GPCR/Proteína-G

<p>iso-TRAP-6 (iso-SFLLRN), a hexapeptide made from isoserine instead of serine, is a PAR1 agonist that activates platelets via PAR-1.</p>

<p>Neladenoson dalanate (BAY-1067197), an oral Adenosine A1 receptor partial agonist, is safe with good pharmacokinetics for chronic heart disease.</p>

<p>ACT-335827: oral, brain-penetrant OXR1 selective antagonist; IC50: 6 nM (OXR1), 417 nM (OXR2); for neurological research.</p>

<p>E-6123 is an antagonist of platelet-activating factor (PAF) receptor.</p>

<p>Compound 40, a cyclic Ape13 analogue and potent APJ agonist (Ki 5.7 nM), shows Gα12-bias and longer half-life.</p>

<p>LAS191859, a CRTH2 antagonist, IC50: 7.6-15.5nM across species, 21h half-life for sustained in vivo effect.</p>

<p>UCB-35440, a 5-lipoxygenase inhibitor and a histamine H1 receptor antagonist, is used potentially for the treatment of dermatitis.</p>

<p>11-Keto Fluprostenol, a potent analog of prostaglandin F2α (PGF2α), primarily interacts with the FP receptor. It is a structurally modified derivative of prostaglandin D2 (PGD2) designed to enhance its potency and extend its half-life. The compound is produced by oxidizing fluprostenol at the C-11 position, which results in 11-keto fluprostenol. This modification allows 11-keto Fluprostenol to exhibit moderate affinity for the CRTH2/DP2 receptor, though it shows negligible activity at the DP1 receptor, distinguishing its action from that of PGD2.</p>

<p>FR-181157, a novel prostaglandin (PG) mimetic, shows high potency and agonist efficacy at the IP receptor and has good bioavailability.</p>

<p>GRK2 Inhibitor 2 (Compound 8h), with an IC50 of 19 nM for GRK2 and 137 nM for Aurora-A, enhances β-AR-mediated cAMP accumulation in GRK2-overexpressing HEK293</p>

<p>DA-3934 targets gastrin/CCK-B receptors, not CCK-A, and reduces rat gastric acid secretion dose-dependently.</p>

<p>ONO-0740556 is a potent agonist of the Gi-coupled human lysophosphatidic acid receptor 1 (LPA1), exhibiting an EC50 value of 0.26 nM.</p>

<p>Potent oral APJ agonist (EC 50:0.4 nM); improves cardiac function in HF, with good pharmacokinetics and safety.</p>

<p>APJ receptor agonist 6 is a potent agonist of the APJ (apelin receptor) (Ki: 0.059 μM). (EC50: 6.22 μM).</p>

<p>Velusetrag(TD-5108), a potent 5-HT4 agonist, is in development for gastroparesis, constipation, and IBS.</p>

<p>2-Furoyl-LIGRLO-amide TFA is a potent and selective agonist of the proteinase-activated receptor 2 (PAR2), exhibiting a pD2 value of 7.0 [1] [2].</p>

<p>Abaperidone is an atypical antipsychotic, antagonizes 5-HT2A (IC50=6.2 nM) and D2 receptors (IC50=17 nM), reduces hsp70 mRNA in rat brains.</p>

<p>SC-50605 is a second-generation LTB4 receptor antagonist.</p>

<p>Cipralisant maleate is a potent, selective Histamine H3 receptor antagonist.</p>

<p>Aganepag isopropyl can be used to treat Glaucoma.</p>

<p>"YM543 is an effective, oral SGLT2 inhibitor that lowers blood glucose, useful for diabetes research."</p>

<p>ONO-2050297 is the first potent dual CysLT1 and CysLT2 antagonist with IC50 values of 0.017 μM (CysLT1) and 0.00087 μM (CysLT2), respectively.</p>

<p>GSK-554418A, a novel azaindole CB(2) agonists, is used for the treatment of chronic pain. It is efficacious in the acute model and the chronic joint pain model.</p>

<p>TC-SP 14 (compound 14) is a potent, orally available S1P1 agonist with EC50 of 0.042 μM; minimal S1P3 binding (EC50 3.47 μM); reduces blood lymphocytes.</p>

<p>TA-1887: Selective SGLT2 inhibitor, treats type 2 diabetes, lowers glucose in high-fat diet mice, boosts UGE, has good pharmacokinetics.</p>

<p>17-Phenyl trinor Prostaglandin F2αdiethyl amide (17-phenyl trinor PGF2αdiethyl amide) is a Prostaglandin F2α(PGF2α) analog characterized by the substitution of the C-1 carboxyl group with an N-diethyl amide. Prostaglandin (PG) esters and N-ethyl amides have demonstrated ocular hypotensive properties, with N-ethyl amides introduced as alternative options for PG hypotensive prodrugs. Studies indicate that both bovine and human corneal tissues can convert N-ethyl amides of various PGs into their free acid forms at a rate of approximately 2.5 µg/g corneal tissue/hr. However, dialkyl amides like 17-phenyl trinor PGF2αdiethyl amide resist conversion by corneal amidase, showing no detectable transformation into free acids. This characteristic suggests their potential as valuable investigative tools for assessing the intrinsic intraocular hypotensive activities of PG amides.</p>

<p>BAY 73-1449 is a selective and potent antagonist of the prostacyclin receptor(IC50&lt;0.1 nM).</p>

<p>GLP-1R agonist 10 is a GLP-1 agonist (EC50: 0.051 nM).</p>

[D-Ala6]-LH-RH, a Luteinizing-hormone-releasing hormone (LHRH) analogue, functions as a gonadotropin-releasing hormone (GnRH) receptor agonist [1].

<p>Satigrel is a new antiplatelet agent. It also inhibits platelet accumulation in prosthetic arterial grafts.</p>

<p>Compound 39, an APJ receptor agonist, has a K i of 0.6 nM, activates Gαi1 (EC50 0.8 nM), recruits β-arrestin2 (EC50 31 nM), and affects heart function.</p>

<p>Pecavaptan is a vasopressin receptor antagonist.</p>

<p>EX-1314 (BMS-604992) is a growth hormone secretagogue receptor (GHSR) agonist.</p>

<p>PD-140548 is a potent, CCKA receptor-selective antagonist.</p>

<p>S1P5 Receptor Agonist-1 (example 6) is a highly potent and selective agonist for the S1P5 receptor, exhibiting an EC50 value of 20 nM.</p>

<p>Frovatriptan, potent 5-HT 1B/D agonist, shows high cerebroselectivity and efficacy for migraine with aura.</p>

<p>AGN-191129 (PGF2α-OMe) is a PGF2α analog with C-1 carboxyl replaced by O-methyl; it lowers eye pressure, but its receptors are unclear.</p>

<p>MK3577 is a glucagon receptor antagonist.</p>

<p>gonadotropin-releasing hormone (GnRH, LHRH) receptor antagonist,orally active</p>

<p>TASP0376377 is a potent antagonist of CRTH2.</p>

<p>BIM 23056 TFA, a potent linear octapeptide antagonist of sst3 and sst5 somatostatin receptors, exhibits inhibition constants (K_i) of 10.8 for sst3 and 5.7 for</p>

<p>GSK2263167 is an agonist of S1P1 receptor.</p>

<p>Dihydrexidine is a full efficacy D1-like dopamine receptor (D1/D5) agonist (IC50: 10 nM for D1 receptor). It also shows potent antiparkinsonian activity.</p>

<p>(+)-Dihydrexidine hydrochloride is an agonist of dopamine D1 receptor(EC50 of 72± 21 nM).</p>

<p>Lazuvapagon is a vasopressin V2 receptor agonist that can be used to study enuresis.</p>

<p>PD 165929 is a selective antagonist of Bombesin BB1.</p>

<p>CP 154,526 is a selective CRF1 receptor antagonist (Ki = 2.7 nM). CP 154,526 blocks CRF-induced activation of adenylate cyclase and the HPA axis.</p>

<p>S1P5-selective agonist; less so for S1P1/S1P3; useful for CNS disorders.</p>

<p>NBI-35965 is a CRF1 receptor antagonist.</p>

<p>Indeloxazine HCl: Serotonin releaser, NE reuptake inhibitor, NMDA antagonist; antidepressant that boosts acetylcholine in rats.</p>

<p>γ-Linolenoyl monoethanolamide, a fatty N-acyl ethanolamine, acts as an endocannabinoid [1] [2].</p>

<p>Prostaglandin E1 (PGE1), though not predominantly found in nature, plays a significant role in clinical treatments, addressing conditions such as peripheral occlusive vascular disease, erectile dysfunction, and neonatal cardiology issues. The metabolism of PGE1 primarily begins with the oxidation at C-15, producing 13,14-dihydro-15-keto PGE1 as its major metabolite. Alternatively, inhibiting this pathway or overwhelming it with too much PGE1 could potentially enhance the production of 2,3-dinor metabolites, like 2,3-dinor PGE1, though their biological activities remain unreported. Cayman Chemical stands out as a prominent provider of prostaglandins and their metabolites, uniquely manufacturing 2,3-dinor PGE1.</p>

<p>Encaleret( JIT-305) is an antagonist of oral calcium-sensing receptor (CaSR), it is used for the treatment of osteoporosis.</p>

BAY 60-2770: oral sGC activator, NO-independent, antifibrotic, boosts sGC activity.

<p>(R)-Casopitant ((R)-GW679769), an NK1-receptor antagonist, is used in chemotherapy-induced nausea research.</p>

<p>SC 34301 (Enisoprost), a strong oral PGE1 analog, decreases bacterial translocation and increases burned mice survival.</p>

<p>LY3154885 is an orally active dopamine D1 receptor orthosteric modulator (PAM) that reduces the risk of drug-drug interactions (DDI).</p>

<p>RXFP1 receptor agonist-6 (Example 7) serves as an agonist for the RXFP1 receptor and effectively suppresses cAMP production in HEK293 cells that stably express</p>

<p>LM-1484 displays a higher affinity for 3H-LTC4 sites and is an antagonist of CysLT1 receptor.</p>

H3 receptor antagonist 1 is used in the study of neurological diseases, histamine H3 receptor antagonist.

GLP-1R agonist 12 (Compound 123) 是一种 GLP-1R 激动剂，能够用于研究糖尿病。

<p>FPPQ blocks 5-HT3 and 5-HT6 receptors (Ki: 0.9 &amp; 3 nM) and may improve psychosis and cognition.</p>

<p>Prostaglandin E2-1-glyceryl ester, a member of the Prostaglandin Glycerol Ester family, serves as an endocannabinoid ligand targeting the CB1 receptor. This compound triggers a swift and transient surge in intracellular free calcium levels [1] [2].</p>

<p>Prostaglandin K2 (PGK2), a 9,11-diketone derivative, results from PGE2 or PGD2 oxidation. Its biological presence remains speculative; however, it demonstrates resistance to in vitro metabolism by 15-hydroxy PGDH.</p>

<p>L 691678 is a potent leukotriene biosynthesis inhibitor.</p>

<p>SUCNR1-IN-1 (Compound 20) serves as a potent SUCNR1 inhibitor, exhibiting an IC50 of 88 nM against hSUCNR1.</p>

<p>MRS 1754 is a selective antagonist radioligand for the A2B adenosine receptor. It has a very low affinity for A1 and A3 receptors of both humans and rats.</p>

<p>Hedgehog IN-2 (Compound 20) functions as an inhibitor of the Hedgehog signaling pathway, exhibiting an IC50 of &lt;0.003 μM in C3H10T1/2 cells [1].</p>

<p>Orexin antagonist 4: potent, selective for OX2R (IC50=4.27 nM); less for OX1R (IC50=295 nM).</p>

<p>Heptadecanoyl ethanolamide, an endogenous cannabinoid, serves as a synthetic analog of PEA, featuring an odd-numbered (17-carbon) fatty acid chain [1].</p>

<p>RXFP1 receptor agonist-7 (Example 2) serves as an RXFP1 receptor agonist, effectively inhibiting cAMP production in HEK293 cells that stably express the human</p>

<p>Compound 39, or Y1R probe-1, is a fluorescent probe for Neuropeptide Y Y1 Receptor used in cancer research.</p>

<p>PSB-1115 potassium salt, a selective A2B Adenosine Receptor antagonist, inhibits the 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced contraction inhibition of acetylcholine (ACh) [1].</p>

<p>PF-03550096, an orally active synthetic cannabinoid (CB), selectively binds to peripheral CB2 receptors with a Ki value of 7.9 nM, demonstrating analgesic activity [1].</p>

<p>Velagliflozin proline hydrate, an oral SGLT2 inhibitor, reduces blood sugar by inhibiting renal glucose reabsorption.</p>

<p>Veldoreotide (DG3173) TFA, a somatostatin analogue, effectively binds to and activates somatostatin receptors (SSTR) 2, 4, and 5. This compound demonstrates a higher efficacy in inhibiting growth hormone (GH) secretion in adenomas than Octreotide, showcasing its potential as a pain modulating agent [1].</p>

<p>Quinpirole dihydrochloride is an agonist of the D2-like dopamine receptor.</p>

<p>Enerisant (TS-091) is a histamine H3 receptor antagonist that promotes pro-cognitive effects and reverses scopolamine-induced cognitive deficits.</p>

<p>Talibegron hydrochloride: β3 adrenoceptor agonist, pD2 3.72, relaxes rat arteries, reduces leptin in mice.</p>

<p>LGD-6972 is an antagonist of glucagon receptor.</p>

<p>Osemozotan is a 5-HT1A receptor agonist potentially for the treatment of generalized anxiety disorder.</p>

<p>(±)-Prenalterol (H 80/62) is an agonist of beta-2- and beta-1-adrenergic receptors and is used to study chronic congestive heart failure.</p>

<p>SAG 21k is an orally bioactive and potent Hedgehog signaling activator that crosses the blood-brain barrier for the study of cartilage regeneration.</p>

<p>GW 833972A: selective CB2 agonist; reduces neural depolarization and citric acid cough in animals.</p>

TAK-441: oral Hedgehog signal blocker, potent anticancer, IC50=4.4 nM, reduces Gli1 mRNA & tumor growth.

<p>α1 adrenoceptor-MO-1 (S enantiomer) has affinity at alpha 1 adrenergic receptor with alphalytic activity and analgesic action.</p>

<p>Adomeglivant (LY2409021) is a potent and selective glucagon receptor antagonist. Which is used in clinical trial for type 2 diabetes mellitus.</p>

<p>Lotiglipron (PF-07081532) is a GLP-1R agonist that lowers blood glucose and may be used in the study of type 2 diabetes mellitus (T2DM) and excess obesity.</p>

<p>WAY-639889 is a small molecule compound with selective and potent inhibitory effects on neuropeptide Y-5 receptors.</p>

<p>AY 77: Potent, selective PAR2 agonist, favors Ca2+ (ec50=40nM) &amp; ERK1/2 (ec50=2μM), boosts breast cancer cell migration.</p>

<p>K777: Oral cysteine protease inhibitor, CYP3A4 blocker (IC50=60 nM), CCR4 antagonist, anti-Trypanosoma cruzi, antiviral, halts EBOV/SARS-CoV entry (IC50&lt;1 nM).</p>

<p>GI 181771 is an agonist of the cholecystokinin 1 receptor. GI 181771 can be used in studies about obesity.</p>

<p>Ertugliflozin is a potent oral hSGLT2 inhibitor (IC50: 0.877 nM) for type 2 diabetes treatment studies.</p>

<p>Selvigaltin (GB1211) is a Gal-3 inhibitor with potential anticancer activity. Selvigaltin is used in the study of cirrhosis and cancer.</p>

<p>WAY-607695 is a potential 5-HT1A receptor agonist.</p>

<p>CGP-20712 is a selective β 1-adrenoceptor antagonist with an IC50 of 0.7 nM.</p>

dopamine D2 receptor modulator

<p>INT-777 (S-EMCA) is a potent TGR5 agonist with an EC50 of 0.82 μM.</p>

<p>SB 216641 hydrochloride (SB-216641A) is a 5-HT1B/D receptor antagonist with anxiolytic properties.</p>

0990CL is an effective heterotrimer Gαi subunit specific inhibitor, which can interact with purified Go± in GDP-bound state, and can block α2AR mediated cAMP