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.

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

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.

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

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.

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.

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.

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.

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.

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.

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

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.

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.