An E3 ligase ligand-linker conjugate for PROTAC.

Bis(tributylammonium) difluoromethylenediphosphonate

Afobazole is a multi-targeted anxiolytic drug with neuroprotective activities. It binds to the sigma-1, melatonin MT1, and MT3 receptors, as well as monoamine oxidase A (MAO-A, Kis = 5.9, 160, 0.97, and 3.6 µM, respectively, in a radioligand binding assay). Afobazole (5 mg/kg) decreases the latency to enter, as well as increases the number of entries into and percentage of time spent in, the open arms of the elevated plus maze, indicating anxiolytic-like activity in passive stress-coping BALB/c, but not active stress-coping C57BL/6, mice. It decreases stroke volume and neuronal and oligodendroglial cell death in the brain in a rat model of ischemia induced by middle cerebral artery occlusion (MCAO) when administered at doses of 0.3 and 3 mg/kg.

OSMI-1 is a cell-permeable, small molecule O-GlcNAc transferase (OGT) inhibitor with IC50 of 2.7 uM.

AUNP-12 (Aurigene-012) is a PD-1 inhibitor peptide, blocks the PD-1/PD-L1, PD-1/PD-L2 and PD-L1/CD80 pathways.

BRD0705 is a potent, paralog-selective GSK3α inhibitor with IC50 of 66 nM, 8-fold selectivity over GSK3β (IC50=515 nM).

RGX-104, also known as SB 742881, is a liver X receptor beta agonist with potential immunomodulating and antineoplastic activities. Upon oral administration, RGX-104 selectively targets and binds to LXRbeta, thereby activating LXRbeta-mediated signaling, leading to the transcription of certain tumor suppressor genes and the downregulation of certain tumor promoter genes. This particularly activates the expression of apolipoprotein E (ApoE), a tumor suppressor protein, in tumor cells and certain immune cells. This activates the innate immune system, resulting in depletion of immunosuppressive myeloid-derived suppressor cells (MDSCs), tumor cells and endothelial cells in the tumor microenvironment. This reverses immune evasion, enhances anti-tumor immune responses and inhibits proliferation of tumor cells.

(R)-IMPP is a cell-permeable inhibitor of the secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9; IC50 = 4.8 µM).

Lasmiditan, also known as COL-144 and LY573144, is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist (K1=2.21 μM) without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study. Lasmiditan showed efficacy in its primary endpoint, with a 2-hour placebo-subtracted headache response of 28.8%, though with frequent reports of dizziness, paresthesias, and vertigo.

Pexidartinib hydrochloride (PLX-3397 hydrochloride) is a potent, orally active, selective, and ATP-competitive colony stimulating factor 1 receptor (CSF1R or M-CSFR) and c-Kit inhibitor, with IC50s of 20 and 10 nM, respectively. Pexidartinib hydrochloride exhibits 10- to 100-fold selectivity for c-Kit and CSF1R over other related kinases. Pexidartinib hydrochloride induces cell apoptosis and has anti-cancer activity.

Nemifitide diTFA (INN 00835 diTFA) is a synthetic pentapeptide antidepressant with a potential for rapid onset of action. Nemifitide diTFA is a peptide analog of melanocyte-inhibiting factor (MIF). Nemifitide diTFA can cross the blood-brain barrier.

ASN-002 (Gusacitinib, ASN002) is a novel and potent dual inhibitor of SYK/JAK kinases with IC50 of 5-46 nM in biochemical assays.

ML359 is a small molecule, specific inhibitor of Protein disulfide isomerase (PDI) with IC50 of 250 nM; displays >100-fold selectivity over other thiol isomerases (Erp5, Thioredoxin, Thioredoxin reductase); shows no cytotoxicity in three human cell lines, and some activity in inhibiting platelet aggregation in vitro.

VU0134992 (VU 0134992) is a potent, selective blocker of the inward rectifier potassium channel Kir4.1 (KCNJ10) with IC50 of 0.97 uM in whole-cell patch clamp electrophysiology assays; displays 9-fold selectivity for homomeric Kir4.1 over Kir4.1/5.1 concatemeric channels (IC50=9 uM) at -120 mV; VU0134992 is greater than 30-fold selective for Kir4.1 over Kir1.1, Kir2.1, and Kir2.2, is weakly active toward Kir2.3, Kir6.2/SUR1, and Kir7.1, and is equally active toward Kir3.1/3.2, Kir3.1/3.4, and Kir4.2 in Tl+ flux assays; causes dose-dependent diuresis, natriuresis, and kaliuresis in rats after oral treatment; VU0134992 represents the first in vivo-active tool compound for probing the therapeutic potential of Kir4.1 as a novel diuretic target for the treatment of hypertension.

GR-73632 is a potent and selective tachykinin NK1 receptor agonist with EC50 of 2 nM, promotes differentiation but not survival of rat chromaffin cells in vitro..

SCH-23390 is a potent dopamine receptor antagonist (Ki values are 0.2 nM and 0.3 nM at D1 and D5 receptor sub-types, respectively). SCH-23390 is also an agonist at 5-HT1C and 5-HT2C receptors in vitro (Ki values are 6.3 nM and 9.3 nM respectively). It blocks quinpirole-induced Kir3 (GIRK) currents (EC50 = 268 nM) independently of receptors.

Nidufexor (LMB763, LMB-763) is a novel potent farnesoid X receptor (FXR) agonist for the treatment of non-alcoholic steatohepatitis (NASH) and hepatobiliary disorders.

Mizagliflozin (DSP-3235, KGA-3235, GSK-1614235) is a potent, selective, orally active SGLT1 inhibitor with Ki of 27 nM, displays >350-fold selectivity over SGLT2.

Z433927330 (Z 433927330) is a potent and selective aquaporin-7 (AQP7) inhibitor, inhibits glycerol permeability in erythrocytes with IC50 of 0.6 uM..

TAK-931 (Simurosertib) is a potent, selective, ATP competitive and orally bioavailable inhibitor of Cdc7 with IC50 of <0.3 nM.

K-604 is a potent, selective and competitive ACAT-1 inhibitor with IC50 of 0.45 uM for human ACAT-1, displays 229-fold selectivity over ACAT-2.

PrNMI is a peripherally restricted cannabinoid 1 receptor (CB1R) agonist, significantly alleviates spontaneous pain behaviors in the animals.

DS-7423 is a novel potent, small-molecule dual inhibitor of PI3K/mTOR with IC50 of 15.6, 1143, 249, 262 and 34.9 nM for PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ, and mTOR  respectively.

APX001 (APX 001A;E1210) is a novel broad-spectrum antifungal agent that inhibits the fungal protein Gwt1, demonstrates significantly acitive MIC50 and MIC90 values of 0.004 and 0.031 ug/ml (16 strains of C. auris).

Sulfo-Cyanine 5 NHS Ester is a water soluble amine reactive red emitting fluorescent dye.Used for the labeling of various amine containing molecules in aqueous phase without use of any organic co-solvent. Useful for the labeling of proteins which denature in the presence of organic co-solvents, as well as for proteins with low solubility.

MTI31 (LXI-15029, mTOR inhibitor-31) is a novel potent, selective mTORC1/mTORC2 inhibitor with Kd of 0.2 nM (mTOR), displays >5,000-fold selectivity over PIK3CA, PIK3CB and PIK3G.

ZINC02092166 is a novel potent, and selective small-molecule inhibitor for the β-catenin/Tcf4 protein-protein interaction with Ki of 1.7 and 7.0 uM in AlphaScreen and FP assay (wild-type β-catenin), respectively; remain affinity for muant catenin V511S, V511S/I569S and R469A with Ki of 20-50 uM; exhibits dual selectivity for β-catenin/Tcf over β-catenin/cadherin and β-catenin/APC PPIs.

ML-T531 is a potent, selective hERG potassium channel (Kv11.1) activator with EC50 of 3.13 uM.

RP-5063 (Brilaroxazine) is a multimodal dopamine and serotonin modulator with partial agonist activity at DA D2, D3, D4, 5-HT1A, and 5-HT2ARs, and antagonist activity at 5-HT2B, 5-HT6 and 5-HT7Rs.

SMS1-IN-1, compound SAPA 1j, is a novel and the most potent sphingomyelin synthase 1 (SMS1) inhibitor with an IC50 value of 2.1 μM. SMS1-IN-1 has the potential for the treatment of atherosclerosis.