GPCR/G-Protein

<p>SGL5213 is a potent oral SGLT1 inhibitor (IC50: 29 nM) with potential for treating type 2 diabetes.</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>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>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>CCR7-Cmp2105 is a thiadiazole-dioxide allosteric antagonist for CCR7 with a Kd of 3 nM and IC50 of 7.3 μM against arrestin binding.</p>

<p>Zaladenant is an adenosine receptor antagonist with antitumor properties.</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>INCB-9471 HCl: a potent CCR5 antagonist, blocks monocyte migration &amp; HIV-1.</p>

<p>Henagliflozin (SHR3824): an oral, selective SGLT2 inhibitor, weak on SGLT1.</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>TAAR1 agonist 2 (compound 30), a full agonist at trace amine-associated receptor 1 (TAAR1) (pEC50=7.5), also displays agonistic properties at H1 receptors and activates various muscarinic acetylcholine receptors, including the M2 receptor (pEC50=5). This compound is utilized in researching neuropsychiatric diseases.</p>

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

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

<p>5-HT2/5-HT7 receptor antagonist</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>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>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>Cicaprost (ZK 96480) is an IP agonist with artery relaxing effects; EC50 is 5.8 nM.</p>

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

<p>Taranabant: potent CB1 receptor inverse agonist; inhibits agonists with 0.13 nM Ki in vitro.</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>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>Terguride: treats hyperprolactinemia, blocks 5-HT2A/B, activates dopamine receptors, studied for PAH.</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>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>

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>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</p>

TAK-024 is an inhibitor of platelet(IC50s of 31, 79 and 51 nM in human, monkey and guinea pig, respectively).

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

<p>RF9 hydrochloride is a potent and selective Neuropeptide FF receptor antagonist that acts on hNPFF1R (Ki: 58 nM) and hNPFF2R (Ki: 7 nM).</p>

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

SB-423557 is an orally active antagonist of calcium-sensing receptor (CaR) with IC50 of 520 nM

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

<p>5-IAI hydrochloride is a psychoactive analog of para-iodoamphetamine. 5-IAI hydrochloride significantly reduces serotonin uptake sites and hippocampal serotonin levels in rats.</p>

<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>

<p>U75302 is an antagonist of thymosin beta-4 (TB4) receptor with a Ki value of 159 nM on guinea pig lung membranes.</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>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>

<p>Ro4368554 is a selective 5-HT6 antagonist capable of crossing the blood-brain barrier. It can reverse memory deficits caused by scopolamine and tryptophan depletion. Ro4368554 is applicable for research related to memory impairments.</p>

<p>5-HT2 receptor antagonist</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>S1PR1 agonist 1 is a potent agonist of S1PR1. S1PR1 agonist 1 has potential in autoimmune diseases.</p>

Ici D1542: potent TXS inhibitor & TXA2 receptor antagonist, effective thromboxane blocker in vitro.

<p>MDA7 is a selective agonist of the cannabinoid receptor 2 (CB2), demonstrating an EC50 of 128 nM in human CB2 receptors and 67.4 nM in rat CB2 receptors. The compound exhibits good affinity for CB2 receptors, with Ki values of 422 nM for humans and 238 nM for rats. In rat models, MDA7 shows analgesic activity.</p>

<p>Compound 23: H3R antagonist with 170 nM Ki; inhibits AChE, BChE, hMAO B; IC50s: 180, 880, 775 nM; anti-pain, memory boost; crosses BBB. [1]</p>

<p>H3R antagonist 5 (Compound 1b) is a selective inverse agonist of the histamine H3 receptor that can penetrate the blood-brain barrier, with an IC50 of 0.54 nM. It is applicable for research related to the central nervous system.</p>

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

<p>WIN 66306: Cyclic heptapeptide, blocks NK1/NK2 receptors, inhibits substance P-triggered contractions in guinea pig ileum.</p>

<p>8-iso PGF3α is an isoprostane produced from the free-radical peroxidation of EPA.</p>

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

<p>Compound 1f, a potent MRGPRX1 agonist, has an EC50 of 0.22 μM, useful for neuropathic pain studies.</p>

<p>ADORA2A/PDE4D-IN-1 (Compound 9) is a dual inhibitor of the adenosine A2a receptor (ADORA2A) and phosphodiesterase 4D (PDE4D). This compound is applicable for research in bronchial asthma.</p>

<p>GLP-1R agonist 8 is a potent agonist of GLP-1R (EC50 &lt; 2 nM).</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>Teoprolol is a blocker of β-adrenergic receptor.</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>LTD4 antagonist 1 is a potent and orally active antagonist of leukotriene D4 (LTD4; Ki: 0.57 nM).</p>

<p>Nolpitantium besilate is a neurokinin-1 receptor antagonist.</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>UK 432097 is an adenosine A2A agonist.</p>

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

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

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

<p>Merigolix is a potent gonadotrophin releasing hormone (GnRH) antagonist .</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>5-HT2A and 2C receptor antagonist</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>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>BIIE-0246: A potent, non-peptide Y2 receptor antagonist; &gt;650-fold more selective than Y1, Y4, Y5.</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>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>AL-8810 is an 11β-fluoro analog of PGF 2α with selective antagonist effects at the PGF 2α receptor (FP receptor) [1].</p>

<p>ZK118182 isopropyl ester is a PG analog with potent DP-agonist activity (EC50 = 16.5 nM) and high affinity for the DP receptor (Ki = 74 nM).</p>

<p>Potent D4R antagonist-2: selective, IC50=6.52 μM, good in vitro PK and brain penetration, potential for Parkinson's research.</p>

<p>SSR-241586: Neurokinin antagonist, treats depression, schizophrenia, urinary issues, emesis, IBS.</p>

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

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

<p>BAY-899, oral LH-R antagonist, IC50: 185 nM (hLH), 46 nM (rLH), lowers sex hormones in vivo.</p>

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

<p>BI 703704, a soluble guanylate cyclase (sGC) activator, inhibits the progression of diabetic nephropathy in the ZSF1 rat [1].</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>MrgprX2 antagonist-6 is a potent antiallergic agent with inhibitory effects on mast cell degranulation.</p>

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

<p>Vibegron (MK-4618) is an effective and selective Beta 3 adrenergic receptor agonist, used to treat overactive bladder (OAB).</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>PF-07054894: potent CCR6 antagonist, targets GPCR, for inflammatory bowel disease research.</p>

<p>(E/Z)-Ozagrel (sodium) [(E/Z)-OKY-046 (sodium)] is a mixture of the EZ isomers of Ozagrel (sodium). It acts as a thromboxane A2 (TXA2) synthase inhibitor. As an antiplatelet agent, Ozagrel (sodium) selectively inhibits human platelet aggregation, with an IC50 of 53.12 μM.</p>

<p>MK-8318 is an effective and selective antagonist of the CRTh2 receptor (Ki: 5.0 nM).</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>BMS-741672 is a potent, selective CCR2 antagonist for the treatment of neuropathic pain.</p>

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

<p>CCK2 (CCK-B) receptor antagonist</p>

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

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

<p>Nedocromil sodium is a pharmacologic stabilizer of mast cells, has been shown to normalize cytokine levels and attenuate cardiac remodeling.</p>

<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>

<p>L-97-1 is an antagonist of the adenosine A1 receptor.</p>

<p>CCR4 antagonist 2 (Compound 31) is a novel potent, orally bioavailable small molecule antagonists of CC chemokine receptor 4 (CCR4) that inhibits Treg</p>

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

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

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