ML2-SA1 is a potent, selective and efficacious activator (agonist) of TRPML2 with EC50 of 1.24 uM and 2.38 uM for human and mouse TRPML2, respectively.ML2-SA1 displays high selectivity for TRPML2 and no significant activity at the related TRPML1 and TRPML3 channels.ML2-SA1 directly stimulates release of the chemokine CCL2 from macrophages, also stimulates macrophage migration, thus mimicking CCL2 function.

ML204 is a potent, selective antagonist of TRPC4 and TRPC5 channels, inhibits TRPC4β-mediated intracellular Ca(2+) rise with IC50 of 0.96 uM, exhibits 19-fold selectivity against TRPC6 channel; blocks TRPC4β currents activated through either μ-opioid receptor stimulation (50 nm DAMGO, IC50=3.55 uM) or intracellular dialysis of GTPγS (IC50=2.85 uM); shows no appreciable block by 10-20 uM for TRPV1, TRPV3, TRPA1, and TRPM8, as well as KCNQ2 and Nav Channels; also inhibits TRPC5 channel currents activated through co-stimulation of Gi/o and Gq/11 signaling by μ-opioid and M3-like muscarinic receptors.

MC-100093 (MC100093) is a potent, orally bioavailable upregulator of GLT-1 and devoid of antimicrobial properties.MC-100093 enhanced uptake of glutamate into astrocytes in a mouse neuron/astrocyte co-culture model with IC50 of 0.1 uM.MC-100093 restored the expression of NA core GLT-1.MC-100093 (50 mg/kg) attenuated cue-primed relapse to cocaine-seeking without reducing motivation to consume regular chow or sucrose pellets or affecting body weight.

Kv2.1-syntaxin inhibitor 15 (Kv2.1-syntaxin-IN-15, Cpd5) is a small molecule Kv2.1-syntaxin-binding inhibitor (IC50=5.5 uM) with neuroprotective properties.Kv2.1-syntaxin inhibitor 15 competitively binds syntaxin against C1aB-containing Kv2.1 peptides with IC50 of 5.5 uM.Kv2.1-syntaxin inhibitor 15 (10 uM) significantly diminished threo-β-benzyloxyaspartate (TBOA, 75 uM)-induced toxicity neuronal cultures, ameliorated significant cellular damage, by preventing the expression of enhanced Kv2.1-mediated K+ currents.Kv2.1-syntaxin inhibitor 15 is a first-in-class inhibitor of Kv2.1 binding to Syntaxin, likely due to inhibition of the C1a region of Kv2.1 binding to syntaxin.Cpd5 (10 μM) does not affect evoked AMPAR EPSCs in layer 2/3 corticocallosal neurons in the mouse auditory cortex.

KPR-5714 (KPR5714) is a novel potent, selective TRPM8 antagonist with IC50 of 25.3 and 22.4 nM against hTRPM8 and rTRPM8, respectively.KPR-5714 dispalys 400-fold against human TRPA1, TRPV1, and TRPV4, and does not show inhibitory effects for ASIC1a, ASIC3, Nav1.3, Nav1.5, Nav1.6, Nav1.7, and Nav1.8 (IC50 values >10 uM).KPR-5714 (i.p.) inhibited the hyperactivity of mechanosensitive C-fibers of bladder afferents and dose-dependently increased the intercontraction interval shortened by intravesical instillation of acetic acid in anesthetized rats.KPR-5714 (orally administered) dose-dependently increased the mean voided volume and decreased voiding frequency without affecting total voided volume in vivo.

KNa1.1 inhibitor 31 is a potent, selective, orally available inhibitor of sodium-activated potassium channel KNa1.1 (Slack, Slo2.2) with IC50 of 40 nM (hKNa1.1 WT).KNa1.1 inhibitor 31 reduced seizures and interictal spikes in a mouse model of KCNT1 GoF.

JW-65 (JW65) is a selective, potent,CNS-permeable TRPC3 inhibitor improved stability compared to Pyr3.JW-65 shows similar potency and selectivity on TRPC3 channels, but is metabolically much more stable than its precursor, demonstrated by its much longer half-life (>4 h) in mouse, rat, and human liver microsomes when compared to Pyr3.JW-65-treated mice showed substantially decreased susceptibility to PTZ-induced seizures in a dose-dependent manner.

Hv1 inhibitor HIF is a novel inhibitor of the voltage-gated proton channel Hv1 interacts with the Hv1 VSD in the up and down states.HIF rapidly inhibits proton conduction in the up state by blocking the open channel.HIF interacts with a second site that is accessible in the down state and is responsible for key features of HIF-mediated inhibition, such as the slow component of current decay and the slow recovery from inhibition.The voltage-gated proton channel Hv1 plays important roles in numerous biological processes, including pH homeostasis, the immune response, and sperm cell function.Hv1 channel belongs to the large family of proteins containing voltage-sensing domains (VSDs), which also includes Nav, Kv, and Cav channels and voltage-sensitive phosphatases.

HEI3090 (HEI-3090) is a small-molecule P2RX7 activator (positive modulator) of purinergic P2RX7 receptor (P2X7R), enhances the P2RX7-mediated intracellular calcium concentration (Emax=250 nM).HEI3090 inhibits tumor growth and combined with αPD-1 immunotherapy ameliorates mice survival.Dendritic cells (DCs) mediate the antitumor activity induced by HEI3090.HEI3090 induces the production of mature IL-18 in the presence of eATP, triggers antitumor responses mediated by IL-18-induced NK and CD4+ T cells.HEI3090 combined with αPD-1 induces antitumor memory immune response.

HCN4 inhibitor EC18 (EC18) is a HCN4-prefering blocker.

GSK-5498A is a potent, selective small molecule blocker of Calcium-Release Activated Calcium (CRAC) channel with IC50 of 1 uM; completely inhibits calcium influx through CRAC channels, inhibits mediator release from mast cells, and pro-inflammatory cytokine release from T-cells from multiple human and rat preparations.

GSK205 derivative 16-8 is a specific small molecule dual-inhibitor of TRPV4 and TRPA1 with IC50 of 0.45 and 0.41 uM, respectively; displays no inhibitory potency toward TRPV1, TRPV2 and TRPV3; effectively attenuates formalin-evoked trigeminal irritant pain in model of acute pancreatitis.

Glutor (Glucose uptake inhibitor Glutor) is a novel highly potent glucose uptake inhibitor (IC50=10.8 nM) that selectively targets glucose transporters GLUT-1, -2, and -3.Glutor reduced the uptake of 2-DG with similar potency in different cancer cell lines such as HCT116 (IC50 =10.8 nM), UM-UC-3 (IC50=8.3 nM), UO31 (IC50=3.6 nM), and MIA PaCa-2 (IC50=1.1 nM).Glutor did not interfere with cellular hexokinase activity and potently reduced glycolytic flux in HCT116 cells.Glutor induced upregulation of GLUT-1 and -3 in cancer cells, inhibited glycolysis and efficiently suppresseed the growth of various cancer cell lines.Glutor potently and synergistically inhibited colon cancer cell growth combined with glutaminase inhibitor CB-839.

Etripamil (MSP-2017) is a novel intranasal non-dihydropyridine calcium channel blocker that has begun phase III clinical trials for the treatment of paroxysmal supraventricular tachycardias.

DRB18 (DRB-18) is a potent, pan-class I glucose transporter (GLUT) inhibitor, reduces glucose uptake in HEK293 cell lines expressd single GLUT1-4 with IC50 of 0.9-8.8 uM.DRB18 reduced cell viability in a dose-dependent manner in cancer cell lines (A549 IC50=3.5 uM, HeLa IC50=1.3 uM), also exhibited IC50 values < 10 μM in all nine melanoma cell lines.DRB18 rapidly and potently inhibited glucose transport and glucose metabolism, inhibited multiple metabolic pathways associated with glucose metabolism in A549 cells.DRB18 caused G1/S phase arrest and increased oxidative stress in A549 cells.DRB18 (10mg/kg) inhibited the growth of A549 tumors xenografted in nude mice.

DCBS152A is a potent, functionally selectiver negative modulator of GABAA receptor at the modulatory PQ site in some receptor isoforms.

DA-0218 (DA0218) is a novel potent, selective Nav1.7 inhibitor, inhibits sodium currents in Nav1.7-expressing human embryonic kidney 293 cells with IC50 of 0.74 uM.DA-0218 has no effect on sodium currents in Nav1.5-transfected human embryonic kidney 293 cells in patch-clamp experiments.DA-0218 shows analgesic activity predominantly in phase II in formalin-induced inflammatory pain mouse model.DA-0218 produced acute reduction in paclitaxel-induced mechanical allodynia, and inhibited histamine-induced acute itch and lymphoma-induced chronic itch.

CDD-1102 (CDD1102) is a potent, selective second bromodomain (BD2) of BRDT and BRD4 inhibitor with IC50 of 7 and 25 nM, >1,000-fold and 300-fold selectivity over BRDT-BD1 and BRD4-BD1.

BI-8668 (BI 8668) is a highly potent and selective epithelial sodium channel (ENaC) inhibitor, inhibits Na+ current with IC50 of 17 nM (Ussing chamber assay); BI-8668 inhibits ENaC-mediated water permeability through cell monolayers of the cell line M-1 (M-1 cells: mouse kidney tubules cells) with 81% inhibition at 3 uM.

Benzopyran-G1 is a selective inhibitor of cardiac acetylcholine-activated inwardly rectifying K+ current (IKACh), composed of Kir3.1/Kir3.4 heterotetrameric and Kir3.4 homotetrameric channel subunits.

Bamocaftor (VX-659) is a next-generation CFTR corrector, restores F508del-CFTR protein function.

ASIC1a inhibitor 5b is a highly selective and potent ASIC1a inhibitor, inhibits proton-evoked ASIC1a currents with an apparent IC50 of 27 nM at pH 6.7.ASIC1a inhibitor 5b can potently and selectively inhibit acid-induced activation of ASIC1a-containing channels, including both ASIC1a homotrimers and ASIC1a-ASIC2 heterotrimers, in a pH-dependent manner.ASIC1a inhibitor 5b binds to the acidic pocket of ASIC1a, exhibits a dramatic leftward shift under pH 6.7 activation of ASIC1a as compared to pH 6.0.ASIC1a inhibitor 5b protected neurons from ASIC1a-dependent cell death and is blood-brain barrier permeable.ASIC1a inhibitor 5b (5 mg/kg) attenuated neurological impairment and alleviated infarct volume in mouse MCAO model of ischemic stroke.

ARN24092 (ARN-4092) is a potent, selective inhibitor of Na+-K+-Cl- importer NKCC1, shows significant dose-dependent inhibition of NKCC1 in the Ca2+ influx assay (51.9% at 100 uM).ARN24092 did not show any significant inhibition of NKCC2 in the Cl-influx assay nor inhibition of KCC2 in the thallium (Tl) influx assay.ARN24092 (i.p, 0.6 mg/kg, daily) restored the short-term working memory of Ts65Dn mice in the T-maze test, completely restored associative memory in Ts65Dn mice in the contextual fear-conditioning (CFC) test, without side effects showed in health of the mice.

ARN23765 (ARN 23765) is a highly potent, pharmacological corrector of the mutant CFTR chloride channel with EC50 of 38 pM in cellular assays; ARN23765 is more than 5000-fold lower compared to presently available corrector drugs. ARN23765 also showed high efficacy, synergy with other types of correctors, and compatibility with chronic VX-770 potentiator.

AP-202 (AP202) is a highly potent and selective α4β2 nAChR antagonist with binding Ki of 18 nM, 57-fold selectivity over α3β4 receptor.AP-202 is agonist activity, also dispalys 40-fold, 10-fold and 90-fold selectivity over α4β4, α3β2, α3β4α5 receptors, does not activate α7 nAChR or block acetylcholine induced changes in membrane potential.AP-202 showed significant activity in blocking nicotine priming-induced as well as cue-induced reinstatement of nicotine seeking in vivo.

AM237 is a selective TRPC5 channel activator that potently activated homomeric TRPC5:C5 channels (EC50=15–20 nM in Ca2+i assays).AM237 did not activate TRPC4:C4, TRPC4-C1, TRPC5-C1, TRPC1:C5, and TRPC1:C4 channels, or native TRPC1:C4 channels in A498 cells, but potently inhibited EA‐dependent activation of these channels with IC50 values ranging from 0.9 to 7 nM.AM237 (300 nM) did not activate or inhibit TRPC3, TRPC6, TRPV4, or TRPM2 channels.AM237 potentiated TRPC5:C5 channels activation by sphingosine‐1‐phosphate but suppressed activation evoked by (−)‐englerin A (EA).AM237 concentration‐dependently suppressed further activation of Ca2+ influx mediated by EA with IC50 of 13 nM, potentiated TRPC5:C5 activation by S1P.Pico145 is a competitive antagonist of AM237‐mediated TRPC5:C5 activation.

SAR340835 (SAR 340835, SAR296968 prodrug) is a potent, selective Na+/Ca2+ exchanger (NCX) inhibitor, a water-soluble prodrug of SAR296968.

SAR296968 (SAR 296968) is a potent, selective Na+/Ca2+ exchanger (NCX) inhibitor, potently inhibits hNCX1/2/3 with IC50 of 74/23/129 nM, respectively.SAR296968 showed the same range of inhibitory potency on NCX1 orthologs from dog, guinea pig, pig, rabbit, and rat (IC50=20-200 nM).SAR296968 inhibited both the forward and reverse mode of the NCX current in a concentration-dependent manner with similarly high potency in voltage-clamp studies in guinea pig cardiomyocytes.SAR296968 displays little to no effect against 5-HT2B, benzodiazepine peripheral receptor, norepinephrine uptake, dopamine uptake, AR and PR.SAR296968 exhibited antiarrhythmic properties in animal models of arrhythmias related to early or late afterdepolarizations, significantly increased left ventricular contractility in anesthetized pigs.

Neurounina-1 is a small molecule Na+/Ca2+ exchanger (NCX) activator, stimulates NCX1 and NCX2 activities with EC50 of 1.1-2.7 nM, does not affect NCX3 activity.Neurounina-1 (10 nM) reduced cell death of primary cortical neurons exposed to oxygen-glucose deprivation followed by reoxygenation, also reduced γ-aminobutyric acid (GABA) release, enhanced GABA(A) currents, and inhibited both glutamate release and N-methyl-d-aspartate receptors in vitro.Neurounina-1 effectively protects against stroke damage in vivo.

A potent, specific and mixed glycine transporter subtype 1 (GlyT1) inhibitor (pIC50=7.7) and GPR55 agonist (pEC50=6.5); shows no activity across a set of more than 200 validated molecular target assays from diverse classes, including kinases, proteases and other enzymes, GPCRs.