GPCR/G-Protein

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

2,3-dinor-11β-Prostaglandin F2α (2,3-dinor-11β-PGF2α) was recovered from the urine of both normal monkeys and humans when infused with radiolabeled PGD2, where

MRS2179 blocks turkey P2Y1 receptor (Kb 102 nM, pA2 6.99), affects platelet aggregation, and has varying IC50s on P2 receptors.

Rivenprost, selective EP4 agonist (Ki: 0.7 nM), promotes bone growth, osteoblast differentiation, and aids wound healing.

L-796778 acetate is a selective sst3 receptor agonist. In CHO-K1 cells expressing hsst3 receptors, it acts as a partial agonist that inhibits Forskolin-induced cAMP production, with an IC50 value of 18 nM. Additionally, L-796778 acetate exhibits anticonvulsant properties.

Compound 29 is a potent, CB2-selective antagonist/reverse agonist. Derivatives 23 & 24 offer antinociception; 24 activates cannabinoid/TRPV1 receptors.

NK1 Receptor Antagonist 2, a compound targeting the NK1 receptor, holds potential for tinnitus and hearing loss research.

YM158 free base is a potent and selective antagonist of TXA2 and LTD4 receptor (pA2s: about 8.81 and 8.87).

<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>

Nolpitantium besilate is a neurokinin-1 receptor antagonist.

Udifitimod (BMS-986166) is a potent, selective, and orally active modulator of the S1P1R receptor, showing potential for research in autoimmune diseases.

<p>GRKs-IN-1 has remarkable potency against and selectivity for G protein-coupled receptor kinase 2 GRK2 (IC50: 130 nM) and GRK5 (IC50: 7.1 μM).</p>

NPR-C activator 1 is an activator of the natriuretic peptide receptor C (NPR-C), which can be used to study cardiovascular diseases.

MCTR1, a pro-resolving mediator derived from DHA, promotes tissue repair and reduces inflammation by enhancing phagocytosis and decreasing eicosanoids.

CI-936 (MRS-3310) is an orally active A2 agonist with a binding affinity of 25 nM. In preclinical studies, it has demonstrated potent and selective effects, indicating potential antipsychotic efficacy. Additionally, CI-936 inhibits exploratory behavior in mice.

RWJ-68022 (Example 9) is a cyclopentene derivative that serves as a motilin receptor antagonist. It competes with motilin and erythromycin at motilin receptor sites and is applicable in research on gastrointestinal disorders.

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

CCR3 antagonist2 (example 66) is a CCR3 antagonist useful for researching inflammatory or allergic diseases, particularly those affecting the respiratory tract, such as inflammatory or obstructive airway conditions.

Tixanox sodium effectively blocks histamine release in the lungs triggered by anti-IgE. It has also been demonstrated that when administered orally, Tixanox sodium can successfully counteract exercise-induced asthma.

MRS4833 (compound 15) is an orally active, potent, competitive antagonist of P2Y14R, exhibiting IC50 values of 5.92 nM for hP2Y14R and 4.8 nM for mP2Y14R. It reduces airway eosinophilia in protease-mediated asthma models and reverses chronic neuropathic pain in mouse CCI models.

P2Y2 and P2Y4 receptor agonist

Fosrolapitant is an antagonist of the neurokinin 1 (NK1) receptor.

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

BMS-986104 is an effective selective modulator of the S1P1 receptor. It demonstrates efficacy in the mouse EAE model, comparable to that of FTY720. Furthermore, BMS-986104 shows promising remyelination properties in three-dimensional brain cell cultures subjected to lysophosphatidylcholine (LPC)-induced demyelination.

Remlifanserin is a potent inverse agonist of the serotonin receptor (5-HT2A).

Aplaviroc (AK 602), a SDP derivative, is a CCR5 antagonist. With IC50s of 0.1-0.4 nM for HIV-1Ba-L, HIV-1JRFL and HIV-1MOKW.

<p>AChE/BChE-IN-21 is an antagonist of the histamine H3 receptor, a calcium channel blocker, and an acetylcholinesterase inhibitor. It exhibits neuroprotective activities against H2O2 and Aβ1-40, and can restore cognitive functions in AD mice.</p>

Substituted piperidines-1 can promote the release of growth hormone in humans and animals.

<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>

MK-8318 is an effective and selective antagonist of the CRTh2 receptor (Ki: 5.0 nM).

<p>AB-FUBINACA 3-fluorobenzyl isomer is a synthetic cannabinoid and an indazole derivative, exhibiting high affinity for central CB1 receptors (Ki= 0.9 nM) and possessing anticonvulsant activity.</p>

PD 135158 is a CCK2 receptor antagonist.

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.

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

Terguride: treats hyperprolactinemia, blocks 5-HT2A/B, activates dopamine receptors, studied for PAH.

<p>O-1269 acts as a partial agonist for the cannabinoid receptor 1 (CB1R), with a binding affinity (Ki) of 32 nM. Additionally, it exhibits analgesic properties.</p>

BAY-3153 is a selective CCR1 ( C-C motif chemokine receptor 1 ) antagonist (human IC 50 =3 nM ; rat IC 50 =11 nM ; mice IC 50 =81 nM) .

<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>

SSTR5 antagonist 2 hydrochloride: potent, oral SSTR5 blocker with potential in type 2 diabetes research.

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>

BIBO3304 (diTFA), a selective neuropeptide Y (NPY) Y1 receptor antagonist, demonstrates oral efficacy. It exhibits high affinity for Y1 receptors in both humans and rats, with IC50 values of 0.38 nM and 0.72 nM, respectively. Additionally, BIBO3304 (diTFA) enhances bone-tendon healing via the Wnt/β-catenin signaling pathway [1] [2] [3].

COX-2-IN-6: Potent, selective COX-2 inhibitor; oral; IC50 0.84μM, Ki 69nM; blocks PGE2 synthesis; prevents colorectal cancer.

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>Ersentilide, a benzamide derivative, functions as both a β1-adrenergic receptor antagonist and an Ikr blocker. It has demonstrated efficacy in animal models of cardiac arrhythmias.</p>

N-methyl LTC4 is a stable synthetic analog of LTC4 and a selective CysLT2 agonist, useful in studying leukotriene pharmacology.

GPR183 inverse agonist-1 (Compound 78) is an inverse agonist of GPR183. It inhibits GPR183-mediated Gi activation and β-arrestin2 recruitment while blocking PBMC migration. This compound is utilized in research concerning inflammation, autoimmune, and cancer-related diseases.

MRS4865 (compound 7a) serves as a chimeric antagonist for the P2Y14 receptor and an agonist for UDP-glucose, offering protection against neuropathic pain.

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.

<p>CBR Agonist-2: CB1 receptor agonist, EC50 - 960 nM, Ki - 970 nM, useful for hCB1R-related disease research.</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>

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

Y1 receptor antagonist 1 is an antagonist of neuropeptide Y1 receptor.

<p>Opipramol (Ensidon) is an atypical tricyclic antidepressant (TCA) primarily functioning as a sigma (σ) receptor agonist. It interacts effectively with sigma recognition sites, having a Ki value of 50 nM. Opipramol is applicable in the study of generalized anxiety disorder (GAD).</p>

<p>CRHR1 antagonist 1 (compound 10a) is a non-peptide antagonist of corticotropin-releasing hormone receptor 1 (CRHR1). It serves as a useful tool in the study of psychiatric disorders.</p>

Iralukast is a cysteinyl-leukotriene antagonist (CysLT) with a pKi of 7.8 for CysLT1.

<p>Rocavorexant is an antagonist of the orexin-1 receptor (orexin-1 receptor), exhibiting a pIC50 value of 9.1 for human OX1 and a pIC50 of 6.0 for human OX2.</p>

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

<p>A2A receptor antagonist 2 is a highly selective and potent antagonist of the adenosine A2Areceptor (IC50: 8.3 nM).</p>

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

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.

LAS195319 is a potent and selective inhaled PI3Kδ Inhibitor (IC50 = 0.5 nM) for the Treatment of Respiratory Diseases.

RXFP1 receptor agonist-10 (Compound 188) is an RXFP1 receptor agonist with an EC50 of 0.5 nM. It is useful for research into heart failure.

<p>Cicaprost (ZK 96480) is an IP agonist with artery relaxing effects; EC50 is 5.8 nM.</p>

Tonapofylline, orally active, selectively blocks A1 adenosine receptor (Ki: 7.4 nM), used in heart failure research.

RXFP1 receptor agonist-9 is a potent RXFP1 agonist with an EC50 value of 2.5 μM and a Ymax of 65%. This compound exhibits significant microsomal stability, desirable pharmacokinetic properties, and pharmacodynamic activity. RXFP1 receptor agonist-9 is useful in the study of heart failure.

NPRA agonist-11 (Example 161) is an NPRA (NPR1) agonist with AC50 values of 1.681 μM and 0.989 μM for human and monkey, respectively. It is applicable in research on cardiovascular and other diseases.

<p>Metrazoline (o-Methyl-tracizoline) acts as a ligand for adrenergic receptors (low affinity) and imidazoline I2 receptors.</p>

inhibitor of human CCR5 binding to HIV-1 gp120

LAB687 (Compound 2a) is an inhibitor of microsomal triglyceride transfer protein (MTP) with an IC50 of 0.9 nM for inhibiting the secretion of apolipoprotein B (apoB) in HepG2 cells. Additionally, LAB687 acts as a Smoothened (Smo) antagonist, exhibiting IC50 values of 2.48 μM and 3.42 μM for mouse and human Smo receptors, respectively. This compound is effective in reducing triglyceride and low-density lipoprotein cholesterol (LDL-C) levels and in inhibiting the Hedgehog signaling pathway.

Osanetant HCl is the (R)-enantiomer; neurokinin-3 receptor antagonist

GLP-1R agonist 33 (Compound 224) is a GLP-1 receptor agonist with potential applications in research related to diabetes, obesity, and non-alcoholic fatty liver disease (NAFLD).

MSX-3 is an antagonist of the A2A adenosine receptor and a prodrug of MSX-2.

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

Selective, high affinity competitive antagonist of the P2Y1 receptor

<p>MF-592: EP4 receptor antagonist, hEP4 IC50 3 nM, hWB IC50 78 nM, great oral PK, rat arthritis ED50 0.1 mg/kg/day, promising for development.</p>

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

<p>(±)-Penbutolol ((Rac)-Penbutolol) is the racemic form of Penbutolol. It acts as an orally active β-adrenergic receptor antagonist. (±)-Penbutolol mitigates the tachycardia induced by exercise, reduces the increase in peak expiratory flow rate (PEFR) caused by physical activity, and decreases plasma renin activity (PRA) at rest. The peak plasma concentration of this compound is achieved one hour after oral administration, with a half-life of 4.5 hours, and it is metabolized into active metabolites in the body. This compound is utilized in research related to cardiovascular diseases.</p>

U91356 is an agonist of the dopamine receptors.

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

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

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

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

<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>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>

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

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

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

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

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

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.

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

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

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

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

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

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.

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

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).

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

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

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.