GPCR/G-Protein

Tarazepide is a potent and specific antagonist of CCK-A receptor.

RO5527239 is a potent, orally available GPBAR1 agonist agent.

L-772,405 is a highly selective agonists of h5-HT(1D) receptor.

PSB-SB1202 (Compound 21a), a phenyl coumarin compound, acts as a CB1/CB2 agonist. It demonstrates EC50 values of 56 and 14 nM and K i values of 32 and 49 nM for CB1 and CB2 receptors, respectively [1].

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

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

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].

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

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

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

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

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

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

<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>

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

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.

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

PD-140548 is a potent, CCKA receptor-selective antagonist.

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

BAY 73-1449 is a selective and potent antagonist of the prostacyclin receptor(IC50<0.1 nM).

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

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].

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

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

GLP-1R agonist 9 acts as a GLP-1R agonist, demonstrating efficacy with EC50 values of 1.1 nM and 11 nM against CHO GLP-1R Clone H6 and Clone C6, respectively.

IWP-051: potent oral sGC stimulator, >99% protein bound, stable, permeable, no Caco-2 efflux, potential for daily dose.

NAS-181 is a potent and selective rat 5-hydroxytryptamine 1B (r5-HT1B) antagonist (Ki: 47 nM).NAS-181 enhances the accumulation of 5-HTP in rat brain regions.

UNC9994 is a β-arrestin-biased dopamine D₂ receptor agonist (β-arrestin EC50 = 50 nM; Emax = 97%) with robust in vivo antipsychotic drug-like activities.

GR-127935 is a potent and selective 5-HT1B/1D receptor antagonist.

FAUC-312 is a potent and selective agonist of the dopamine D4 receptor.

Ritobegron is used as a selective β3-adrenoceptor agonist and the prodrug of the active compound, KUC-7322.

YM44778 is a NK1-receptor antagonist for treating restless legs syndrome.

BMS-763534 is a potent antagonist of corticotropin-releasing factor/hormone receptor 1 (CRHR-1).

<p>(S)-Renzapride (BRL 24924), 5-HT4 agonist (Ki 115 nM), 5HT2b/5HT3 antagonist, for C-IBS study.</p>

GP3269 is a selective, potent, orally active human adenosine kinase (AK) inhibitor (IC50: 11 nM) with anticonvulsant effects in rats.

<p>LY320954 is an antagonist of 5-HT2A receptor.</p>

Vemtoberant is a β3 adrenergic antagonist used in β3-related disorder research like heart failure.

<p>VKGILS-NH2 TFA, a non-impacting control peptide for PAR2 agonist SLIGKV-NH2, doesn't affect DNA synthesis.</p>

MRS3558 is an agonist of A3 adenosine receptors.

INT-777 is the R-enantiomer of INT-777, less potent than INT-777,EC50 of 4.79 μM for TGR5.

BMS-764459 is a potent antagonist of corticotropin-releasing factor/hormone receptor 1 (CRHR-1).

PSB-10 hydrochloride is a human adenosine A3 receptor antagonist.

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

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

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

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

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

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

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

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

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

<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>

Cipralisant maleate is a potent, selective Histamine H3 receptor antagonist.

Aganepag isopropyl can be used to treat Glaucoma.

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>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>

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

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.

GLP-1R agonist 10 is a GLP-1 agonist (EC50: 0.051 nM).

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

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.

Pecavaptan is a vasopressin receptor antagonist.

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

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

MK3577 is a glucagon receptor antagonist.

gonadotropin-releasing hormone (GnRH, LHRH) receptor antagonist,orally active

TASP0376377 is a potent antagonist of CRTH2.

GSK2263167 is an agonist of S1P1 receptor.

Lazuvapagon is a vasopressin V2 receptor agonist that can be used to study enuresis.

PD 165929 is a selective antagonist of Bombesin BB1.

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

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

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

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

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

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

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

FPPQ blocks 5-HT3 and 5-HT6 receptors (Ki: 0.9 & 3 nM) and may improve psychosis and cognition.

<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>

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

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

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

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

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

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].

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].

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

<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>RXFP1 receptor agonist-3 (Example 223) is an agonist of the RXFP1 receptor that inhibits cyclic AMP (cAMP) production in HEK293 cells stably expressing human</p>

Cis-J-113863 is a competitive antagonist for the chemokine receptor 1 (CCR1), demonstrating inhibitory concentration 50 (IC50) values of 0.9 nM for human CCR1 receptors and 5.8 nM for mouse CCR1 receptors, respectively [1].

Ginkgolic acid 2-phosphate, a potent sphingosine 1-phosphate (S1P) agonist, induces ERK phosphorylation and interacts with S1P1 [1].

ABT-702 hydrochloride effectively inhibits adenosine kinase, exhibiting an IC50 value of 1.7 nM [1] [2].

<p>Sigma-1 receptor antagonist 3 is a more potent and selective antagonist of Sigma-1 (σ1) receptor (Ki = 1.14 nM) than σ2 receptor(Ki = 1239 nM).</p>

<p>COR659: suppresses alcohol/chocolate intake in rats; enhances GABAB receptor, blocks CB1 receptor.</p>