GPCR/Proteína-G

<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>

<p>Nedemelteon is an agonist of the melatonin receptor (melatonin receptor).</p>

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

<p>Bzo-poxizid is a synthetic cannabinoid and a psychoactive substance.</p>

<p>MRS2905 (α,β-Methylene-2-thio-UDP) trisodium is a selective P2Y14R agonist with an EC50 of 0.92 nM. It shows no activity on UDP-activated P2Y6 receptors or other P2Y receptors.</p>

<p>Teoprolol is a blocker of β-adrenergic receptor.</p>

<p>CB1/2 receptor-1 (compound 5.3) serves as an agonist for CB1/2 receptors and is utilized in angiogenesis research.</p>

<p>KF26777 is a potent and selective antagonist of adenosine A3 receptor.</p>

<p>TAK-637 is a tachykinin 1 (NK1) receptor antagonist.</p>

<p>PAR-2-IN-2 (compound P-596) is an inhibitor of protease-activated receptor 2 (PAR-2), with an IC50 of 10.79 μM for SLIGKV and an IC50 greater than 200 μM for trypsin.</p>

<p>Cendifensine functions as a monoamine reuptake inhibitor, targeting the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT).</p>

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

<p>Dopamine D4 receptor ligand 3 (Compound 16) functions as a dopamine D4 receptor (D4R) antagonist with a pKi of 8.86. In HEK-293T cells, it shows pIC50 values of 5.78, 5.55, and 6.17 for Go, Gi, and βArr2 sensors, respectively. This compound inhibits the activity of human glioma cell lines U87 MG, T98G, and U251 MG, and it induces ROS production and mitochondrial dysfunction in these glioma cells.</p>

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

<p>Tezosentan is an antagonist of the endothelin receptor (pA2s: 9.5, 7.7 for ETA and ETB receptors, respectively).</p>

<p>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.</p>

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

<p>LY210073 is an antagonist of the Leukotriene B4 (LTB4) receptor (IC50: 6.2 nM).</p>

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

<p>L-654284 is an α2-adrenergic receptor antagonist characterized by its notable selectivity. It competes with 3H-clonidine and 3H-rauwolscine for binding in vitro, exhibiting Ki values of 0.8 nM and 1.1 nM, respectively. L-654284 effectively blocks the pre-ejaculatory effects of clonidine in isolated rat vas deferens, with a pA2 value of 9.1. The compound demonstrates significant selectivity for α2 over α1 adrenergic receptors, with a Ki value of 110 nM against 3H-prazosin binding. In vivo, L-654284 significantly increases the turnover of norepinephrine in the rat cerebral cortex, indicating its activity in blocking α2-adrenergic receptors within the central nervous system.</p>

<p>Methacycline, a tetracycline antibiotic, inhibits bacterial protein synthesis and effectively suppresses epithelial-mesenchymal transition (EMT). It blocks EMT in vitro and inhibits fibrogenesis in vivo without directly affecting the TGF-β1Smad signaling pathway. As an antimicrobial agent, Methacycline holds potential for research in pulmonary fibrosis.</p>

<p>Nolpitantium besilate is a neurokinin-1 receptor antagonist.</p>

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

<p>Tebideutorexant, an orexin-1 receptor antagonist, shows anti-panic effects in rodents and humans, providing a tool for stress response and psychiatric research.</p>

<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>

<p>INCB-9471 HCl: a potent CCR5 antagonist, blocks monocyte migration &amp; HIV-1.</p>

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

<p>CP-865569 is a CCR1 antagonist useful in the research of inflammatory and autoimmune diseases, including conditions such as rheumatoid arthritis and multiple sclerosis.</p>

<p>EP3 and EP1 receptor agonist</p>

<p>Anthrotainin is a tetracyclic compound that acts as an inhibitor of the binding of P substance (substance P), with an IC50 of 3 μM.</p>

<p>Compound 21a: Oral GnRH-R antagonist, IC50=0.57 nM, potent against prostate cancer/prevents LH surges.</p>

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

<p>BI-113823 is an orally active and selective bradykinin B1 receptor antagonist. It alleviates mechanical hyperalgesia induced by complete Freund's adjuvant in rats. BI-113823 is applicable for research on chronic inflammatory pain.</p>

<p>5-HT6R/MAO-B modulator 1 blocks 5-HT6R and permanently inhibits MAO-B, protects glial cells, and reverses memory loss.</p>

<p>NK3 receptor antagonist</p>

<p>(R)-MrgprX2 antagonist-3 is an antagonist of MrgprX2. It is applicable in the study of inflammatory skin diseases. For more detailed information, please refer to compound E118 in patent document WO2021092240A1.</p>

<p>R-137696 is an orally active 5-HT1A receptor agonist that facilitates the relaxation of the proximal stomach. It is utilized in research related to functional dyspepsia.</p>

<p>Flucopride (Compound 4a) acts as an acetylcholinesterase inhibitor (AChE) with an IC50 value of 24 nM and serves as a partial agonist for the human 5-HT4 receptor (5-HT4R) with a Ki of 9.6 nM for (h)5-HT4R. It promotes non-amyloidogenic processing of APP in COS-7 cells transiently expressing (h)5-HT4R with an EC50 of 23.0 nM. Flucopride is also likely to exhibit significant gastrointestinal tract (GIT) penetration and blood-brain barrier (BBB) permeability, as determined in PAMPA experiments.</p>

<p>AGH-107 is a highly selective 5-HT7 receptor agonist that can cross the blood-brain barrier, featuring a Ki value of 6 nM and an EC50 value of 19 nM. Demonstrating high selectivity for central nervous system targets, AGH-107 also exhibits high metabolic stability and low toxicity in HEK-293 and HepG2 cell cultures.</p>

<p>Butaprost: EP2 receptor agonist, EC50=33 nM, Ki=2.4 μM (murine), reduces fibrosis via TGF-β/Smad2.</p>

<p>Potent 5-HT6/5-HT2A receptors dual antagonist with K i of 11 nM &amp; 39 nM.</p>

<p>PGD2 is involved in allergy, asthma, sleep, temperature regulation, inhibits clotting, and relaxes blood vessels; PGDM, its metabolite, is a biomarker.</p>

<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>

<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>

<p>Aclidinium, a dual-action compound, serves as a long-acting muscarinic antagonist and a β2-adrenoceptor (β2-AR) agonist, exhibiting bronchodilator properties. It effectively reduces lung hyperinflation, enhances lung function, and prolongs exercise endurance time. This compound is commonly utilized in studies focusing on chronic obstructive pulmonary disease (COPD).</p>

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

<p>AAZ-A 154 hydrochloride is a selective, competitive, non-hallucinogenic antagonist of 5-HT2AR. It promotes neuronal growth in rodents and results in enduring beneficial behavioral effects.</p>

<p>(S)-Butaprost (free acid) is a potent and highly selective EP2 receptor agonist[1].</p>

<p>RS 12254 is a dopamine agonist and antihypertensive agent.</p>

<p>FDU-PB-22, a novel synthetic cannabinoid, undergoes rapid metabolism in human liver microsomes (HLM) with a half-life of 12.4 minutes.</p>

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

<p>AA 497, a beta-2 agonist, causes relaxation and suppresses Ca spike frequency.</p>

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

<p>Y1 receptor antagonist 1 is an antagonist of neuropeptide Y1 receptor.</p>

<p>MRS2279 diammonium, a P2Y1 antagonist with K i 2.5 nM, IC 50 51.6 nM, blocks ADP-induced platelet aggregation, pK b 8.05.</p>

<p>Rodatristat is an effective tryptophan hydroxylase 1 and TPH2 inhibitor (IC50s: 33 nM and 7 nM, respectively).</p>

<p>AL 6598, a prodrug of PGD2 agonist AL 6556, reduces IOP by 53% at 1μg twice daily in monkeys; binds DP receptors with Ki of 3.2μM.</p>

<p>Nipradolol blocks alpha-1-adrenergic receptors, lowers IOP in rabbits, and reduces NA-induced muscle contraction and dog artery vasodilation.</p>

<p>Potent, oral MRGPRX1 agonist 4 modulates receptor positively (EC50: 0.1 μM) and reduces mice's thermal allergy response.</p>

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

<p>Compound 13 is a PAR-1 antagonist with a 3 nM IC50, useful for thrombosis and heart disease research.</p>

<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>

<p>EP4 receptor antagonist 2 (compound 2-13) is a potent agonist of the EP4 receptor (IC50: 7.8 nM) and has antitumour effects.</p>

<p>Serlopitant is a selective antagonist of Neurokinin-1 (NK-1) receptor.</p>

<p>MrgprX2 antagonist-7 is an anti-allergic agent with significant anti-allergic effects and inhibits mast cell degranulation.</p>

<p>MK-3207 Hydrochloride (MK-3207 HCl) is a potent CGRP receptor antagonist with IC50 and Kiof 0.12 nM and 0.022 nM, highly selective versus human AM1, AM2, CTR, and AMY3. Phase 2.</p>

<p>(1R,2S,3R)-Aprepitant (Compound ent-4) is a competitive antagonist of the human neurokinin-1 (NK-1) receptor. It holds potential for research in the treatment of nausea and vomiting related to cancer or postoperative conditions.</p>

<p>AH22921 is an EP4 prostaglandin receptor antagonist with the ability to antagonize the activation of adenylyl cyclase by prostaglandins in CHO cells. It induces a rightward shift in the PGE? concentration-response curve in these cells, functioning as a non-competitive antagonist. AH22921 is selective for the EP4 receptor, inhibiting its activity in CHO cells without affecting the PGE? concentration-response curve in NPE cells that contain the EP2 receptor.</p>

<p>Potent, oral SSTR5 antagonist 2 TFA may treat type 2 diabetes.</p>

<p>Toladryl is a derivative of Diphenhydramine that can cross the blood-brain barrier and exhibits oral activity, with antihistamine and anticholinergic properties. Its anticholinergic effects are approximately a tenth of those seen with Diphenhydramine, yet it offers 2-4 times the protection against lethal doses of histamine in guinea pigs. The side effects of Toladryl are fewer and milder compared to Diphenhydramine; however, at higher doses, it may cause symptoms such as insomnia, agitation, and disorientation related to the central nervous system. Toladryl is utilized in the research of allergic diseases.</p>

<p>CS-0777 is a potent, selective, and orally active S1P1 agonist (sphingosine 1-phosphate receptor modulator).</p>

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

<p>AZD5462 is a potent orally available relaxin receptor RXFP1 agonist for the study of heart failure and cancer.</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>Vofopitant (GR 205171) is a potent NK1 receptor antagonist with anxiolytic and antiemetic activity for the study of post-traumatic stress disorder (PTSD).</p>

<p>SB-224289 hydrochloride (SB-224289A) is a selective antagonist of 5-HT1B receptor, with anxiolytic effect.</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>AZD-5672 is an antagonist of CCR5 with an IC50 of 0.32 nM.</p>

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

<p>Dersimelagon (MT-7117) is an orally active, selective melanocortin 1 receptor (MC1R) agonist.Cost-effective and quality-assured.</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>PF-07258669 is a selective melanocortin 4 receptor (MC4) antagonist used in the study of cachexia and loss of appetite.</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>Rolapitant HCl is a potent NK1 antagonist, non-CYP3A4 interactive, with anti-emetic effects and a Ki of 0.66 nM.</p>

<p>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).</p>

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

<p>Metipranolol hydrochloride is a non-selective β-adrenergic receptor blocking agent.</p>

<p>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.</p>

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

<p>SB-399885 hydrochloride is an antagonist of 5-HT6 receptor.</p>

<p>(Rac)-Rotigotine hydrochloride is a racemate of Rotigotine. Rotigotine is a full agonist of dopamine receptor, a partial the 5-HT1A receptor agonist.</p>

<p>HOKU-81is a new bronchodilator and is one of the metabolites of tulobuterol.</p>

<p>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.</p>

<p>Beraprost sodium is a stable and orally active prodrug of PGI2.</p>

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

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

<p>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.</p>

<p>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.</p>

<p>SR 146131 is a potent and selective agonist of the nonpeptide receptor.</p>

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

<p>Atenolol (Tenormin) is a selective β1 receptor antagonist.</p>

<p>R(-)-alpha-Methylhistamine 2HCl is an effective and selective agonist of the H3 histamine receptor.</p>

<p>(Rac)-Zevaquenabant ((Rac)-MRI-1867, compound 6b) is a potent and selective antagonist of cannabinoid receptor type 1 (CB1R) and inducible nitric oxide synthase (iNOS), with a binding affinity (Ki) of 5.7 nM for CB1R. It holds promise as an investigative tool in liver fibrosis research due to these characteristics.</p>

<p>Propiram fumarate HClis an orally available Opioid receptors agonist with analgesic activity for the study of musculoskeletal pain.</p>

<p>Desmethyl cariprazine is a Cariprazine active metabolite. Cariprazine, an antipsychotic drug candidate, shows a high affinity for the D3 (Ki: 0.085 nM) and D2 (Ki: 0.49 nM) receptors, and moderate affinity for the 5-HT1A receptor (2.6 nM).</p>

<p>Sarizotan (EMD 128130) is an orally active compound that acts as an agonist for serotonin 5-HT 1A receptors and dopamine receptors, with IC50 values of 6.5 nM for rat 5-HT 1A, 0.1 nM for human 5-HT 1A, 15.1 nM for rat D 2, 17 nM for human D 2, 6.8 nM for human D 3, and 2.4 nM for human D 4.2.</p>

<p>Dapitant, a non-peptide, selective antagonist of human NKI receptors, is representative of the 7,7,4-triarylperhydroisoindol-4-ols.</p>