GPCR/G-Protein

Nifeviroc (TD-0232) is an orally active CCR5 antagonist, useful in HIV-1 infection research.

KARI 201 hydrochloride is a selective, brain-penetrant, competitive inhibitor of acid sphingomyelinase (ASM) with an IC50 of 338.3 nM. It also acts as an agonist for the growth hormone-releasing peptide receptor (ghrelin receptor). Additionally, KARI 201 hydrochloride can enhance the neuropathological features of Alzheimer's disease.

8 Hydroxy PIPAT oxalate is a selective 5-HT1A receptor agonist that enhances the spontaneous release of histamine by promoting the degranulation of mast cells in guinea pig and human intestinal preparations. By activating the serotonin signaling pathway, this compound demonstrates potential in regulating gastrointestinal functions and offers insight into the management and suppression of functional gastrointestinal disorders such as irritable bowel syndrome. Its effects in increasing histamine release could play a crucial role in gastrointestinal regulation.

BI-685509: potent, oral sGC activator, boosts cGMP, enhances NO pathways, for CKD/DKD research.

LTB4 dimethyl amide: inhibits human neutrophil degranulation and rat lysozyme release; antagonizes LTB4 receptor on guinea pig lung membranes (Ki = 130 nM).

<p>Potent, selective D4R antagonist; IC50 = 6.87 µM; potential in Parkinson’s disease research.</p>

GLP-1 receptoragonist 16 (Example 53) is a GLP-1 agonist applicable for research in diabetes, obesity, or diseases related to non-alcoholic steatohepatitis.

DSP-1053: Benzylpiperidine-based, potent SERT inhibitor (Ki=1.02nM), partial 5-HT1A receptor agonist (Ki=5.05nM), antidepressant.

LX2761 is a stable inhibitor for SGLT1/2 with IC50s of 2.2/2.7 nM; it targets SGLT1 in the GI tract.

Selective, orally active PAR-1 antagonist with an IC50 of 7 nM, potential for cardiovascular disease studies.

LY 245769 is an inhibitor of leukotriene E4 (LTE4).

AL-8810 is an 11β-fluoro analog of PGF 2α with selective antagonist effects at the PGF 2α receptor (FP receptor) [1].

ZK118182 isopropyl ester is a PG analog with potent DP-agonist activity (EC50 = 16.5 nM) and high affinity for the DP receptor (Ki = 74 nM).

Potent D4R antagonist-2: selective, IC50=6.52 μM, good in vitro PK and brain penetration, potential for Parkinson's research.

<p>Setomagpran is an antagonist of the mas-related G protein-coupled receptor (MRGPR) and possesses anti-inflammatory properties.</p>

Vibegron (MK-4618) is an effective and selective Beta 3 adrenergic receptor agonist, used to treat overactive bladder (OAB).

GLP-1 receptor agonist 15 (Example 4) is a GLP receptor agonist with an EC50 of 0.74 nM. It exhibits an IC50 of 10.1 μM against the hERG potassium ion channel. This compound is applicable for research in the diabetes field.

<p>SphK1-IN-1: SphK1 ATPase inhibitor, IC50=2.48 μM, potential for cancer research.</p>

<p>BMS-741672 is a potent, selective CCR2 antagonist for the treatment of neuropathic pain.</p>

CP-199330: non-toxic alternative to Zafirlukast & Pranlukast, blocks cysteyl LT1 receptors.

CP-608039 is a selective adenosine A3 receptor agonist for both human A3 and human A1 receptors.

AM8936: potent CB1 agonist, EC50 rCB1=8.6nM/hCB1=1.4nM, Ki rat CB1=0.55nM; potential for CNS, metabolic, pain, glaucoma research.

<p>Compound 12a (D1R antagonist 1) is a D1R antagonist that participates in both G-protein-coupled and β-arrestin-mediated signaling pathways [1].</p>

Aeruginosin 98-B, a protease inhibitor, effectively inhibits trypsin, plasmin, and thrombin with IC50 values of 0.6, 7.0, and 10.0 μg/mL, respectively.

L 156903 is a bioactive chemical. It also inhibits the binding of neurotensin to brain tissue.

SS-RJW100 is an enantiomer of RJW100 targeting LRH-1, SF-1, enhances Tif2 interaction, and disrupts LRH-1 networks with lowered stability.

Diosuxentan is an inhibitor of ETA and is utilized in research pertaining to cardiovascular, renal, and neuronal inflammatory diseases.

<p>APJ receptor agonist 8 is a small molecule agonist of the APJ receptor, enhancing load-independent cardiac contractility in isolated perfused rat hearts.</p>

<p>DA-302168S is an orally active, selective GLP-1R agonist with an EC50 value of 1.32 nM. It promotes insulin secretion and has a hypoglycemic effect. Additionally, DA-302168S reduces food intake. It primarily activates GLP-1R in humans and monkeys, with minimal effect on GLP-1R in rats, mice, and dogs. DA-302168S can be used for research in type 2 diabetes and obesity.</p>

LJ-4517 is an effective A2AAR antagonist (Ki=18.3 nM). LJ-4517 can effectively replace the binding of [3H] ZM241385 at WT A2AAR.

GPBAR1-IN-3 (Compound 14) is both a selective agonist for GPBAR1, with an EC50 value of 0.17 μM, and an antagonist for CysLT1R [1].

SSTR4 agonist 4, potent in pain research, shows promise in rodent pain models, with potential for Alzheimer's due to hippocampus activity.

<p>RGH-122 (compound 43), characterized as an orally active, potent, and selective hV1a receptor antagonist, demonstrates significant affinity with a K i value of 0.3 nM and an IC 50 of 0.9 nM. It exhibits microsomal stability, indicated by a CL int value of 13/28/25 μL/min/mg [1].</p>

Thielavin B, from Thielavia terricola, inhibits prostaglandin E2 synthesis and reduces rat oedema.

<p>Inupadenant (EOS-850) is a selective A2a receptor antagonist, targeting immunosuppression in tumors.</p>

SB 258741 hydrochloride is a potent antagonist of the 5-HT 7 receptor, designed specifically for studying schizophrenia [1].

<p>EP-3945 is an agonist of Mas-related G protein-coupled receptors (MRGPR), exhibiting greater potency than the small molecule agonist β-Alanine targeting MRGPRD. MRGPRs play a crucial role in inflammatory itch and pain perception. These receptors interact with Gq (MRGPRX2, MRGPRX4, and MRGPRX1 are coupled with Gq; MRGPRX2 and MRGPRD couple with Gi), with EP-3945 having an EC50 value of 211.6 nM for Gq.</p>

(2R,3S)-N-(4-(2,6-dimethoxyphenyl)-5-(5-methylpyridin-3-yl)-4H-1,2,4-triazol-3-yl)-3-(5-methylpyrimidin-2-yl)butane-2-sulfonamide is an Apelin receptor agonist

SGLT1/2-IN-1 is a dual SGLT1/SGLT2 inhibitor.

Pexacerfont (BMS-562086) is a selective antagonist of the corticotropin-releasing factor receptor (IC50: 6.1±0.6 nM for the human CRF1 receptor).

BAY-899, oral LH-R antagonist, IC50: 185 nM (hLH), 46 nM (rLH), lowers sex hormones in vivo.

<p>Monlunabant ((S)-MRI-1891), a solid dispersion compound, functions as an inhibitor of the cannabinoid CB1 receptor [1].</p>

<p>M1069 is an oral A2A/A2B receptor antagonist, 100x more selective over A1/A3, with antitumor properties by blocking adenosine's immunosuppressive effects.</p>

Selective, high affinity competitive antagonist of the P2Y1 receptor

<p>SGL5213 is a potent oral SGLT1 inhibitor (IC50: 29 nM) with potential for treating type 2 diabetes.</p>

<p>CB1 antagonist 4 is an inverse agonist of cannabinoid receptor 1 (CB1) with an IC50 of 0.4 nM. It can reduce body weight, improve plasma inflammatory markers, and enhance glucose homeostasis [1].</p>

<p>HU-308, a synthetic cannabinoid analogue, is a highly selective agonist of the CB2 receptor. It demonstrates an affinity for the CB2 receptor that is over 440 times greater than its affinity for the CB1 receptor, which are predominantly found in immune cells. This compound plays a crucial role in modulating the immunosuppressive effects of the endocannabinoid system (ECS). Additionally, HU-308 possesses anti-inflammatory and neuroprotective properties, and it regulates the function of microglia. Its potential applications include research into neuroinflammation and retinal diseases.</p>

Merigolix is a potent gonadotrophin releasing hormone (GnRH) antagonist .

GRPR antagonist-1 targets GRPR, kills specific cancer cells (e.g., PC3, Pan02, HGC-27), and promotes apoptosis by modulating Bcl-2 and Bax.

Pareptide monohydrochloride is a metabolically stable analog of melatonin inhibitor (MIF).

RU 52583 is an alpha 2-adrenergic receptor antagonist.

MrgprX2 antagonist-6 is a potent antiallergic agent with inhibitory effects on mast cell degranulation.

<p>(S)-YNT-3708 is the S-isomer of YNT-3708, demonstrating relatively low activity against OX1R and OX2R receptors, with EC50 values of 3595 nM and 1661 nM, respectively.</p>

Apafant (WEB 2086) is a PAF antagonist that blocks eosinophil activation and can be used to study experimental allergic conjunctivitis in guinea pigs.

RS 61756-007 is a selective thromboxane receptor (TP) agonist.

Beloxepin is an oral dual selective inhibitor of serotonin and norepinephrine uptake.

LK-11, an alkaloid derivative, inhibits the passive uptake of norepinephrine (NA) by synaptic vesicles in the thalamus, similarly to cocaine.

Pentacosafluorotridecanoic Acid (PFTrDA) is a perfluoroalkyl substance (PFAS) that exhibits various biological impacts across different species. In zebrafish embryos, exposure to PFTrDA induces yolk sac edema and increases mRNA expression of thyroid hormone synthesis genes, including tshβ, at concentrations of 0.1 and 0.3 mg/L. At a dosage of 10 mg/kg, PFTrDA reduces serum testosterone and luteinizing hormone levels, as well as palmitic acid, linoleic acid, and oleic acid levels in the testicular interstitial cells of late adolescent rats. In humans, maternal plasma levels of PFTrDA during pregnancy are positively correlated with the development of eczema in female infants (but not male infants), and PFTrDA levels are higher in the livers of cancerous humans compared to non-cancerous ones. Additionally, PFTrDA is found in marine mammals.

KF26777 is a potent and selective antagonist of adenosine A3 receptor.

BAY 38-7271: potent neuroprotective, selective CB1/CB2 agonist, Ki of 1.85 nM (CB1) & 5.96 nM (CB2).

<p>AFP-07 is a highly selective and potent agonist. It was used for the prostacyclin receptor.</p>

<p>Arpromidine (BU-E-50) acts as an agonist for the histamine H2 receptor and an antagonist for the histamine H1 receptor. It demonstrates positive inotropic effects with a lower risk of inducing arrhythmias. Arpromidine can be utilized in studies related to congestive heart failure.</p>

MK-0812 is a dual antagonist of the CCR2 and CCR5 receptors that can alleviate adipose inflammation in ob/ob mice.

<p>SR 142948-C3-NHMe is the methylated form of SR 142948.</p>

LK-732 is a thrombin inhibitor with antithrombotic activity. It exhibits dose-dependent inhibition in models of hypercoagulability, with an IC50 value of 1.3 mg/kg. LK-732 is used in cardiovascular and cerebrovascular research.

CGRP antagonist 7 is a potent calcitonin gene-related peptide receptor (CGRP) antagonist with a Ki value of 0.029 nM. It effectively inhibits CGRP receptor-mediated cyclic adenosine monophosphate (cAMP) production, with an IC50 value of 1.5 nM. This compound is useful in migraine research.

Sulfinalol hydrochloride is an orally active β-adrenoceptor (β-adrenoceptor) antagonist that exhibits direct vasodilatory activity. It is also classified as an antihypertensive agent.

Tipindole is a serotonin antagonist utilized in research related to depression.

Butopamine hydrochloride is an orally active inotropic compound that is more effective at increasing heart rate compared to Dobutamine.

<p>Serotonin hydrogen maleate serves as a monoaminergic neurotransmitter and an endogenous 5-HT receptor agonist within the central nervous system (CNS). It also functions as an inhibitor of catechol O-methyltransferase (COMT), exhibiting a Ki value of 44 μM.</p>

<p>ATL444 is an adenosine receptor antagonist with affinity (Ki values) for rA1AR, rA2AAR, rA2BAR, and rA3AR of 7.0, 2.5, 61.8, and &gt;1000 nM, respectively.</p>

<p>MDA77 is a CB2 agonist with an EC50 value of 5.82 nM and exhibits no activity towards CB1.</p>

<p>1'-Naphthoyl-2-methylindole (Compound 88) acts as a cannabinoid mimic and an inhibitor of Win 55212-2, displaying a 34% inhibition of [3H]Win 55212-2 binding to cannabinoid receptors at a concentration of 3 μM.</p>

YM-49598 iodide is a tachykinin NK-1 receptor antagonist. It inhibits drug-induced bladder contractions in rats with an IC50 of 11 μg/kg.

SAR-150640, a selective β3-adrenergic receptor agonist, prevents an increase in MMP activity and production observed after LPS stimulation or in cases of chorioamnionitis.

Compound 6.4, also known as 5-HT7R antagonist 3, is a selective antagonist of the 5-HT7R with a Ki of 8 nM. It exhibits significantly less affinity towards D2R, 5-HT1AR, and 5-HT2AR with Ki values of 511 nM, 8930 nM, and 5786 nM, respectively. In mice, 5-HT7R antagonist 3 demonstrates anti-depressant and anti-anxiety activities.

AM11638 is an endogenous cannabinoid analogue that targets cannabinoid receptors (CB1 and CB2 receptors), exhibiting analgesic properties. It shows potential for research in neurological disorders and inflammation-related diseases.

VU0514009 is a competitive antagonist of chemokine-like receptor 1 (CMKLR1) with an EC50 of 2 nM. It effectively inhibits chemerin-9-induced arrestin recruitment and receptor internalization, significantly reducing Ca2+ flux responses in HEK293 cells. This compound shows potential for research in inflammatory diseases and metabolic syndrome.

<p>F 14679 is a potent 5-HT1A agonist (pKi=10.23) with a maximum Ca2t response similar to 5-HT.</p>

<p>Treprostinil diethanolamine (UT-15C) is a potent agonist of EP2, DP1 and IP, with values of 3.6, 4.4, 32.1, 212, 826, 2505 and 4680 nM for EP2, DP1, IP, EP1,</p>

<p>BQ-788 is an ETB receptor antagonist with potential hypertensive activity that inhibits exogenous ET-1-induced elevation of coronary perfusion pressure.</p>

<p>AZD5462 is a potent orally available relaxin receptor RXFP1 agonist for the study of heart failure and cancer.</p>

SB-423562 is a calcium-sensing receptor (CaSR) antagonist and can be used in studies about osteoporosis.

<p>AZD-5672 is an antagonist of CCR5 with an IC50 of 0.32 nM.</p>

<p>LSN3318839 is a potent and orally available glucagon-like peptide-1 receptor (GLP-1R) modulator.LSN3318839 enhances GLP-1R G-protein-coupled signaling and can</p>

<p>PF-07258669 is a selective melanocortin 4 receptor (MC4) antagonist used in the study of cachexia and loss of appetite.</p>

<p>SB-224289 hydrochloride (SB-224289A) is a selective antagonist of 5-HT1B receptor, with anxiolytic effect.</p>

<p>Dersimelagon (MT-7117) is an orally active, selective melanocortin 1 receptor (MC1R) agonist.Cost-effective and quality-assured.</p>

Vofopitant dihydrochloride (GR 205171A) is a tachykinin NK1 receptor antagonist and a potential compound for the treatment of pathologic vomiting.

Vofopitant (GR 205171) is a potent NK1 receptor antagonist with anxiolytic and antiemetic activity for the study of post-traumatic stress disorder (PTSD).

<p>BMS-986141(UDM-003183) is a selective and potent protease-activated receptor-4 (PAR-4) antagonist with oral activity and an IC50 value of 0.4 nM.BMS-98614</p>

Rolapitant HCl is a potent NK1 antagonist, non-CYP3A4 interactive, with anti-emetic effects and a Ki of 0.66 nM.

Arotinolol is a nonselective α/β-adrenergic receptor blocker and a vasodilating β-blocker. Arotinolol also shows potency for inhibiting the binding of the radioligand [125I-ICYP] to [5HT1B-serotonergic] receptor sites. It is an antihypertensive agent.

Protease-Activated Receptor-4 (PAR4) is a proteinase-activated receptor-4 agonist used in antiplatelet therapy.

Pumosetrag Hydrochloride is an orally available 5-HT3 partial agonist. It is developed for the treatment of irritable bowel syndrome and gastroesophageal reflux disease.

ML-00253764 hydrochloride is an antagonist of nonpeptidic melanocortin receptor 4 (MC4R) (Ki and IC50 of 0.16 µM and 0.103 µM, respectively).

JMV 2959 is an antagonist of growth hormone secretagogue receptor type 1a (GHS-R1a) (IC50: 32 nM).

7-Desmethyl-agomelatine, a metabolite of Agomelatine, exhibits lower activity than Agomelatine, which functions as a melatonergic (MT1 and MT2) agonist and 5-HT2C antagonist.

HOKU-81is a new bronchodilator and is one of the metabolites of tulobuterol.

BIBP3226 TFA is an effective and selective antagonist of neuropeptide Y Y1 (NPY Y1) and neuropeptide FF (NPFF) receptor (Kis: 1.1, 79, and 108 nM for rNPY Y1, hNPFF2, and rNPFF).

CYM 9484 is a selective and potent neuropeptide Y (NPY) Y2 receptor antagonist with an IC50 value of 19 nM.

ML-290 is an effective relaxin/insulin-like family peptide receptor (RXFP1) agonist and activator of anti-fibrotic genes. It shows an EC50 of 94 nM.

SR 146131 is a potent and selective agonist of the nonpeptide receptor.

Beraprost sodium is a stable and orally active prodrug of PGI2.

SHA 68 is a potent and selective non-peptide antagonist of neuropeptide S receptor (NPSR) with IC50 values of 22.0 nM for NPSR Asn107 and 23.8 nM for NPSR Ile107.

SB-399885 hydrochloride is an antagonist of 5-HT6 receptor.