.7 μM. REV 5901 is also a 5-lipoxygenase inhibitor. REV 5901 can be used for the research of asthma in which leukotriene release be involved.

BAY-u 9773 is a non-selective antagonist of the CysLT receptors (cysteinyl leukotrienes receptors) with about the same IC50 for CysLT1 and CysLT2. BAY-u9773 is used for the inhibition of LT responses.

VU0455691 is a potent, selective orthosteric M1 mAChR antagonist (pIC50=6.64; IC50=0.23 µM for hM1).

Heliosupine N-oxide, Heliosupin metabolite, inhibits muscarinic acetylcholine receptor (mAChR) with the IC50 of 350 μM. Heliosupine N-oxide is a pyrrolizidine alkaloid (PA).

McN-A-343 is a selective M1 muscarinic agonist that stimulates muscarinic transmission in sympathetic ganglia. McN-A-343 reduces inflammation and oxidative stress in an experimental model of ulcerative colitis.

(EC50=3 nM). hMC1R agonist 1 shows at least 300-fold selectivity for hMC1R over hMC3R (b>EC50=902 nM), hMC4R (b>EC50=915 nM), and hMC5R (b>EC50=>1000 nM). hMC1R agonist 1 has the potential for the therapeutic intervention of melanocortin family.

N-Acetyltryptamine is a partial agonist for melatonin receptors in the retina. N-Acetyltryptamine is also used for determination of serotonin N-acetyl transferase activity.

MNI137 is a potent and selective negative allosteric modulator for group II mGluRs. MNI137 has IC50s values of 8.3 and 12.6 nM for human and rat mGlu2 inhibition of glutamate-induced calcium mobilization.

Imnopitant dihydrochloride is a neurokinin NK1 receptor antagonist.

BIBP3226 is a potent and selective neuropeptide Y Y1 (NPY Y1) and neuropeptide FF (NPFF) receptor antagonist, with Kis of 1.1, 79, and 108 nM for rNPY Y1, hNPFF2, and rNPFF, respectively. BIBP3226 displays anxiogenic-like effect.

Y1R probe-1 (Compound 39) is a high-affinity fluorescence probe for the Neuropeptide Y Y1 Receptor. Y1R probe-1 has the potential for the research of cancer disease.

Acetyl tetrapeptide-15 is a synthetic peptide used in the cosmetics for sensitive skin. Acetyl tetrapeptide-15 is derived from endomorphin-2 (Tyr-Pro-Phe-Phe-NH2), a human μ-opioid agonist with selective anti-nociceptive effect. Acetyl tetrapeptide-15 reduces skin hyperreactivity producing inflammatory, chronic and neuropathic pain, by increasing the threshold of neuronal excitability in μ-opioid receptor via an endorphin-like pathway.

MRS2395, an dipivaloyl derivative, is a potent P2Y12 receptor antagonist. MRS2395 inhibits ADP-induced platelet activation with a Ki of 3.6 μM. MRS2395 inhibits cAMP induced by ADP in rat platelets in the presence of PGE1 with an IC50 of 7 µM. MRS2395 enhances platelet dense granule release in response to TRAP-6.

BW A868C, a hydantoin compound, is a BW245C structural analogue. BW A868C is a selective and potent competitive prostaglandin D2 (PGD2) antagonist. BW A868C has no effect on other prostaglandin receptors (IP, EP1, EP2, TP and FP).

SC-51322 is a potent and selective antagonist of prostaglandin E2 (PGE2) receptor (EP 1), with a pA2 of 8.1. SC-51322 has the pain-relieving effect.

8-Isoprostaglandin E2 (iPE2-III) is a member of the isoprostane class of prostanoids. 8-Isoprostaglandin E2 acts at the receptor for thromboxane A2 (the TP) in vivo to induce vasoconstriction and platelet aggregation. 8-Isoprostaglandin E2 enhances receptor-activated NFkappa B ligand (RANKL)-dependent osteoclastic potential of marrow hematopoietic precursors via the cAMP pathway.

11β-Prostaglandin E2 (11β-Dinoprostone), a Prostanoid derivative, inhibits [3H]PGE2 binding to hypothalamic membranes in the rat with a Ki of 53.3 nM.

Tetranor-PGDM is an abundant urinary metabolite reflects biosynthesis of prostaglandin D2.

Thielavin A is an inhibitor of prostaglandin biosynthesis produced by Thielavia terricola. Thielavin A specifically inhibits the conversion of arachidonic acid into prostaglandin H2. Thielavin A has no anti-inflammatory activity on intravenous injection or on oral administration.

Thielavin B is an inhibitor of prostaglandin biosynthesis produced by Thielavia terricola. Thielavin B effectively influences the prostaglandin E2 synthesis from the endoperoxide. Thielavin B is significantly effective on carrageenan-induced oedema of rats when administered intravenously.

Cicaprost (ZK 96480), an orally active prostacyclin (IP) analogue, is a selective IP receptor agonist. Cicaprost inhibits platelet aggregation in both in vitro and animal studies. Cicaprost inhibits the induction of cyclin A and activation of the cyclin A promoter in primary and established rodent aortic smooth muscle cells.

AGI-43192 is a potent inhibitor of methionine adenosyltransferase 2A (MAT2A). AGI-43192 is a potent, but limited brain-penetrant compound. AGI-43192 has the potential for exploring the effects of SAM modulation in the central nervous system (CNS) and research of cancer disease.

AGI-41998 is a potent inhibitor of methionine adenosyltransferase 2A (MAT2A). AGI-41998 is a brain-penetrant compound. AGI-41998 has the potential for exploring the effects of SAM modulation in the central nervous system (CNS) and research of cancer disease.

SB-611812 is a urotensin II receptor (UTR) antagonist with the potential in the treatment of cardiovascular disease.

H2L5186303 is a potent and selective LPA2 receptor (lysophosphatidic acid 2 receptor) antagonist with an IC50 of 9 nM.

S1P1 agonist 5 is a selective and orally active S1P1 agonist. S1P1 agonist 5 inhibits the lymphocyte egress from the lymphoid tissue to the peripheral blood. S1P1 agonist 5 has the potential for the research of multiple sclerosis (MS).

BMS-639623 is a potent and orally activeCCR3 antagonist with an IC50 of 0.3 nM. BMS-639623 picomolar inhibition potency against eosinophil chemotaxis (IC50=38 pM). BMS-639623 can be used for the research of asthma.

CCR8 antagonist 1 (compound 15) is a potente human CCR8 antagonist with a Ki of 1.6 nM.

Fuscin, a fungal metabolite, CCR5 receptor antagonist with anti-HIV effects. Fuscin is a respiration and oxidative phosphorylation inhibitor, and also a mitochondrial SH-dependent transport-linked functions inhibitor.

CXCR4 antagonist 3 (compound 12a) is a potent antagonist of CXCR4 with an IC50 of 11 nM. CXCR4 antagonist 3 is a congener of TIQ15. CXCR4 antagonist 3 demonstrates the best overall properties including CXCR4 antagonism, CYP 2D6 inhibition, metabolic stability, and permeability. CXCR4 antagonist 3 has the potential for the research of human immunodeficiency virus.

HF51116 is a potent antagonist of CXCR4. HF51116 strongly antagonizes SDF-1α-induced cell migration, calcium mobilization, and CXCR4 internalization. HF51116 inhibits HIV-1 infection via CXCR4. HF51116 has the potential for the research of HIV-1 infection, hematopoietic stem cell mobilization, and cancer metastasis.

CXCR4 antagonist 4 is a potent, orally active CXCR4 antagonist (IC50=24 nM) with diminished CYP 2D6 activity, improved PAMPA permeability, potent inhibition of human immunodeficiency virus entry (IC50=7 nM).

GSK1614343 is the potent antagonist of growth hormone secretagogues type 1a (GHS1a) receptors. GSK1614343 inhibits the calcium response induced by ghrelin with a pIC50 value of 7.90. GSK1614343 represents a useful tool to investigate the physiological relevance of the ghrelin system in rat models.

Deoxycholic acid-13C (Cholanoic acid-13C) is the 13C-labeled Deoxycholic acid. Deoxycholic acid is specifically responsible for activating the G protein-coupled bile acid receptor TGR5 that stimulates brown adipose tissue (BAT) thermogenic activity.

Cholic acid 7-sulfate (7-Sulfocholic acid), a metabolite of Cholic acid, is a Takeda G-protein receptor 5 (TGR5) agonist. Cholic acid 7-sulfate can increase Tgr5 expression and induce GLP-1 secretion.

TCS-OX2-29 (hydrochloride) is a potent, high affinities and selective orexin-2 receptor (OX2R) antagonist with an IC50 value of 40 nM and a pKI value of 7.5. TCS-OX2-29 displays ~250-fold selectivity for OX2 over OX1.

Desmopressin is a synthetic analogue of the antidiuretic hormone arginine vasopressin.

VUF11207 fumarate is a potent CXCR7 (ACKR3) agonist with EC50 of 1.6 nM, inducse recruitment of β-arrestin2 and subsequent internalization of CXCR7 in cells.

GSK3004774 (GSK-3004774) is a potent, nonabsorbable, gastrointestinally-restricted agonist agonist of calcium-sensing receptor (CaSR) with pEC50 of 7.3.

GSK598809 hydrochloride is a potent, selective, CNS penetrant and orally bioavailable dopamine D3 receptor antagonist with pKi of 8.9.

GSK598809 (GSK-598809) is a potent, selective, CNS penetrant and orally bioavailable dopamine D3 receptor antagonist with pKi of 8.9.

(–)-IHCH7041 is a potent, selective partial agonist at DRD2/3 and 5-HT1AR, EC50 of 1.38 nM in Gαi1–γ9 dissociation and 2.75 nM in β-arrestin2 recruitment assays, with negligible 5-HT2AR binding (>100-fold selectivity).(–)-IHCH7041 exhibits negligible affinities for a large number of tested GPCRs, ion channels and transporters (Ki>500 nM), good affinities for DRD2 and DRD3 (Ki=14.42 nM), and moderate binding to 5-HT1A (Ki=60.62 nM).(–)-IHCH7041 behaves as a partial agonist in both G-protein signaling and β-arrestin recruitment activities at DRD2, DRD3 and 5-HT1AR.(–)-IHCH7041 displayed potent antipsychotic activity and has antidepressant properties and reverses cognitive impairmentin mice.

(R)-LMI (H2N-R-Leu-Met-Ile-COOH) is a tripeptide analogue of corticotropin-releasing factor (CRF) and CRF antagonist targeting the N-domain of CRF1 receptor; (R)-LMI inhibits CRF-stimulated cAMP accumulation with IC50 of 1.7 uM. (R)-LMI inhibits the production of interleukins by adipocytes and the proliferation rate of RAW 264.7 cells.

(R,S′)-MNF is a bi-functional GPR55 inhibitor and biased β2 adrenergic agonist, inhibits proliferation of PDAC cell lines (IC50=0.11 uM, PANC-1 cells). (R,S′)-MNF is a biased β2-AR agonist that selectively signals through Gαs and does not recruit β-arrestin-2. (R,S′)-MNF attenuates pro-oncogenic signaling and cellular proliferation in PANC-1 cells. (R,S′)-MNF (1 uM) significantly decreased ERK phosphorylation stimulated by the GPR55 ligand O-1602, (R,S′)-MNF is an effective inhibitor of GPR55 internalization and signaling. (R,S′)-MNF (20-40 mg/Kg) reduces PANC-1 tumor growth in a mouse xenograft model.

A novel potent, nonpeptide CXCR4 antagonist with IC50 of 0.93 nM; induces increased and prolonged mobilization of murine HSPC compared to AMD3100.

A novel potent, selective, brain-penetrating, orally active CXCR4 antagonist with Ki of 3 nM; inhibits tumor growth alone, increases the antitumor effects of bevacizumab and sunitinib in preclinical models of human glioblastoma; reduces the expression of Nestin in vivo, reduces tumor cell proliferation and accelerates cancer stem cell differentiation in glioblastoma preclinical models.

A peptide hormone and neuropeptide that is released into the bloodstream as a hormone in response to stretching of the cervix and uterus during labor and with stimulation of the nipples from breastfeeding.

A peptide, non-selective melanocortin receptor agonist for treatment for female sexual dysfunction; selectively stimulates solicitational behaviors in the female rat, without affecting lordosis, pacing, or other sexual behaviors, does not cause generalized motor activation; a peptide analogue of α-MSH.

A potent, selective and orally bioavailable GPR119 agonist with EC50 of 4 nM, with good selectivity versus a battery of receptors, ion channels and enzymes; causes greater reductions in cumulative food intake and higher fed plasma GLP-1 and peptide tyrosine tyrosine levels and decreased plasma insulin and glucose-dependent insulinotropic polypeptide levels, when combined with metformin, in diet-induced obese mice.

A potent, selective CCR5 antagonist and HIV-1 entry inhibitor with pIC50 of 8.37 and 8.46 in HOS and PBL assays, respectively.

A potent, selective CCR5 antagonist and HIV-1 entry inhibitor.

A potent, selective, small molecule motilin receptor agonist with pEC50 of 7.9 (hMTL-R); displays selectivity over closely related human ghrelin acceptor (pEC50< 6.0) and no liabilities at the hERG channel; possesses highly excellent pharmacokinetic profiles in both rat and dog.

A potent, selective, small molecule motilin receptor agonist with pEC50 of 7.9 (hMTL-R); displays selectivity over closely related human ghrelin acceptor (pEC50< 6.0) and no liabilities at the hERG channel; possesses highly excellent pharmacokinetic profiles in both rat and dog.

A potent, small molecule CXCR2 inhibitor with IC50 of 26 nM and 30 nM for mCXCR2 and hCXCR2, respectively; inhibits the growth and metastatic potential pancreatic ductal adenocarcinoma, enhances sensitivity to anti-PD1 immunotherapy in vivo; chemical analog of AZD 5069.

A potent, stable cyclohexapeptide somatostatin mimic that exhibits unique high-affinity binding to human somatostatin receptors (pKi=8.2/9.0/9.1/<7.0/9.9 for sst1/2/3/4/5, respectively); effectively inhibits GHRH-induced growth hormone release in primary cultures of rat pituitary cells with IC50 of 0.4 nM, also potently suppresses GH secretion in rats.

AGH-107 is a potent, selective 5-HT7 receptor agonist with Ki of 6 nM and EC50 of 19 nM, 176-fold selectivity over 5-HT1AR.AGH-107 exhibited high selectivity over related CNS targets, high metabolic stability and low toxicity in HEK-293 and HepG2 cell cultures.

AGH-192 is a potent, selective, orally bioavailable 5-HT7 receptor agonist with Ki of 4 nM.AGH-192 displays excellent water solubility, high selectivity over related CNS targets, high metabolic stability, oral bioavailability and low cytotoxicity.AGH-192 could crosses blood-brain barrier to a high extent.AGH-192 alleviates the symptoms of neuropathic pain in a mouse model.

ALESIA is a specific sphingosine-1-phosphate receptor 3 (S1PR3)-G12-biased agonist and selectively induces G12 signal.ALESIA promotes nitric oxide production and oxidative stress.ALESIA selectively induces apoptosis in cancer cells because of low glucose levels.Intraperitoneal administration of ALESIA improved the survival of mice with peritoneally disseminated rhabdomyosarcoma.ALESIA (Anticancer Ligand Enhancing Starvation-induced Apoptosis) is a new anticancer compound for glucose starvation therapy.

AMD3451 is a specific, dual CXCR5/CXCR4 antagonist with antiviral activity against a wide variety of HIV-1 and HIV-2 (IC50=1.2 to 26.5 uM) in vitro.AMD3451 has antiviral activity against a wide variety of R5, R5/X4, and X4 strains if HIV-1 and HIV-2 in various T-cell lines, CCR5- or CXCR4-transfected cells, PBMCs, and monocytes/macrophages.AMD3451 inhibited R5, R5/X4, and X4 HIV-1 primary clinical isolates in PBMCs (IC50, 1.8 to 7.3 uM), AMD3451 blocks R5 and X4 HIV-1 infection at the virus entry stage.AMD3451 dose-dependently inhibited the intracellular Ca2+ signaling induced by the CXCR4 ligand CXCL12 in T-lymphocytic cells and in CXCR4-transfected cells, as well as the Ca2+ flux induced by the CCR5 ligands CCL5, CCL3, and CCL4 in CCR5-transfected cells.AMD3451 did not interfere with chemokine-induced Ca2+ signaling through CCR1, CCR2, CCR3, CCR4, CCR6, CCR9, or CXCR3 and did not induce intracellular Ca2+ signaling by itself at 400 uM.AMD3451 inhibited CXCL12- and CCL3L1-induced endocytosis in CXCR4- and CCR5-transfected cells.AMD3451 does not inhibit the binding of CXCR4- or CCR5-specific MAbs.

ASP2205 (ASP2205 fumarate) is a potent, selective 5-HT2C receptor agonist with EC50 of 0.85/2.5 nM for human/rat 5-HT2C in the intracellular Ca2+ mobilization assays, respectively.ASP2205 showed partial agonistic action on human 5-HT2A receptor with EC50 of 96 nM, no agonistic action against 5-HT2B.ASP2205 (0.1-1 mg/kg, i.d.) significantly elevated the leak point pressure (LPP) in anesthetized rats in a dose-dependent manner.ASP2205 is a more potent and selective 5-HT2C receptor agonist than lorcaserin.

ASP8302 (ASP 8302) is a potent, selective, positive allosteric modulator (PAM) of muscarinic M3 receptor.Threonine 230 (Thr 230) is the amino acid essential for the PAM effect of ASP8302.

AstraZeneca CCR4 antagonist is a potent, selective CCR4 antagonist, inhibits CCR4 ligand macrophage-derived chemokine (MDC/CCL22) in CCR4+CD4+ T cells.

BL-6020/979 (SNT207979) is an orally available, selective, potent MC4R antagonist with IC50 of 19 nM; weakly binds to MC-3 and MC-5 receptors with IC50 of 2.7 uM and 0.89 uM, respectively, >10,000-fold selectivity over MC-1R; demonstrates in animal models and presents a promising candidate suitable for further development towards a first-in-class treatment option for cachexia.

BMS-570520 is a potent, selective CCR3 antagonist with IC50 of 1.9 nM, inhibits eotaxin-induced chemotaxis with IC50 of 0.068 nM.BMS-570520 displays reduced inhibition on CYP2D6 (IC50=1300 nM) compared with DPC168 (IC50=30 nM), also possesses >100-fold selectivity over 5-HT2a, DAT and NET.BMS-570520 showed good activity in murine models of CCR3 antagonism and greater in vitro potency and in vivo in the mouse intranasal eotaxin challenge mode.

BMS-846372 (BMS846372) is a potent, selective, orally active CGRP receptor antagonist with Ki of 0.07 nM (hCGRP).BMS-846372 inhibited CGRP-stimulated cAMP production in SK-N-MC cells with IC50 of 0.22 nM, could completely inhibited CGRP-mediated elevation of cAMP.BMS-846372 showed exposure-dependent inhibition of CGRP-induced increases in marmoset facial blood flow upon subcutaneous (sc) dosing in hαCGRP-induced increases in facial blood flow model.

BPR1M97 is a dual-acting mu-opioid receptor (MOP) and nociceptin-orphanin FQ peptide (NOP) receptor agonist with Ki values of 1.8 and 4.2 nM, respectively.BPR1M97 elicited full agonist properties for all cell-based assays tested in MOP-expressing cells.BPR1M97 acted as a G protein-biased agonist for NOP.BPR1M97 initiated faster antinociceptive effects after subcutaneous injection and elicited better analgesia in cancer-induced pain than morphine.BPR1M97 caused less respiratory, cardiovascular, and gastrointestinal dysfunction, compared with morphine.

BX471 is a potent, selective, orally available CCR1 antagonist with Ki of 1 nM for hCCR1, displays 100 times less affinity for rat CCR1; shows 10,000-fold selectivity for CCR1 compared with 28 GPCRs (); displays CCR1 ligands MIP-1α, RANTES, and MCP-3 with high affinity (Ki=1-5.5 nM), inhibits a number of CCR1-mediated effects including Ca(2+) mobilization, increase in extracellular acidification rate, CD11b expression; effectively reduces disease in a rat experimental allergic encephalomyelitis model of multiple sclerosis.

CCR2 covalent-IN-14 is a covalent, negative allosteric modulator (NAM) of CCR2, binds to intracellularly pocket of CCR2 with Ki of 4 nM.CCR2 covalent-IN-14 is more potent than non-covalent analogue and wash-resistant in functional assays (IC50=33 nM in GTPγS binding assay on U2OS-CCR2 cell membranes, IC50=4 nM in β-arrestin recruitment assays).CCR2 covalent-IN-14 displays little to no inhibitory potency on CCR1 and CCR5.The affinity of CCR2 covalent-IN-14 for both the C70S and C75S CCR2 mutants is significantly decreased compared to WT CCR2.

CCR2 inhibitor SD-24 is a potent selective CCR2 antagonist with pKi of 8.5.

CCR4-IN-38 (CCR4-351) is a potent, selective, orally bioavailable CCR4 antagonist with IC50 of 50 nM (Chemotaxis inhibition).CCR4-IN-38 inhibits the recruitment of Treg into the tumor microenvironment (TME).CCR4-IN-38 elicits antitumor responses as a single agent or in combination with an immune checkpoint blockade.

CCR7 inhibitor Cmp1205 is an allosteric ligand and antagonist for human CC chemokine receptor 7 (CCR7) with Kd of 3 nM, suppresses arrestin binding in response to activation by CCL19 with IC50 of 7.3 uM.Cmp1205 binds to a pocket at the intracellular part of CCR7 between the ends of TM1, TM2, TM3, and TM6 and the loop between TM7 and H8.Cmp1205 allosterically inhibits binding of the native chemokine CCL19 ligand in a membrane-based competition binding experiment with IC50 of 35 nM.

CCX-6239 is a novel potent, orally available CCR4 inhibitor with potential utility in the treatment of allergic airways disease.

CJ-1639 (CJ1639) is a potent, highly selective dopamine D3 receptor (D3R) full agonist with Ki of 0.5 nM, >5,000-fold selectivity over D1 and D2 receptors in binding assays.CJ-1639 binds to human D3 receptor with a K(i) value of 3.61 nM and displays over >1000-fold selectivity over human D1 and D2 receptors.CJ-1639 is an excellent pharmacological tool to elucidate the role of the D3 receptor in different neurological conditions in animal models.

Cotadutide (MEDI-0382) is a dual GLP-1/glucagon receptor peptide agonist with robust anti-obesity and metabolic effects.

CXCR6 inhibitor 81 is a potent (EC50=40 nM) and selective orally bioavailable small molecule antagonist of human CXCR6 receptor; Compound 81 displays >10-fold improvement in potency in both the β-arrestin and cAMP assays (IC50 =40 and 540 nM, respectively) compared to ML339. CXCR6 inhibitor 81 inhibits migration of SK-HEP-1 hepatoma cells in a dose dependent manner. Compound 81 has promising oral DMPK data, significantly decreases tumor growth in a 30-day mouse xenograft model of HCC.

CXCR7 modulator 20 is a small molecule modulator of the atypical chemokine receptor CXCR7 with Ki of 52 nM.

DA-1241 (DA1241) is a novel potent, highly selective GPR119 agonist, activates human GPR119 (EC50=4.37 nM) in increasing cAMP levels in GPR119-overexpressing HEK293 cells.DA-1241 increased cAMP levels via activated mouse GPR119 (EC50, 71.5 nM) and rat GPR119 (EC50, 156 nM).DA-1241 showed no significant activity against 156 off-target proteins at 10 uM, including human GLP-1 receptor and human GPR40.DA-1241 stimulated insulin secretion in hamster insulinoma HIT-T15 cells with EC50 of 22.3 nM, association with enhanced human insulin promoter activity.DA-1241 significantly reduced postprandial glucose excursion, significantly preserved β-cell mass with reduced PDX1 levels in the islets from HFD/STZ diabetic mice.DA-1241 reduced triglyceride content in the liver thereby improved fatty liver, reduced gluconeogenic enzyme expression in HepG2 cells and mouse liver, reduced autophagic flow in HepG2 cells.

DCP1-3 is a novel allosteric ligand of the angiotensin receptor AT1R, displays NAM potency on AngIV with IC50 of 0.29 uM.DCP1-3 reduces AngII-induced contraction in renal and iliac arteries in mice.DCP1-3 inhibits IgG binding to HEK-AT1R cells with IC50 of 2.9 nM.DCP1-3 reverses PAM effect of the IgG on the agonist-induced calcium response.

DL-175 is a potent and selective biased GPR84 agonist with EC50 of 33 nM.DL-175 exhibits no significant activity in a panel of 168 other GPCRs.DL-175 display significantly biased signaling across GPR84-overexpressing cells, primary murine macrophages, and human U937 cells.DL-175 markedly different abilities to induce chemotaxis in human myeloid cells, while causing similar levels of phagocytosis enhancement.

DPC168 (DPC-168) is a highly potent, selective CC chemokine receptor-3 (CCR3) antagonist with IC50 of 2.0 nM, inhibits eotaxin-induced chemotaxis with IC50 of 0.034 nM.DPC168 demonstrates potency for mouse CCR3 (chemotaxis IC50=41 nM) and oral bioavailability in mice (20% F).DPC168 reduced eosinophil recruitment into the lungs in a dose-dependent manner in these animal models.

EMU-116 (EMU-000116) is a potent, selective CXCR4 antagonist with IC50 29.6 nM in Ca2+ flux assay.

Enerisant (S091,TS-091) is a potent, selective histamine H3 receptor antagonist/inverse agonist with IC50 of 2.89 and 14.5 nM against hH3R and rH3R, respectively.Enerisant inhibited R-α-methylhistamine–stimulated [35S]GTPγS binding to human histamine H3 receptor and rat histamine H3 receptor with IC50 values of 1.06 and 10.05 nM, respectively, inhibited basal [35S]GTPγS binding to human histamine H3 receptor with an EC50 value of 0.357 nM.Enerisant displays negligible effects on binding to human histamine H1, H2, and H4 receptor subtypes, as well as negligible affinities for 66 other receptors, transporters, and ion channels at 1-10 uM.Oral administration of enerisant hydrochloride attenuated the dipsogenia response on R-α-methylhistamine–induced dipsogenia in rats, the intraperitoneal administration of enerisant hydrochloride increased the total extracellular acetylcholine levels in the mPFC.Enerisant hydrochloride significantly decreased slow-wave deep sleep at doses of 1-10 mg/kg (P < 0.01-0.05). Enerisant hydrochloride (1, 3 and 10 mg/kg, p.o.) did not affect the accumulated locomotor activity time at up to 7 hours after administration.

Enerisant hydrochloride (TS091 hydrochloride) is a potent, selective histamine H3 receptor antagonist/inverse agonist with IC50 of 2.89 and 14.5 nM against hH3R and rH3R, respectively.Enerisant inhibited R-α-methylhistamine–stimulated [35S]GTPγS binding to human histamine H3 receptor and rat histamine H3 receptor with IC50 values of 1.06 and 10.05 nM, respectively, inhibited basal [35S]GTPγS binding to human histamine H3 receptor with an EC50 value of 0.357 nM.Enerisant displays negligible effects on binding to human histamine H1, H2, and H4 receptor subtypes, as well as negligible affinities for 66 other receptors, transporters, and ion channels at 1-10 uM.Oral administration of enerisant hydrochloride attenuated the dipsogenia response on R-α-methylhistamine–induced dipsogenia in rats, the intraperitoneal administration of enerisant hydrochloride increased the total extracellular acetylcholine levels in the mPFC.Enerisant hydrochloride significantly decreased slow-wave deep sleep at doses of 1-10 mg/kg (P < 0.01-0.05). Enerisant hydrochloride (1, 3 and 10 mg/kg, p.o.) did not affect the accumulated locomotor activity time at up to 7 hours after administration.

ENMD-1068 is a novel selective PAR2 antagonist without inhibitory activity against thrombin-mediated PAR3 and PAR4 signaling; blocks TNFα production in synovial explants from patients with arthritis, and inhibits mast cell tryptase-induced recruitment of eosinophils into the pleural cavity of mice, dose dependently attenuates joint inflammation.

FE 205030 (FE205030) is a potent, selective peptidic CGRP antagonist with IC50 of 0.2 nM.FE 205030 displays>100,000 fold against hAM1R and >6363 fold against hAM2R tested in Human CGRP, AM1R and AM2R receptor cAMP assays.FE 205030 inhibited CGRP-induced vasodilation in isolated human mesenteric resistance arteries in an ex vivo isometric myograph study; effectively blocked CGRP-induced vasodilation with a pA2 of 9.3.FE 205030 is a first in class injectable fast acting selective and potent agent for the treatment of acute episodic migraine.

FFA2R agonist 58 is a potent, allosteric FFAR2 (GPR43) agonist/modulator.FFA2R agonist 58 functions as a positive/priming modulator in these cells by turning the natural FFA2R agonist acetate into a potent activator of the neutrophil NADPH-oxidase.FFA2R agonist 58 lowers the concentration of acetate required to induce a transient rise in the concentration of intracellular Ca2+ in neutrophils, has no direct effect on the neutrophil NADPH-oxidase activity but affects the response induced by acetate.FFA2R agonist 58 significantly reduced the amount of internalized influenza A virus (IAV) in treated A549 cells.

Firazorexton is a potent, selective, experimental orexin 2 receptor (OX2R) agonist.

FLX-475 is a novel CCR4 antagonist for the treatment of cancer.

GnRH antagonist 2 is a GnRH receptor antagonist that can be used for endometriosis research.

GPR183 antagonist SAE-14 is a potent, selective GPR183 antagonist with IC50 of 28.5 nM, inhibits GPR183-dependent 7α,25-dihydroxycholesterol-induced calcium signaling in HL-60 cells.GPR183 antagonist SAE-14 inhibits calcium mobilization induced by 7α,25-OHC (EC80 209 nM).GPR183 antagonist SAE-14 reversed CCI-induced mechanical allodynia in a time-dependent manner when administered in vivo to mice.7α,25-dihydroxycholesterol induced allodynia in mice, SAE-14 blocked the effects of 7α,25-OHC in a dose-dependent manner.

GPR183 antagonist SAE-14 is a potent, selective GPR183 antagonist with IC50 of 8.3 nM, inhibits calcium mobilization induced by 7α,25-OHC in HL-60 cells.

GR-127935 is a potent and selective 5-HT1B/1D receptor antagonist with pKi of 8.5 for both guinea pig 5-HT1D and rat 5-HT1B receptor; displays >100-fold selectivity over 5HT1A, 5-HT2A, 5-HT2C receptors and other receptor types; blocks porcine carotid vascular response to sumatriptan in vivo; orally bioavailable and centrally active.

GSK1034702 (GSK-1034702) is a potent, allosteric M1 receptor agonist, inhibits binding of [3H]-NMS (0.5 nM) to M1 mAChR with pKi of 6.5; improves memory encoding potentially by modulating hippocampal function.

GSK-1842799 is a potent, selective, oral bioavailable S1P1 agonist with bind affinity of 0.52 nM; displays an excellent selectivity (>3,000-fold) for S1P1 over S1P3; significantly reduces blood lymphocyte at 3 mg/kg, achieves efficacy equivalent to FTY720 in the mouse EAE model of MS.

GSK-2239633 is a potent, selective, allosteric CCR4 antagonist with pIC50 of 7.96; also inhibits TARC-induced increases in the F-actin content of isolated human CD4+ CCR4+ T-cells with pA2 of 7.1.

GSK-588045 is a potent and selective 5-HT1A/B/D receptor antagonist with Ki of 9.5/8.8/9.8, respectively; exhibits high selectivity over human hERG potassium channels, favorable pharmacokinetics, and excellent activity in vivo in rodent pharmacodynamic (PD) models; demonstrates potential as a faster acting antidepressant/anxiolytic with reduced side-effect burden.

GSK812397 is a potent, selective, noncompetitive, orally available antagonist of CXCR4 receptor, inhibits entry of X4-tropic strains of HIV-1 with IC50 of 4.60 nM and 1.50 nM in PBMCs and HOS assays, respectively; does not block CCR5-mediated viral entry in the R5 viral HOS assay (IC50>25 uM); produces a concentration-dependent decrease in both an SDF-1-mediated chemotaxis and intracellular calcium release (IC50=0.34 nM and 2.41 nM, respectively) in cell-based functional assays; demonstrates antiviral activity against a broad range of X4-utilizing strains of HIV-1.

HF50731 (HF-50731) is a novel potent, selective CXCR4 antagonist with Ki of 19.8 nM in the CXCR4 competitive binding assay.HF50731 significantly inhibited SDF-1α-induced calcium mobilization (IC50=621 nM) and cell migration, and blocked HIV-1 infection via antagonizing CXCR4 coreceptor function (IC50=1.5 uM).The structure-activity relationship analysis demonstrated that HF50731 could primarily occupy the minor subpocket of CXCR4 and partially bind in the major subpocket by interacting with residues W94, D97, D171, and E288.

HL-43 (EP4 antagonist HL-43) is a selective prostaglandin E receptor 4 (EP4) antagonist, promotes chondrocyte differentiation/cartilage regeneration and anabolism with low toxicity; HL-43 exhibits the highest potency in inducing Col2a1 expression and reducing Mmp3 expression in presence of IL-1β. HL-43 downregulats Mmp3/13 expression in a dose-dependent manner. HL-43 induces anabolic factors (ACAN and SOX9), and suppresses catabolic factor (MMP13), and hypertrophic marker (COLX), inhibits the STAT3 catabolic pathway;. HL-43 promotes chondrocyte differentiation and ECM generation, and inhibits matrix degradation in both human and mouse articular cartilage explants. HL-43 enhances cartilage repair and regeneration in different artilage defect (CD) animal models.

I-287 is a potent, selective, orally active inhibitor of PAR2, negative PAR2 allosteric modulator, inhibits PAR2-mediated activation of Gq and G12/13 but not Gi/o proteins (IC50=45-390 nM); I-287 is a negative allosteric modulator (NAM) and not an orthosteric competitive antagonist of hPAR2. I-287 inhibits PAR2-mediated activation of DAG/Ca2+/PKC and RhoA/SRF-RE, as well as FAK and ERK1/2 signaling pathways, shows no effect on PAR2-mediated recruitment of βarrestin2 and receptor internalization. I-287 inhibits PAR2-induced secretion of IL-8 cytokine in vitro and reduces Freund's adjuvant (CFA)-induced paw edema model in mice.

Inupadenant (EOS-850, EOS100850) is a non brain-penetrant, potent and highly selective small molecule antagonist of adenosine A2a receptor (A2AR), shows activity at the high adenosine concentrations found in tumors.

IS811 is a potent, selective CCR3 antagonist with IC50 of 2.0 nM, potently inhibits chemotaxis with EC50 of 19 nM.IS811 displays >100-fold selectivity over 5-HT2a, DAT and NET.IS811 (0-20 mg/kg) dose-dependently inhibited eotaxin-induced eosinophil influx to the lung in vivo.

KARI 201 (KARI-201) is a dual-action small molecule that exhibit highly selective inhibition effects on Acid sphingomyelinase (ASM), and act as a ghrelin receptor agonist.KARI 201 is a competitive inhibitor that binds to the active site of ASM.Incorporation of KARI 201 into ASM was decreased with increasing concentrations of sphingomyelin, yielding KM values of 332.5, 433.9, and 572.6 μM at 1, 10, and 100 μM KARI 201, respectively.Administration of KARI 201 reduces amyloid pathology and restores cognitive impairment in APP/PS1 mice.KARI 201 ameliorates defective autophagy degradation by regulating lysosomal biogenesis in neurons.KARI 201 is a ghrelin receptor agonist and improves hippocampal neurogenesis and synapse plasticity.

Lazucirnon (KST4290, ALK4290) is a small molecule, orally active inhibitor against CCR3, the natural receptor for chemokine eotaxin, decreases inflammatory cytokines in preclinical models.Lazucirnon (KST4290, ALK4290) blocks eotaxin from binding to its G-protein coupled receptor (GPCR) CCR3.CCR3 plays an important modulatory role in inflammation, immune cell recruitment, and neovascularization, processes important for the pathogenesis of wet age-related macular degeneration (wet AMD) and other neurological and immunological diseases.

LSN3172176 is a novel potent, selectiive M1 mAChR partial agonist (EC50 2.4-7.0nM, Emax 43%-73%), shows binding selectivity for M1 mAChRs (Kd=1.5 nM); LSN3172176 is a potential PET tracer for assessment of M1 mAChR target engagement in the clinic and to further elucidate the function of M1 mAChRs in health and disease.

LY-3502970 (Orforglipron) is a potent, selective, orally active non-peptide agonist of glucagon-like peptide-1 (GLP-1) receptor.LY3502970 is a partial agonist, biased toward G protein activation over β-arrestin recruitment at the GLP-1R.

MK-8666 is a selective partial GPR40 agonist developed for the treatment of type 2 diabetes mellitus.

ML 339 is a potent and selective hCXCR6 antagonist (IC50 = 140 nM), 100-fold less active at the murine CXCR6 receptor (IC50 = 18 uM); ML 339 exhibits selectivity over CXCR5, CXCR4, CCR6 and APJ receptors.

ML381 (VU0488130) is a highly mAChR subtype selective M5 orthosteric antagonist with IC50/Ki of 450/340 nM for hM5, has no inhibitory activity on hM1-4 (IC50>30 uM); exhibits good DMPK properties and CNS penetration (B:P ratio of 0.58) to support both in vitro and in vivo studies.

N8279 (NCATS-SM8864) is a selective, brain-penetrant small molecule Gαq-biased GHSR1a agonist with binding IC50 of 1.3 uM.N8279 is nearly an order of magnitude (8.9-fold) more potent than the endogenous ligand ghrelin and is a full agonist.iCa2+ EC50 of N8279 is 41-fold more potent than its GHSR1a binding IC50, suggesting possible allosteric activity, which could be competitively inhibited by GHSR1a antagonists YIL781 and JMV2959.N8279 is a weak activator of GHSR1a-mediated, βarr2-dependent cellular responses relative to ghrelin.N8279 requires receptor sites and/or conformational states driven by the GHSR1a ECD that are distinct from ghrelin.N8279 is brain-penetrant and attenuates aberrant DAergic behavior in mice.

NLX-204 is a potent and selective ERK1/2 phosphorylation-preferring serotonin 5 HT1A receptor agonist with pKi = 10.19. NLX-204 displayed high selectivity in the SafetyScreen44 panel (including hERG channel), high solubility, metabolic stability, and Caco-2 penetration and did not block CYP3A4, CYP2D6 isoenzymes, or P-glycoprotein. Preliminary in vivo studies confirmed its promising pharmacokinetic profile. NLX-204 also robustly stimulated ERK1/2 phosphorylation in rat cortex and showed highly potent (MED = 0.16 mg/kg) and efficacious antidepressant-like activity, totally eliminating immobility in the rat Porsolt test.

ONO-8055 is a highly selective and potent EP2/EP3 dual agonist with EC50 of 0.67/0.7 nM, shows >450-fold selectivity over EP4 receptors (EC50=339 nM); improves the lower urinary tract dysfunctions of neurogenic UAB in a rat lumber spinal canal stenosis model with twice-daily (bid) oral dosing of 0.01 mg/kg, demonstrates much higher in vivo efficacy than the currently used drug for UAB.

OX2R agonist 1 is a potent, selective, small-molecule agonist of orexin receptor 2 (OX2R) with pEC50 of 8.28, >300-fold selectivity over OX1R.

PAR2 antagonist C391 (C391) is a selective PAR2 antagonist, potently inhibits peptidomimetic-induced PAR2 Ca2+ signalling with IC50 of 1.3 uM.C391 blocks both PAR2 Ca2+ and MAPK signalling pathways activated by peptidomimetics and/or proteinase activation.C391 effectively attenuated compound 48/80-induced thermal hyperalgesia in vivo.C391 blocked A. alternata-induced, PAR2-dependent Ca2+ and MAPK signalling in 16HBE14o- cells, as well as β-arrestin recruitment in HEK 293 cells.C391 effectively attenuated A. alternata-induced inflammation, mucus production, mucus cell hyperplasia and airway hyperresponsiveness in acute allergen-challenged murine models.

PBI-4547 is an agonist of GPR40/120 and an antagonist of GPR84, also is a partial ligand and activator of PPAR.PBI-4547 dose-dependently inhibits GPR84/Gαi2 activation (reflected by an increase in BRET signal) with IC50 of 17 uM, activates GPR40 (EC50 of 102 µM for Gαq and 16 µM for Gαi2) and dose-dependently promoted β-arrestin-2 recruitment to GPR120 (EC50=148 uM).PBI-4547 prevents progression, improves glucose metabolism in a mouse model of NAFLD, restores hepatic glucose and FA metabolism.

PF-06669571 (PF 6669571) is a novel dopamine D1 receptor (D1R) partial agonist with Ki of 10 nM, demonstrates efficacy in pre-clinical models of Parkinson’s disease symptoms.

PSB-1584 is a potent, selective agonist of GPR84 with EC50 of 5.0 nM, β-arrestin IC50 of 3.2 nM in human GPR84-expressing cells.

PSB-16671 is a novel orthosteric and allosteric activator of GPR84, activates human GPR84 with EC50 of 41.3 nM in cAMP accumulation assays. PSB-16671 is selective versus related fatty acid receptors and the arylhydrocarbon receptor. PSB-16671 shows an EC50 of 5.47 uM in β-Arrestin assays, and allosteric KB value of 634 nM.

PSB-17365 is a potent, selective, Gi-biased agonist of GPR84 with EC50 of 2.5 nM, β-arrestin IC50 of 104 nM in human GPR84-expressing cells.

PZ-1361 is a potent and selective 5-HT7 receptor antagonist with Ki of 33 nM, exhibit significant in vivo antidepressant and pro-cognitive properties in rodents.

R995045 is a novel δ-opioid receptor (δOR) agonist with pKi of 5.94, cAMP pIC50 of 6.01, >10-fold selectivity over µOR and κOR.R995045 acts as a negative allosteric modulator for leu-enkephalin potency in the cAMP glosensor assay.

RS-1269 is a highly potent, selective CCR4 antagonist, inhibits [125I]CCL17 binding to human CCR4 with IC50 of 27.7 nM.RS-1269 also has strong affinity to displace the CCL17 binding with IC50 of 27.0 nM in CCR4-expressing CHO cells.RS-1269 displays no competitive displacement in the binding of [125I]CCL3 (MIP-1α) to CCR1 and [125I]CCL2 (MCP-1) to CCR2b.RS-1269 dose-dependently inhibited CCL17-induced migration of Th2 cells with IC50 of 5.5 nM.Orally administered RS-1269 (30 mg/kg) ameliorates ovalbumin-induced ear swelling in mice.RS-1269 also inhibited LPS-induced TNF-α production in vivo.

RS-1748 is a highly potent, selective, orallu active CCR4 antagonist, inhibits [125I]CCL17 binding to human CCR4 with IC50 of 59.9 nM.RS-1748 displays no competitive displacement in the binding of [125I]CCL3 (MIP-1α) to CCR1 and [125I]CCL2 (MCP-1) to CCR2b. dose-dependently inhibited 50 nM CCL22-induced [Ca2+]i mobilization with IC50 of 28.3 nM, inhibited the binding of [35S]GTPgS to human CCR4-expressing CHO cells with IC50 of 18.4 nM.Orally administered RS-1748 (30 mg/kg) significantly lowered the total cell numbers and the eosinophils numbers in ovalbumin-sensitized guinea pigs.

RTI-7470-44 is a potent, selective human trace amine-associated receptor subtype 1 (hTAAR1) antagonist with IC50 of 8.4 nM in vitro cAMP functional assay.RTI-7470-44 exhibits a Ki of 0.3 nM in a radioligand binding assay, and shows species selectivity (>90-fold) for hTAAR1 over the rat and mouse orthologues.RTI-7470-44 displays good blood–brain barrier permeability, moderate metabolic stability, and a favorable preliminary off-target profile.RTI-7470-44 increased the spontaneous firing rate of mouse VTA dopaminergic neurons and blocked the effects of the known TAAR1 agonist RO5166017.

RTICBM-229 is a potent, selective, brain-penetrant CB1 negative allosteric modulator (NAM) with IC50 of 169 nM in Ca2+ assay, 40 nM in GTPγS assay.

RTICBM-74 is a potent, selective, brain-penetrant CB1 negative allosteric modulator (NAM) with IC50 of 23 nM in Ca2+ assays.RTICBM-74 displays excellent half-life and low clearance against rat liver microsomes and hepatocytes, and excellent brain penetrance in rats.RTICBM-74 specifically reduces alcohol intake across a range of doses in male or female Wistar or Long-Evans rats, reduces alcohol intake and does not affect locomotion or sucrose self-administration.

S1P5-IN-15 is a potent, selective, orally active and brain-penetrant S1P5 antagonist with IC50 of 0.1 nM, no effect on S1P1-4.

SX-682 (SX682) is a potent, allosteric, orally bioavailable inhibitor of CXCR1 and CXCR2.SX-682 enhances tumor infiltration, activation, and the therapeutic efficacy of adoptively transferred NK cells.SX-682 significantly inhibits trafficking of PMN-MDSCs without altering CXCR2 ligand expression.SX-682 enhances T cell-based immunotherapeutic efficacy.

TAK-925 (Danavorexton) is a potent, selective, and brain-penetrant Orexin 2 receptor (OX2R) agonist with EC50 of 5.5 nM, no significant inhibition on OX1R (IC50>100 uM).TAK-925 also showed good selectivity against 106 off-target enzymes and receptors.

TASP0410461 is a potent, selective histamine H3 receptor antagonist/inverse agonist.

TG8-260 is a second-generation, potent, selective EP2 antagonist with Schild KB of 13.2 nM.TG8-260 displays 500-fold selectivity to EP2 against other prostanoid receptors.TG8-260 has a plasma half-life of 2.14 h (PO) and excellent oral bioavailability (77.3%), TG8-260 is a potent inhibitor of CYP450 enzymes.TG8-260 displays antagonistic activity on the induction of EP2 receptor-mediated inflammatory gene expression in microglia BV2-hEP2 cells.TG8-260 reduces hippocampal neuroinflammation and gliosis after pilocarpine-induced status epilepticus in rats.TG8-260 is a tool for investigating anti-inflammatory pathways in peripheral inflammatory disease animal models.

TPN672 (TPN 672) a novel antipsychotic compound with high affinity for serotonin and dopamine receptors 5-HT1AR, (Ki=0.23 nM), 5-HT2AR (Ki=2.58 nM) as well as moderate affinity for D3R (Ki=11.55 nM) and D2R (Ki=17.91 nM).TPN672 acted as a potent 5-HT1AR agonist, D2R/D3R partial agonist, and 5-HT2AR antagonist in vitro functional assays.TPN672 displayed robust antipsychotic efficacy in rodent models (e.g., blocking phencyclidine-induced hyperactivity), significantly better than aripiprazole, and ameliorated negative symptoms and cognitive deficits in the sociability test, dark avoidance response, Morris water maze test, and novel object recognition test.

TT-OAD2 hydrochloride is a potent, selective, non-peptide agonist of glucagon-like peptide-1 (GLP-1) receptor with EC50 of 5 nM.TT-OAD2 inhibited GLP-1- and oxyntomodulin-mediated cAMP, calcium, pERK1/2 and β-arrestin responses in a concentration-dependent manner.TT-OAD2 exhibits biased agonism, and kinetics of G-protein activation and signalling that are distinct from peptide agonists.

TT-OAD2 is a potent, selective, non-peptide agonist of glucagon-like peptide-1 (GLP-1) receptor with EC50 of 5 nM.TT-OAD2 inhibited GLP-1- and oxyntomodulin-mediated cAMP, calcium, pERK1/2 and β-arrestin responses in a concentration-dependent manner.TT-OAD2 exhibits biased agonism, and kinetics of G-protein activation and signalling that are distinct from peptide agonists.

Ulotaront (SEP-363856, SEP-856) is a novel psychotropic agent with agonism at trace amine receptor 1 (TAAR1) and 5-HT1A receptors but no appreciable action at dopamine D2 receptors.Ulotaront significantly reduced the ketamine-induced increase in dopamine synthesis capacity.

V-0219 is a small molecule positive allosteric modulator (PAM) of GLP-1R with Emax of 60% in the cAMP assay.V-0219 potentiated insulin secretion in INS-1 β-cells with EC50 of 0.25 nM, the best response was observed at 0.1 nM, when a fixed concentration of 0.2 nM of GLP-1 was added to the dose-response curve of 9, the maximal response observed reached a plateau at 0.1 nM, with an EC50 value of 0.008 nM.V-0219 shows a remarkable in vivo activity, reducing food intake and improving glucose handling in normal and diabetic rodents.

Vercirnon (GSK1605786A, CCX282-B) is a potent, selective, orally bioavailable antagonist of CCR9, inhibits CCR9-mediated Ca2+ mobilization and chemotaxis on Molt-4 cells with IC50 of 5.4 and 3.4 nM, respectively.Vercirnon (GSK1605786A, CCX282-B) displays high selectivity for CCR9 over CCR1-12 and CX3CR1-7 (IC50>10 uM).Vercirnon (GSK1605786A, CCX282-B) is an equipotent inhibitor of CCL25-directed chemotaxis of both splice forms of CCR9 (CCR9A and CCR9B) with IC50 values of 2.8 and 2.6 nM, respectively.CCX282-B also inhibited mouse and rat CCR9-mediated chemotaxis.Inhibition of CCR9 with CCX282-B results in normalization of Crohn's disease such as histopathology associated with the TNF(ΔARE) mice.

VISTA inhibitor M351-056 is a small molecule compound having affinity with VISTA.

Vornorexant (TS-142, ORN0829) is a potent dual orexin 1 and 2 receptor antagonist with IC50 of 1.05 and 1.27 nM for hOX1R and hOX2R, resepctively.Vornorexant (TS-142, ORN0829) exhibited potent sleep-promoting effects at a po dose of 1 mg/kg in a rat polysomnogram study.Vornorexant (TS-142, ORN0829) is a viable candidate and is currently in clinical development for the treatment of insomnia.

VU6007215 is a potent, selective M4 positive allosteric modulator (PAM) with EC50 of 144 nM (hM4) and 295 nM (rM4).

VU6009048 is a potent, selective M4 positive allosteric modulator (PAM) with EC50 of 85 nM (hM4) and 379 nM (rM4).

VU6015241 (VU 6015241) is a highly potent and selective antagonist of M4 muscarinic acetylcholine receptor (mAChR4) with IC50 of 71 nM.VU6015241 demonstrates selectivity across multiple species, excellent aqueous solubility, and moderate brain exposure in rodents after intraperitoneal administration.

VU6019650 is a potent, highly selective M5 mAChR orthosteric antagonist with IC50 of 36 nM, >100-fold selectivity against human M1-4.VU6019650 blocked the nonselective muscarinic agonist oxotremorine-M-induced increases in neuronal firing rates of midbrain dopamine neurons in the ventral tegmental area.VU6019650 also inhibited oxycodone self-administration in male Sprague-Dawley rats without impair general motor output.

VU6028418 (VU 6028418) is a potent, highly selective, orally bioavailable M4 mAChR antagonist for the treatment of dystonia and other movement disorders.

WW-III-55 is a high-affinity, selective dopamine D3 receptor (D3R) partial agonist with Ki value of 20 nM, exhibits >800-fold binding selectivity for D3R compared with the D2R.WW-III-55 (0-5.6 mg/kg) reduced cocaine self-administration, also reduced responding for sucrose and locomotor activity.WW-III-55 attenuated yawning induced by low doses of 7-OH-DPAT (a D3R-mediated behavior).WW-III-55 (10 mg/kg) inhibited the head twitch response (HTR) by 95% in DBA/2J mice.

Zevaquenabant ((S)-MRI-1867) is a peripherally restricted, orally bioavailable dual CB1 receptor/iNOS inhibitor.Zevaquenabant ((S)-MRI-1867) (3 mg/kg, p.o.) ameliorated obesity-induced kidney morphological and functional changes via decreasing kidney inflammation, fibrosis, oxidative stress, and renal injury.The hybrid CB1R/iNOS inhibitor Zevaquenabant ((S)-MRI-1867) has greater antifibrotic efficacy than inhibition of CB1R alone.(S)-MRI-1867 reduced hepatic steatosis and the rate of hepatic VLDL secretion, upregulated hepatic LDLR expression, and reduced the circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) in diet-induced obesity (DIO mice).

ZY12201 is a potent, selective, orally bioavailable TGR5 agonist with hTGR5 EC50 of 57 pM and mTGR EC50 of 62 pM.ZY12201 displays a favorable pharmacokinetic properties and demonstrated in-vivo glucose lowering effects in animal models (ED50 of 7.9 mg/kg and ED90 of 29.2 mg/kg).

N-Arachidonyldopamine is a potent and selective endogenous CB1 receptor agonist with a Ki of 250 nM. N-Arachidonyldopamine is also a potent and selective TRPV1 agonist an with EC50 of ~ 50 nM.

GAT564 (Compound 15d) is a potent allosteric modulator of cannabinoid 1 receptor (CB1R) with EC50s of 87 and 320 nM respectively for cAMP and β-arrestin2. GAT564 markedly promotes orthosteric ligand binding to hCB1R. GAT564 is efficacious as a topical agent that significantly reduces intraocular pressure (IOP) in the ocular normotensive murine model of glaucoma.

Eptazocine (Sedapain) is a κ-opioid receptor agonist and μ-opioid receptor antagonist. Eptazocine has the effect of relieving pain.

U-75302 is a potent inhibitor of leukotriene B4. U-75302 is a pyridine analogue. U-75302 has the potential for the research of inflammatory diseases.

AP5 sodium is a potent, orall active, and selective GPR40 receptor agonist with a positive allosteric modulation of endogenous ligand (AgoPAM). AP5 sodium demonstrates rat and human inositol monophosphate (IP1) EC50 values of 0.49 nM and 0.8 nM against the GPR40 receptor, respectively. AP5 sodium has the potential for type II diabetes research.

ATL-801, an A2B receptor selective antagonist, ameliorates murine colitis.