GPCR/Proteína-G

<p>U92016A hydrochloride: potent, orally active 5-HT1A agonist, metabolically stable, high intrinsic activity, Ki=0.2 nM.</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>L-365260 hemihydrate: selective oral CCK-B/gastrin blocker, Ki=1.9/2.0 nM, competes with guinea pig receptors.</p>

<p>CP-199330: non-toxic alternative to Zafirlukast &amp; Pranlukast, blocks cysteyl LT1 receptors.</p>

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

<p>THRX-194556 is an agonist of the 5-HT4 receptor. It is applicable in the study of gastrointestinal functional disorders and Alzheimer's disease.</p>

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

<p>hA3AR agonist 1 is a potent human A 3 adenosine receptor (hA 3 AR) agonist (Ki = 2.40 nM) .</p>

<p>(S)-Butaprost (free acid) is a potent and highly selective EP2 receptor agonist[1].</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>SGLT inhibitor-1 is a potentsodium glucose co-transporter proteins (SGLTs) dual inhibitor(hSGLT1 and hSGLT2 with IC50s of 43 nM and 9 nM, respectively).</p>

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

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

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

<p>Dopamine D 3 receptor ligand is a potent, selective, high-affinity dopamine D3 receptor ligand that is 89 times more selective for D3 (Ki: 8 nM) than D2 (Ki:</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>

PD 135158 is a CCK2 receptor antagonist.

<p>GRK6-IN-4 is an inhibitor of G protein-coupled receptor kinase 6 (GRK6) with an IC50 value of 1.56 μM. GRK6-IN-4 is applicable for research related to hematological malignancies, inflammatory diseases, and autoimmune disorders.</p>

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

<p>CBR Agonist-2: CB1 receptor agonist, EC50 - 960 nM, Ki - 970 nM, useful for hCB1R-related disease research.</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>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>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.</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>UMB24 is an effective antagonist of the σ2 receptor, exhibiting dissociation constants (Ki values) of 170 nM for the σ2 receptor and 322 nM for the σ1 receptor. This compound mitigates cocaine-induced convulsions and hyperactivity without causing mortality.</p>

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

<p>MDA77 is a CB2 agonist with an EC50 value of 5.82 nM and exhibits no activity towards CB1.</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>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>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>Iralukast is a cysteinyl-leukotriene antagonist (CysLT) with a pKi of 7.8 for CysLT1.</p>

<p>FR-145715 is a histamine H2 receptor antagonist characterized by its specific anti-Helicobacter pylori activity. This compound is utilized in the study of gastric lesions.</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>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>

<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>SEP-363856 (SEP-856) mesylate is an orally active compound that acts as an agonist for both TAAR1 and 5-HT1A receptors. This compound exhibits antipsychotic activity in the central nervous system and has potential for the study of schizophrenia.</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>5-HT6R/MAO-B modulator 1 blocks 5-HT6R and permanently inhibits MAO-B, protects glial cells, and reverses memory loss.</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>LY3154207: selective, potent oral human dopamine D1 receptor PAM, low agonist activity, EC50=3 nM.</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>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>A1 adenosine receptor antagonist</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>Elsovaptan is an antagonist of the vasopressin receptor and is applicable for research in Alzheimer's disease.</p>

<p>Sulamserod hydrochloride is a 5-HT4 receptor antagonist. It is utilized in research related to gastrointestinal disorders.</p>

<p>NK3 receptor antagonist</p>

<p>(Rac)-Nebivolol, a racemic β1-adrenergic blocker (IC50=0.8 nM), has vasodilatory properties and mitigates ethanol-induced cardiac harm.</p>

<p>5-HT7R antagonist 1 is a G protein-biased antagonist with Ki of 6.5 nM for 5-HT 7R.</p>

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

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

Macitentan n-butyl analogue, an oral ETA/ETB receptor blocker, may treat IPF and PAH.

<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>Tipelukast (KCA 757), an oral drug for asthma research, blocks leukotrienes and fights inflammation and fibrosis.</p>

<p>WIN 62577 is a species-selective tachykinin NK1 receptor antagonist and also serves as an allosteric enhancer with micromolar potency at M3 receptors. Additionally, WIN 62577 demonstrates potent antiviral activity against SARS-CoV-2.</p>

<p>CI-624 reduces the secretion and output of hydrogen ions, sodium ions, potassium ions, and pepsin. This compound may be utilized in research focusing on cancer and autoimmune diseases.</p>

<p>AFP 07 free acid is a 7,7-difluoroprostacyclin derivative. It also acts as a selective and highly potent agonist for the IP receptor.</p>

<p>(R)-BAY-899: R-isomer, selective LH-R antagonist, effective on hLH (IC50: 185 nM) and rLH (IC50: 46 nM), orally active.</p>

<p>Kendomycin is a proteasome inhibitor and endothelin receptor antagonist. It induces apoptosis in lymphoma.</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>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>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>Zaladenant is an adenosine receptor antagonist with antitumor properties.</p>

<p>CCR1 antagonist13 is a selective small molecule antagonist of CCR1.</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>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>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>LTD4 antagonist 1 is a potent and orally active antagonist of leukotriene D4 (LTD4; Ki: 0.57 nM).</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>Acyline, a GnRH antagonist, suppresses gonadotropins and testosterone in animals and maintains the effect for 2 weeks in men with one dose.</p>

<p>GAT564, an allosteric CB1R modulator, shows EC50s of 87 nM (cAMP) &amp; 320 nM (β-arrestin2) and lowers IOP effectively in glaucoma mice.</p>

<p>Compound 10 is a potent dual A1/A3 AR antagonist, with Ki values of 37.6 nM (hA1), 25.4 nM (hA3), and 1.47 nM (rA1), studied in renal, lung, and Alzheimer's.</p>

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

<p>DM-4111, one of the primary monohydroxy metabolites of Tolvaptan, is an effective vasopressin V2 receptor (vasopressin V2 receptor) inhibitor. By inhibiting water reabsorption in renal tubules, it facilitates the excretion of electrolyte-free water. DM-4111 holds potential for research in cardiovascular diseases.</p>

<p>PD 140376: Selective CCK-B/gastrin receptor antagonist radioligand for guinea pig stomach &amp; brain.</p>

<p>CHF-6366: M3 antagonist &amp; β2 agonist (pKi 10.4/11.4), mild Ca channel blocker, used in COPD study.</p>

<p>Cloprostenol is a synthetic prostaglandin and PGF2α analogue used in animals to terminate pregnancy and induce corpus luteum dissolution.</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>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>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>ONO-9780307 is a specific antagonist of LPA1 (lysophosphatidic acid receptor 1) (IC50: 2.7 nM).</p>

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

<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>

<p>Selective, high affinity competitive antagonist of the P2Y1 receptor</p>

<p>Taprostene (CG-4203), a stable Prostacyclin analogue, protects endothelium and myocardium post-ischemia in cats, with minimal hemodynamic impact.</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>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>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>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>OP-2507, a prostacyclin agonist, is used potentially for the treatment of hepatic insufficiency and hypertension.</p>

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

<p>5-HT1A modulator 4 (Compound 1) is a ligand for the 5-HT receptor, with Ki values of 2.18 μM for 5-HT1A and 19.7 μM for 5-HT2A.</p>

<p>SB 224289: selective 5-HT1B antagonist, pKi 8.2, 60x selectivity, effective orally.</p>

<p>UK 432097 is an adenosine A2A agonist.</p>

<p>VGD071, a compound that targets sortilin, presents a promising avenue for forthcoming research utilizing mouse models of breast cancer.</p>

<p>LPA2 antagonist 3 (compound 15) serves as an Lp(a) antagonist. Lp(a) is a pathogenic risk factor for atherosclerotic cardiovascular disease (ASCVD).</p>

<p>H1R ligand-1 (Compound fragment 1) is a high-affinity ligand for the human histamine H1 receptor (H1R). It can serve as a scaffold for synthesizing a series of derivatives to investigate H1R binding kinetics.</p>