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

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.

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.

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.

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.

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.

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.

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.

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.

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-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.

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.

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.

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.

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

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

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

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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

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

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.