G-protein Coupled Receptors and 7-TM Receptors

Enprostil: synthetic PGE2 analog, reduces gastric acid, protects mucosa, lowers post-meal gastrin, treats ulcers effectively and safely.

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.

KF26777 is a potent and selective antagonist of adenosine A3 receptor.

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

AA 497, a beta-2 agonist, causes relaxation and suppresses Ca spike frequency.

UK 432097 is an adenosine A2A agonist.

AL 6598, a prodrug of PGD2 agonist AL 6556, reduces IOP by 53% at 1μg twice daily in monkeys; binds DP receptors with Ki of 3.2μM.

<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>

CCR5 antagonist 1 is a CCR5 antagonist extracted from WO 2004054974 A2. It can inhibit HIV replication.

<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>

L-97-1 is an antagonist of the adenosine A1 receptor.

<p>Sigma-1 receptor antagonist 6 (Compound 12), a σ1R antagonist, demonstrates significant antiallodynic effects by targeting the Sigma-1 receptor (σ1R). This compound is effective in animal models for neuropathic pain, particularly for reducing mechanical allodynia caused by paclitaxel.</p>

MK-0812 is a dual antagonist of the CCR2 and CCR5 receptors that can alleviate adipose inflammation in ob/ob mice.

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

Kendomycin is a proteasome inhibitor and endothelin receptor antagonist. It induces apoptosis in lymphoma.

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

<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>

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

Pexacerfont (BMS-562086) is a selective antagonist of the corticotropin-releasing factor receptor (IC50: 6.1±0.6 nM for the human CRF1 receptor).

Potent CB1/2 agonist 1; crosses blood-brain barrier; anti-inflammatory, analgesic; for multiple sclerosis research.

Remlifanserin is a potent inverse agonist of the serotonin receptor (5-HT2A).

CS-003: Triple neurokinin receptor antagonist; Ki=2.3 nM (NK1), 0.54 nM (NK2), 0.74 nM (NK3); treats respiratory diseases.

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

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

GPBAR1-IN-3 (Compound 14) is both a selective agonist for GPBAR1, with an EC50 value of 0.17 μM, and an antagonist for CysLT1R [1].

Udifitimod (BMS-986166) is a potent, selective, and orally active modulator of the S1P1R receptor, showing potential for research in autoimmune diseases.

Disulergine is a dopamine receptor agonist. It also prolactin release-inhibiting 8 alpha-amino-ergoline.

RS 61756-007 is a selective thromboxane receptor (TP) agonist.

A1 adenosine receptor antagonist

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

SGLT1/2-IN-1 is a dual SGLT1/SGLT2 inhibitor.

GLP-1 receptor agonist 15 (Example 4) is a GLP receptor agonist with an EC50 of 0.74 nM. It exhibits an IC50 of 10.1 μM against the hERG potassium ion channel. This compound is applicable for research in the diabetes field.

Ro 24-4736 is an effective and selective platelet-activating factor antagonist.

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

Bzo-poxizid is a synthetic cannabinoid and a psychoactive substance.

RS 12254 is a dopamine agonist and antihypertensive agent.

Dopamine D3 receptor antagonist-2 is a dopamine D3 receptor selective (Ki=2.16 nM) or multi-targeting dual ligand that shows potential effects in CNS disorders.

Selective, orally active PAR-1 antagonist with an IC50 of 7 nM, potential for cardiovascular disease studies.

SAR-150640, a selective β3-adrenergic receptor agonist, prevents an increase in MMP activity and production observed after LPS stimulation or in cases of chorioamnionitis.

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.

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>H-Glu-Thr-OH (L-α-Glutamyl-L-threonine) is a dipeptide composed of two amino acids—glutamic acid (Glu) and threonine (Thr)—linked by a peptide bond and functions as an agonist of the extracellular calcium-sensing receptor (CaSR).</p>

<p>Inupadenant (EOS-850) is a selective A2a receptor antagonist, targeting immunosuppression in tumors.</p>

PF-07054894: potent CCR6 antagonist, targets GPCR, for inflammatory bowel disease research.

EP4 receptor antagonist 2 (compound 2-13) is a potent agonist of the EP4 receptor (IC50: 7.8 nM) and has antitumour effects.

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

<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>

Tiprenolol hydrochloride is a β-adrenoceptor (β-adrenoceptor) antagonist. This compound is effective in eliminating ventricular arrhythmias in dogs caused by intravenous administration of adrenaline, following inhalation of halothane.

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.

CB1/2 receptor-1 (compound 5.3) serves as an agonist for CB1/2 receptors and is utilized in angiogenesis research.

CP-199330: non-toxic alternative to Zafirlukast & Pranlukast, blocks cysteyl LT1 receptors.

MCTR1, a pro-resolving mediator derived from DHA, promotes tissue repair and reduces inflammation by enhancing phagocytosis and decreasing eicosanoids.

MrgprX2 antagonist-6 is a potent antiallergic agent with inhibitory effects on mast cell degranulation.

CI-936 (MRS-3310) is an orally active A2 agonist with a binding affinity of 25 nM. In preclinical studies, it has demonstrated potent and selective effects, indicating potential antipsychotic efficacy. Additionally, CI-936 inhibits exploratory behavior in mice.

Ac-Atovaquone, an ester-acetylated derivative of atovaquone, acts as a potent inhibitor of cytochrome bc1 (cytochrome bc1). This compound shows potential for use in malaria research.

MRS4833 (compound 15) is an orally active, potent, competitive antagonist of P2Y14R, exhibiting IC50 values of 5.92 nM for hP2Y14R and 4.8 nM for mP2Y14R. It reduces airway eosinophilia in protease-mediated asthma models and reverses chronic neuropathic pain in mouse CCI models.

MK-8318 is an effective and selective antagonist of the CRTh2 receptor (Ki: 5.0 nM).

NK-1 Antagonist 1 is a NK-1 receptor antagonist.

LY 245769 is an inhibitor of leukotriene E4 (LTE4).

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

SST1 receptor antagonist-1 (Compound 23) is a selective antagonist of the somatostatin receptor 1 (SST1), showing a pKd of 9.11 for rSST1 and 8.79 for hSST1. This compound is applicable in research related to retinal and endocrine dysfunction, cancer, and neuropsychiatric disorders.

CP-865569 is a CCR1 antagonist useful in the research of inflammatory and autoimmune diseases, including conditions such as rheumatoid arthritis and multiple sclerosis.

MRS4865 (compound 7a) serves as a chimeric antagonist for the P2Y14 receptor and an agonist for UDP-glucose, offering protection against neuropathic pain.

<p>MRS2279 diammonium, a P2Y1 antagonist with K i 2.5 nM, IC 50 51.6 nM, blocks ADP-induced platelet aggregation, pK b 8.05.</p>

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

P2Y2 and P2Y4 receptor agonist

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.

inhibitor of human CCR5 binding to HIV-1 gp120

<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>AM9405: peripheral CB1/5-HT3 agonist, suppresses gut motility, relieves GI disorder symptoms in mice.</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>AMG-369 (AMG 247) is an S1P1/S1P5 dual agonist that delays the development of experimental autoimmune encephalomyelitis in rats.</p>

Teoprolol is a blocker of β-adrenergic receptor.

<p>Cendifensine functions as a monoamine reuptake inhibitor, targeting the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT).</p>

<p>Serotonin hydrogen maleate serves as a monoaminergic neurotransmitter and an endogenous 5-HT receptor agonist within the central nervous system (CNS). It also functions as an inhibitor of catechol O-methyltransferase (COMT), exhibiting a Ki value of 44 μM.</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>SphK1-IN-1: SphK1 ATPase inhibitor, IC50=2.48 μM, potential for cancer research.</p>

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

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

BW A868C is a potent, selective PGD2 antagonist and a BW245C analogue, inert to other prostaglandin receptors.

<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>

GRPR antagonist-2 blocks GRPR, kills some cancer cells, effective on HGC-27 (IC50: 0.77 μM) & Pan02 (IC50: 2.5 μM).

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

AL-8810 is an 11β-fluoro analog of PGF 2α with selective antagonist effects at the PGF 2α receptor (FP receptor) [1].

SSTR5 antagonist 2 hydrochloride: potent, oral SSTR5 blocker with potential in type 2 diabetes research.

<p>Opipramol (Ensidon) is an atypical tricyclic antidepressant (TCA) primarily functioning as a sigma (σ) receptor agonist. It interacts effectively with sigma recognition sites, having a Ki value of 50 nM. Opipramol is applicable in the study of generalized anxiety disorder (GAD).</p>

Merigolix is a potent gonadotrophin releasing hormone (GnRH) antagonist .

N-methyl LTC4 is a stable synthetic analog of LTC4 and a selective CysLT2 agonist, useful in studying leukotriene pharmacology.

Nifeviroc (TD-0232) is an orally active CCR5 antagonist, useful in HIV-1 infection research.

L 668750 is an inhibitor of platelet-activating factor.

<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>

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

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

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.

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> 100 μM; cardiac toxicity IC50= 24.5 μM). It has antidepressant properties and is useful for depression research.

RU 52583 is an alpha 2-adrenergic receptor antagonist.

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

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

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