GPCR/Proteína-G

<p>L 668750 is an inhibitor of platelet-activating factor.</p>

<p>Compound (−)-19, also known as (-)-5-HT2C agonist-3, is a selective 5-HT2C agonist exhibiting a preference for Gq signaling. It demonstrates efficiency with EC50 values for 5-HT2 receptor subtypes as follows: 5-HT2C at 103 nM, 5-HT2B at 570 nM, and 5-HT2A at 72 nM. This compound is utilized in research on antipsychotics.</p>

<p>A3AR antagonist 5 (Compound 16) acts as a selective antagonist for the human adenosine A3 receptor (human adenosine A3 receptor), with an affinity expressed as a pC value of 4.542 μM.</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>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>Beloxepin is an oral dual selective inhibitor of serotonin and norepinephrine uptake.</p>

<p>P2Y2 and P2Y4 receptor agonist</p>

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

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

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

<p>PAR4 antagonist3 (Compound 36) is a selective antagonist of protease-activated receptor 4 (PAR4). It exhibits antiplatelet activity with an IC50 of 26.1 nM and enhances metabolic stability in human liver microsomes, with a half-life (T1/2) of 97.6 minutes.</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>CS-003: Triple neurokinin receptor antagonist; Ki=2.3 nM (NK1), 0.54 nM (NK2), 0.74 nM (NK3); treats respiratory diseases.</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>Burapitant (SSR 240600) is a novel non-peptide tachykinin neurokinin 1 (NK) receptor antagonist with anti-coke oven and antidepressant activity.</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>Compound 10o, a histamine H3 antagonist-1, functions as both a histamine H3 antagonist and a serotonin reuptake inhibitor, making it useful for research in depression [1].</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>Neladenoson is an effective and selective agonist of the Adenosine A1 Receptor (A1R). EGFR-IN-162 shows potential for research in heart failure.</p>

<p>ASN-1377642 is an NK1 receptor antagonist with a Ki value of 251 nM. It demonstrates antitumor activity in breast cancer cells with high expression of NK1R-Tr.</p>

<p>HU 433, a synthetic cannabinoid, acts as a CB2 receptor agonist and is an enantiomer of HU 308. It provides anti-inflammatory and neuroprotective effects by binding to the CB2 receptor, primarily found on immune cells, thereby modulating immune responses and inflammation. Additionally, HU 433 influences microglial signaling pathways, particularly LPS and IFNγ-mediated routes, affecting the phosphorylation of MAPKs, including ERK1/2, JNK, p38, and Akt. This compound is valuable in researching neuroinflammation and retinal diseases.</p>

<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</p>

<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>

<p>CVN766 is an orally active orexin 1 receptor antagonist with blood-brain permeability, demonstrating IC50 values of 8 nM for OX1R and &gt;10 μM for OX2R. CVN766 can be used to study schizophrenia [1].</p>

<p>SJPYT-310 is a selective PXR antagonist, exhibiting no noticeable cytotoxicity.</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>Acyline, a GnRH antagonist, suppresses gonadotropins and testosterone in animals and maintains the effect for 2 weeks in men with one dose.</p>

<p>Compound 2o, also known as CB2R/5-HT1AR agonist 1, serves as a partial orally active agonist for the CB2 receptor (EC50 = 479.6 nM) and a full agonist for the 5-HT1A receptor (EC50 = 2.7 μM). This compound demonstrates both anti-anxiety and anti-depressive effects and has favorable pharmacokinetic properties [1].</p>

<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>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>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>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>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>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>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>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>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>Compound 13 is a PAR-1 antagonist with a 3 nM IC50, useful for thrombosis and heart disease research.</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>GPR27 agonist-1 (compound I) is a selective agonist for GPR27 with a pEC50 value of 6.34.</p>

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

<p>Befiradol HCl (NLX-112) is a selective 5-HT1A receptor agonist with anxiolytic effects and prevents ATXN3 aggregation.</p>

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

<p>H3R-IN-1 is an effective inverse agonist of the histamine receptor 3 (H3R).</p>

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

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

<p>TAAR1 agonist 3 is a potent agonist of Trace Amine-Associated Receptor 1 (TAAR1) with a pEC50 value of 7.6. Additionally, it acts as a full agonist at the α2AR with a pEC50 of 6. TAAR1 agonist 3 is utilized in the research of neuropsychiatric disorders.</p>

<p>AFP-07 is a highly selective and potent agonist. It was used for the prostacyclin receptor.</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>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>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>Cicaprost (ZK 96480) is an IP agonist with artery relaxing effects; EC50 is 5.8 nM.</p>

<p>Oral CCR1 antagonist A1B1 targets h/m/rCCR1 (IC50: 0.03/0.58/0.32 μM), potential for treating inflammatory diseases.</p>

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

<p>YGZ-331, a sedative hypnotic, acts by elevating GABA levels as a derivative of the adenosine nucleoside NGBA. It functions through activating A1R and A2aR, and inhibiting the phosphorylation of CaMKII (pCaMKII), thereby exerting its calming effects. Additionally, YGZ-331 reduces spontaneous motor activity in mice.</p>

<p>VA012 (compound 11) acts as a positive allosteric modulator (PAM) of the serotonin 5-HT2C receptor. It has been shown to reduce food intake and prevent weight gain during subchronic administration without causing central nervous system-related discomfort. VA012 is applicable in obesity research.</p>

<p>Taranabant: potent CB1 receptor inverse agonist; inhibits agonists with 0.13 nM Ki in vitro.</p>

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

<p>RGS10 modulator-1 (compound 15) is an effective regulator of RGS10. It significantly reverses IFNγ-induced expression of both RGS10 protein and mRNA, as well as COX-2 mRNA and iNOS expression triggered by IFNγ.</p>

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

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

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

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

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

(S)-Bucindolol is an enantiomer of bucindolol, specifically a β1-adrenergic receptor antagonist. It is primarily utilized in research related to heart failure.

<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>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>Etoperidone is an antidepressant that acts as an orally active reuptake inhibitor for serotonin (serotonin) and noradrenaline (nor-adrenaline). It demonstrates specific binding affinities (Kd) for several receptors: 36 nM at the 5-HT2 receptor, 38 nM at the α1-adrenergic receptor (α1-adrenergic receptor), 85 nM at the 5-HT1A receptor, and 570 nM at the α2-adrenergic receptor (α2-adrenergic receptor).</p>

<p>Pareptide monohydrochloride is a metabolically stable analog of melatonin inhibitor (MIF).</p>

<p>ASP-2205, a 5-HT2C receptor agonist (human 5-HT2C receptor, EC50=0.85 nM; rat 5-HT2C receptor, EC50=2.5 nM), enhances the urethral closure reflex mediated by the genital nerve, thereby preventing urinary incontinence.</p>

<p>IMP-1575 is a highly effective inhibitor of hedgehog acyltransferase (HHAT), with an IC50 of 0.75 μM when inhibiting purified HHAT. IMP-1575 has potential applications in cancer research.</p>

<p>RU 52583 is an alpha 2-adrenergic receptor antagonist.</p>

<p>Neflumozide (HRP 913) is an orally effective derivative of benzisoxazole, characterized by its potent dopamine antagonist properties and antipsychotic activity. It is utilized in research related to psychiatric disorders.</p>

<p>Sigma-2 Radioligand 2 (compound 4) exhibits low nanomolar affinity for the σ2 receptor (Ki=2.30 nM) and high subtype selectivity (Ki(σ1)/Ki(σ2) &gt; 1500).</p>

<p>Mafoprazine, a phenylpiperazine derivative, exhibits varying affinities for neuronal receptors, primarily exerting its antipsychotic effects through blocking D2 receptors and enhancing α-adrenergic activity. It also increases the activity of dopamine metabolites.</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>F 14679 is a potent 5-HT1A agonist (pKi=10.23) with a maximum Ca2t response similar to 5-HT.</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>GnRH antagonist 2 is a GnRH receptor antagonist, useful for studying endocrine diseases.</p>

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

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

<p>K-8794 is an orally active and selective endothelin receptor ETB antagonist that can be utilized in cardiovascular disease research.</p>

<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>

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

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

<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>AMG-369 (AMG 247) is an S1P1/S1P5 dual agonist that delays the development of experimental autoimmune encephalomyelitis in rats.</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>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>

<p>PF-07258669 is a selective melanocortin 4 receptor (MC4) antagonist used in the study of cachexia and loss of appetite.</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>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>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>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>SB-423562 is a calcium-sensing receptor (CaSR) antagonist and can be used in studies about osteoporosis.</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>Dersimelagon (MT-7117) is an orally active, selective melanocortin 1 receptor (MC1R) agonist.Cost-effective and quality-assured.</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>Rolapitant HCl is a potent NK1 antagonist, non-CYP3A4 interactive, with anti-emetic effects and a Ki of 0.66 nM.</p>