Proteina G/GPCR

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

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

<p>PF-9404C: S-S diastereoisomer, beta-blocker with vasodilation, boosts cyclic GMP in rat aorta cells from 3 to 53 pmol/mg protein.</p>

<p>BRD50837 is a potent and selective inhibitor of Sonic Hedgehog (Shh).</p>

<p>CBR Agonist-1 targets CB1R and CB2R with Ki of 0.18 μM and 1.22 μM, useful for studying cannabinoid-related diseases.</p>

<p>PF-4693627 is an effective and selective microsomal prostaglandin E synthase-1 inhibitor (IC50=3 nM).</p>

<p>Selective oral S1P1 agonist 5 inhibits lymphocyte drainage, potential for MS research.</p>

<p>TGR5 Receptor Agonist 3 is a GPBAR1 agonist with EC50 of 16.4 nM (hTGR5) &amp; 209 nM (mTGR5), ensures gallbladder safety and reduces filling.</p>

<p>LPA2 antagonist 5 (EX1) functions as an antagonist of LPA2, with an IC50 value of 4.05 nM.</p>

<p>BNS808 is an orally active, selective CB1R antagonist with an IC50 of 0.8 nM, demonstrating significant selectivity for CB2R and minimal brain penetration. It is being studied for the treatment of obesity and related metabolic complications, such as metabolic dysfunction-associated steatotic liver disease (MASLD). BNS808 reduces drug exposure to the central nervous system, enhancing safety, and minimizes drug interactions through high plasma protein binding.</p>

<p>CP 481715 is an effective selective CCR1 antagonist with potential therapeutic significance for inflammatory diseases.</p>

<p>U92016A hydrochloride: potent, orally active 5-HT1A agonist, metabolically stable, high intrinsic activity, Ki=0.2 nM.</p>

<p>ONO-9780307 is a specific antagonist of LPA1 (lysophosphatidic acid receptor 1) (IC50: 2.7 nM).</p>

<p>RTIOXA-43 is an OX2R/OX1R (orexin receptor) dual agonist that increases wakefulnesand is commonly used in studies related to narcolepsy and neural signaling.</p>

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

<p>Cloprostenol is a synthetic prostaglandin and PGF2α analogue used in animals to terminate pregnancy and induce corpus luteum dissolution.</p>

<p>SB 258741 hydrochloride is a potent antagonist of the 5-HT 7 receptor, designed specifically for studying schizophrenia [1].</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>IRL 2500 is an antagonist of Endothelin receptor with IC50s of 1.3 and 94 nM for Endothelin A receptor and Endothelin B receptor.</p>

<p>S1P1 agonist 4 exhibits enhanced potency with an EC 50 value of less than 0.05 mg/kg and a predicted human half-life (t1/2) of approximately 5 days, indicating</p>

<p>EP4 receptor antagonist 7 (Compound 14) is an antagonist of the prostaglandin E2 (PGE2) receptor subtype EP4, with an IC50 of 1.1 nM. This compound inhibits PGE2-induced β-arrestin recruitment in HEK293 cells with an IC50 of 0.9 nM. In RAW 264.7 macrophages, it reduces the expression of PGE2-induced IL-4, macrophage mannose receptor 1 (Mrc1), chitinase-like protein 3 (Chil3), chemokine (C-X-C motif) ligand 1 (Cxcl1), triggering receptor expressed on myeloid cells 2 (Trem2), and arginase 1 (Arg1) mRNA. In the CT26 mouse colon cancer model, EP4 receptor antagonist 7, combined with an anti-PD-1 antibody, inhibits tumor growth and enhances CD8+ T cell infiltration into the tumor.</p>

<p>APJ receptor agonist 3 is a highly effective and orally administerable agonist of the APJ receptor, demonstrating a potent EC50 value of 0.027 nM.</p>

<p>LP 12 hydrochloride hydrate: potent, selective 5-HT7 agonist (Ki: 0.13 nM); less affinity for D2, 5-HT1A/2A receptors.</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>Taranabant: potent CB1 receptor inverse agonist; inhibits agonists with 0.13 nM Ki in vitro.</p>

<p>PD 135158 is a CCK2 receptor antagonist.</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-3207 is a potent, oral CGRP receptor antagonist with high selectivity for human and monkey receptors, inhibiting blood flow in vivo.</p>

<p>Compound 18g, a potent A1AR blocker with Ki: 2.08 nM (hA1), 6.91 nM (hA2A), 31.2 nM (hA2B).</p>

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

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

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

<p>TAK-075 is an orally active CaSR antagonist with an IC50 value of 0.94 nM. It transiently stimulates parathyroid hormone (PTH) secretion in rats and effectively prevents significant reduction in PTH secretion due to the accumulation of active metabolites, thereby maintaining a normal secretion pattern. TAK-075 is applicable in research related to metabolic diseases and osteoporosis.</p>

<p>AM9405: peripheral CB1/5-HT3 agonist, suppresses gut motility, relieves GI disorder symptoms in mice.</p>

<p>CCR5 antagonist 1 is a CCR5 antagonist extracted from WO 2004054974 A2. It can inhibit HIV replication.</p>

<p>Gemilukast (ONO-6950) is a cysteinyl leukotriene 1 and 2 receptor inhibitor that inhibits bronchoconstriction and is used in the treatment of asthma.</p>

<p>BI 639667, an azaindazole-class compound, potently inhibits CCR1 (IC50=1.8 nM in calcium flux assays).</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>A2A receptor antagonist 2 is a highly selective and potent antagonist of the adenosine A2Areceptor (IC50: 8.3 nM).</p>

<p>LTF4, made in vitro from LTE4 with enzymes, contracts vascular muscle weakly; potency is LTD4 &gt; LTC4 &gt; LTE4 &gt;&gt; LTF4.</p>

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

<p>Burapitant (SSR 240600) is a novel non-peptide tachykinin neurokinin 1 (NK) receptor antagonist with anti-coke oven and antidepressant activity.</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>BI 703704, a soluble guanylate cyclase (sGC) activator, inhibits the progression of diabetic nephropathy in the ZSF1 rat [1].</p>

<p>Revexepride, a 5-HT4 agonist, may boost CYP3A4, used for treating GERD.</p>

<p>NMDAR antagonist 5 (Compound A17) is a multi-target antagonist that acts on NMDAR and monoamine transporters (SERT, DAT, and NET). It demonstrates strong NMDAR antagonistic efficacy (IC50= 0.3 μM) and effective activity on monoamine transporters (SERT IC50= 1.1 μM, DAT IC50= 0.7 μM, NET IC50= 2.7 μM). NMDAR antagonist 5 exhibits high safety with low toxicity (hepatic and renal toxicity IC50&gt; 100 μM; cardiac toxicity IC50= 24.5 μM). It has antidepressant properties and is useful for depression research.</p>

<p>TAK-661 is an inhibitor of eosinophil chemotaxis (eosinophil chemotaxis) that significantly alleviates late-phase bronchoconstriction while inhibiting the proliferation of eosinophils in bronchoalveolar lavage (BAL) and their infiltration into the airway walls.</p>

<p>OP-2507, a prostacyclin agonist, is used potentially for the treatment of hepatic insufficiency and hypertension.</p>

<p>MED 27 is an inhibitor of thromboxane synthase and thromboxane A2 receptors. It effectively inhibits rat platelet aggregation at doses significantly lower than those required for acetylsalicylic acid.</p>

<p>L-657926 is a stereoselective antagonist of the thromboxane A2 (TxA2) receptor, composed of (-)-9-chlorobenzyl-6-fluoro-1,2,3,4-tetrahydrocarbazol-1-yl acetic acid and (+)-9-chlorobenzyl-6-fluoro-1,2,3,4-tetrahydrocarbazol-1-yl acetic acid. The IC50 values for the (-) and (+) configurations against TxA2 are 0.27 nM and 124 nM, respectively.</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>INCB-9471 HCl: a potent CCR5 antagonist, blocks monocyte migration &amp; HIV-1.</p>

<p>EP3 and EP1 receptor agonist</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>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>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>Zaladenant is an adenosine receptor antagonist with antitumor properties.</p>

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

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

<p>(Rac)-BI 703704 is a potent activator of soluble guanylyl cyclase (sGC).</p>

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

<p>D3/5-HT receptor modulator-1 (compound 5i) is a selective antagonist of the dopamine D3 and 5-HT2A receptors, and a partial agonist at the 5-HT1A receptor. It exhibits Ki values of 4.5 nM, 11.9 nM, and 15.3 nM for the dopamine D3, 5-HT2A, and 5-HT1A receptors respectively. The compound shows lower affinity for the dopamine D2 receptor, 5-HT2C receptor, and hERG channel. D3/5-HT receptor modulator-1 possesses atypical antipsychotic properties.</p>

<p>25B-NBOH hydrochloride is a phenethylamine that exhibits high affinity for serotonin (5-HT) receptors 5-HT2A and 5-HT2C, with pKi values of 8.3 and 9.4, respectively.</p>

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

<p>LY3154207: selective, potent oral human dopamine D1 receptor PAM, low agonist activity, EC50=3 nM.</p>

<p>Abarelix acetate: synthetic GnRHR antagonist, spikes histamine, lowers LH and testosterone temporarily, used in advanced prostate cancer.</p>

<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.</p>

<p>UR-AK49 (compound 11) is an agonist for the human histamine H1 and H2 receptors. It exhibits an EC50 of 23 nM in the GTPase assay involving hH2R-Gsalpha fusion protein expressed in Sf9 insect cells. UR-AK49 is applicable in neurologically related research.</p>

<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].</p>

<p>Aplaviroc, a potent CCR5 inhibitor, binds selectively, blocking HIV entry and specific monoclonal antibody attachment in vitro.</p>

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

<p>Compound 25l, also known as P2Y14R antagonist 4, is an orally active antagonist of the P2Y14R receptor with an IC50 of 5.6 nM. It exhibits higher binding affinity for P2Y14R compared to other PPTN receptors. P2Y14R antagonist 4 also possesses anti-inflammatory properties, reducing the release of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) induced by LPS.</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>AAZ-A 154 benzoate is a selective, competitive, and non-hallucinogenic 5-HT2AR antagonist. This compound facilitates neuronal growth in rodents and produces lasting beneficial behavioral effects.</p>

<p>Dopamine D3 receptor antagonist-2 is a dopamine D3 receptor selective (Ki=2.16 nM) or multi-targeting dual ligand that shows potential effects in CNS disorders.</p>

<p>PAR-1 antagonist 3: potent (IC50: 7 nM), binds hERG K+ channels (IC50: 9 μM).</p>

<p>YM-31636 (free base) is an orally active, potent, and selective agonist of the 5-HT3 receptor with a pKi value of 9.67. This compound induces contraction in isolated guinea pig distal colon and provokes tachycardia in isolated guinea pig right atrium, demonstrating a relative intrinsic activity of about 0.23. YM-31636 (free base) holds potential for research in constipation management.</p>

<p>MRGPRX2 modulator-1 (example 17), a modulator of the mas-related G-protein receptor X2 (MRGPRX2), is employed in studies focused on inflammation, pain, and autoimmune disorders [1].</p>

<p>KMN-80 is a potent, selective EP4 agonist with IC50 3 nM, spurring osteoblast differentiation, and showing in vivo bone repair efficacy.</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>GRK6-IN-5 is an inhibitor of the GRK6 polypeptide, with an IC50 of 4.48 μM. GRK6-IN-5 is utilized in research focused on hematological malignancies, inflammatory diseases, and autoimmune disorders.</p>

<p>Mrgx2 antagonist-3 (Compound B-40) is a highly selective antagonist of the MrgX2 receptor, with an IC50 range of 0.042-2.5 nM. It blocks downstream G protein signaling and β-arrestin recruitment, inhibiting Mrgx2 receptor-mediated calcium influx and cell degranulation. Mrgx2 antagonist-3 shows potential for research in inflammation-associated diseases and pruritus, such as chronic urticaria and allergic asthma.</p>

<p>SR2640 is a potent and highly selective LTD4/LTE4 antagonist, specifically inhibiting LTD4-induced contractions in guinea pig ileum and tracheal smooth muscle in a concentration-dependent manner, without affecting histamine-induced contractions. It blocks the binding of 0.4 nM [3H]LTD4 to guinea pig lung membrane receptors with an IC50 of 23 nM. SR2640 also causes a parallel rightward shift in the dose-response curve for LTD4-induced bronchoconstriction in guinea pigs when administered intravenously, with the degree of shift correlating positively with its dosage. SR2640 is applicable for asthma research.</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>Vofopitant dihydrochloride (GR 205171A) is a tachykinin NK1 receptor antagonist and a potential compound for the treatment of pathologic vomiting.</p>

<p>SB-423562 is a calcium-sensing receptor (CaSR) antagonist and can be used in studies about osteoporosis.</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>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>Dersimelagon (MT-7117) is an orally active, selective melanocortin 1 receptor (MC1R) agonist.Cost-effective and quality-assured.</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>AZD-5672 is an antagonist of CCR5 with an IC50 of 0.32 nM.</p>

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

<p>AZD5462 is a potent orally available relaxin receptor RXFP1 agonist for the study of heart failure and cancer.</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>BQ-788 is an ETB receptor antagonist with potential hypertensive activity that inhibits exogenous ET-1-induced elevation of coronary perfusion pressure.</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>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>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>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>