GPCR/G-Protein

Rodatristat ethyl is an oral TPH1 inhibitor reducing 5-HT levels & lowering PAH at low doses.

LX2761 is a stable inhibitor for SGLT1/2 with IC50s of 2.2/2.7 nM; it targets SGLT1 in the GI tract.

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

BMS-986104 is an effective selective modulator of the S1P1 receptor. It demonstrates efficacy in the mouse EAE model, comparable to that of FTY720. Furthermore, BMS-986104 shows promising remyelination properties in three-dimensional brain cell cultures subjected to lysophosphatidylcholine (LPC)-induced demyelination.

Nocloprost (SH 475) is a prostaglandin E2 (PGE2) analog, an EP1 and EP3 receptor agonist with local gastric protection and ulcer healing effects.

RBM10-8 irreversibly inhibits human sphingosine-1- phosphate lyase (hS1PL) while behaving also as an enzyme substrate.

Fosrolapitant is an antagonist of the neurokinin 1 (NK1) receptor.

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

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

LK-732 is a thrombin inhibitor with antithrombotic activity. It exhibits dose-dependent inhibition in models of hypercoagulability, with an IC50 value of 1.3 mg/kg. LK-732 is used in cardiovascular and cerebrovascular research.

Sitamaquine hydrochloride (WR 6026) is an orally active 8-aminoquinoline analog with antileishmanial activity. This compound inhibits mitochondrial complex II (succinate dehydrogenase) and is characterized by its lipophilic weak base properties. It rapidly accumulates in the acidic compartments of Leishmania parasites, predominantly localizing within the acidocalcisomes.

DCB-3503, a tylophorine analog, may treat cancer and suppress immunity by blocking protein synthesis and modulating HSC70's ATPase activity.

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

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

PD-147693 (compound II) is an active metabolite of the presynaptic dopamine autoreceptor agonist CI-1007, and it exhibits antipsychotic activity similar to CI-1007.

PF-4693627 is an effective and selective microsomal prostaglandin E synthase-1 inhibitor (IC50=3 nM).

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

OP-2507, a prostacyclin agonist, is used potentially for the treatment of hepatic insufficiency and hypertension.

Iloprost, a potent prostacyclin analog, binds to human IP & EP1 receptors with high affinity; inhibits platelet aggregation effectively.

VU0514009 is a competitive antagonist of chemokine-like receptor 1 (CMKLR1) with an EC50 of 2 nM. It effectively inhibits chemerin-9-induced arrestin recruitment and receptor internalization, significantly reducing Ca2+ flux responses in HEK293 cells. This compound shows potential for research in inflammatory diseases and metabolic syndrome.

Orvepitant is a potent and selective NK1 antagonist, which may be potentially useful for patients with major depressive disorder (MDD), anxiety and insomnia.

Tixanox sodium effectively blocks histamine release in the lungs triggered by anti-IgE. It has also been demonstrated that when administered orally, Tixanox sodium can successfully counteract exercise-induced asthma.

RWJ-68022 (Example 9) is a cyclopentene derivative that serves as a motilin receptor antagonist. It competes with motilin and erythromycin at motilin receptor sites and is applicable in research on gastrointestinal disorders.

CTW0404 is an effective positive allosteric modulator (PAM) of the 5-HT receptor, with promising implications for research into neuropsychiatric disorders.

SSR 146977 hydrochloride is a potent, selective antagonist of the tachykinin NK 3 receptor, and it can be utilized in research on psychiatric disorders and airway inflammation [1].

Osanetant HCl is the (R)-enantiomer; neurokinin-3 receptor antagonist

DNA crosslinker 6 (compound 1) is an anti-mitotic agent known for its strong binding affinity to AT-DNA and inhibition of AT-hook 1 binding to DNA (IC50=0.03 µM). Additionally, it exhibits anti-protozoal activity, effectively inhibiting T. brucei with an EC50 of 0.83 µM.

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.

Serlopitant is a selective antagonist of Neurokinin-1 (NK-1) receptor.

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

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.

LK-11, an alkaloid derivative, inhibits the passive uptake of norepinephrine (NA) by synaptic vesicles in the thalamus, similarly to cocaine.

Beloxepin is an oral dual selective inhibitor of serotonin and norepinephrine uptake.

Quinagolide Free Base is a non-ergot dopamine D(2)-agonist.

AChE-IN-5: oral, crosses blood-brain barrier, targets AChE/5-HT1A/SERT, potent with 2.29 nM IC50.

MSX-3 is an antagonist of the A2A adenosine receptor and a prodrug of MSX-2.

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

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.

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).

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.

FDU-PB-22, a novel synthetic cannabinoid, undergoes rapid metabolism in human liver microsomes (HLM) with a half-life of 12.4 minutes.

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) .

O-1269 acts as a partial agonist for the cannabinoid receptor 1 (CB1R), with a binding affinity (Ki) of 32 nM. Additionally, it exhibits analgesic properties.

AB-FUBINACA 3-fluorobenzyl isomer is a synthetic cannabinoid and an indazole derivative, exhibiting high affinity for central CB1 receptors (Ki= 0.9 nM) and possessing anticonvulsant activity.

Butopamine hydrochloride is an orally active inotropic compound that is more effective at increasing heart rate compared to Dobutamine.

Tipindole is a serotonin antagonist utilized in research related to depression.

Sulfinalol hydrochloride is an orally active β-adrenoceptor (β-adrenoceptor) antagonist that exhibits direct vasodilatory activity. It is also classified as an antihypertensive agent.

<p>Org 274179-0 is an effective allosteric antagonist of the thyroid-stimulating hormone (TSH) receptor, with an IC50 in the nanomolar range. It fully inhibits TSH (and TSI)-mediated activation of the TSH receptor with minimal impact on the efficacy of TSH. This compound can be utilized in studies of Graves' disease (GD).</p>

BAY 38-7271: potent neuroprotective, selective CB1/CB2 agonist, Ki of 1.85 nM (CB1) & 5.96 nM (CB2).

CRHR1 antagonist 1 (compound 10a) is a non-peptide antagonist of corticotropin-releasing hormone receptor 1 (CRHR1). It serves as a useful tool in the study of psychiatric disorders.

(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.

CGRP antagonist 7 is a potent calcitonin gene-related peptide receptor (CGRP) antagonist with a Ki value of 0.029 nM. It effectively inhibits CGRP receptor-mediated cyclic adenosine monophosphate (cAMP) production, with an IC50 value of 1.5 nM. This compound is useful in migraine research.

GPR27 agonist-1 (compound I) is a selective agonist for GPR27 with a pEC50 value of 6.34.

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).

CBR Agonist-2: CB1 receptor agonist, EC50 - 960 nM, Ki - 970 nM, useful for hCB1R-related disease research.

SS-RJW100 is an enantiomer of RJW100 targeting LRH-1, SF-1, enhances Tif2 interaction, and disrupts LRH-1 networks with lowered stability.

Compound 12a (D1R antagonist 1) is a D1R antagonist that participates in both G-protein-coupled and β-arrestin-mediated signaling pathways [1].

UK 432097 is an adenosine A2A agonist.

Dopamine D3 receptor antagonist-1 is a dopamine D3 receptor selective or multi-targeting ligand with a Ki value of 1.58 nM that has demonstrated therapeutic

SSTR4 agonist 4, potent in pain research, shows promise in rodent pain models, with potential for Alzheimer's due to hippocampus activity.

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.

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.

U91356 is an agonist of the dopamine receptors.

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

RG-15 is an orally active dopamine receptor antagonist with high affinity for the human D2 receptor (pKi of 8.23) and human D3 receptor (pKi of 10.49). It inhibits dopamine-stimulated [35S]GTPγS binding with IC50 values of 21.2 nM in rat striatal membranes, 36.7 nM in mouse A9 cells expressing human D2L receptors, and 7.2 nM in CHO cells expressing human D3 receptors. RG-15 enhances dopamine turnover and synthesis in the striatum and olfactory bulb of mice, exhibiting antipsychotic activity.

BIIE-0246: A potent, non-peptide Y2 receptor antagonist; >650-fold more selective than Y1, Y4, Y5.

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

9-Methyl-β-carboline is a cognitive enhancer with neuroprotective, neurorestorative, and anti-inflammatory properties. Its behavioral effects may be linked to hippocampal dopamine levels and the stimulation of dendritic and synaptic proliferation.

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

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).

ONO-8809: Thromboxane A2 antagonist, reduces airway hyperresponse, macrophage accumulation, and MMP-9 in SHRSP brains.

SGL5213 is a potent oral SGLT1 inhibitor (IC50: 29 nM) with potential for treating type 2 diabetes.

Potent 5-HT6/5-HT2A receptors dual antagonist with K i of 11 nM & 39 nM.

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

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.

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.

Tebideutorexant, an orexin-1 receptor antagonist, shows anti-panic effects in rodents and humans, providing a tool for stress response and psychiatric research.

PGD2 is involved in allergy, asthma, sleep, temperature regulation, inhibits clotting, and relaxes blood vessels; PGDM, its metabolite, is a biomarker.

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.

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

RXFP1 receptor agonist-10 (Compound 188) is an RXFP1 receptor agonist with an EC50 of 0.5 nM. It is useful for research into heart failure.

(S)-Butaprost (free acid) is a potent and highly selective EP2 receptor agonist[1].

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

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].

LB-102 is an orally active inhibitor of dopamine D2, D3, and serotonin 5-HT7 receptors, utilized in the study of schizophrenia and other psychiatric disorders.

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

CVN766 is an orally active orexin 1 receptor antagonist with blood-brain permeability, demonstrating IC50 values of 8 nM for OX1R and >10 μM for OX2R. CVN766 can be used to study schizophrenia [1].

<p>Befiradol HCl (NLX-112) is a selective 5-HT1A receptor agonist with anxiolytic effects and prevents ATXN3 aggregation.</p>

Avitriptan is a 5-HT1B/1D receptor agonist with pKi values of 7.44 for 5-HT1Brat, 7.68 for 5-HT1Bhuman, and 8.36 for 5-HT1Dhuman. It can induce contraction in isolated coronary arteries and is used for the treatment of migraines.

LAB687 (Compound 2a) is an inhibitor of microsomal triglyceride transfer protein (MTP) with an IC50 of 0.9 nM for inhibiting the secretion of apolipoprotein B (apoB) in HepG2 cells. Additionally, LAB687 acts as a Smoothened (Smo) antagonist, exhibiting IC50 values of 2.48 μM and 3.42 μM for mouse and human Smo receptors, respectively. This compound is effective in reducing triglyceride and low-density lipoprotein cholesterol (LDL-C) levels and in inhibiting the Hedgehog signaling pathway.

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

5-HT2A receptor agonist-7 (517) functions as a modulator of the 5-HT2A receptor, with an EC50 value of less than 100 nM.

Cicaprost (ZK 96480) is an IP agonist with artery relaxing effects; EC50 is 5.8 nM.

Taranabant: potent CB1 receptor inverse agonist; inhibits agonists with 0.13 nM Ki in vitro.

Vibegron (MK-4618) is an effective and selective Beta 3 adrenergic receptor agonist, used to treat overactive bladder (OAB).

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.

Iloprost, a potent prostacyclin analog, binds IP & EP1 receptors (Ki 11 nM), contains 16(S/R) isomers, and inhibits platelets (IC50 65 nM).

Sp-UTP-α-S serves as an activator of P2Y2 and P2Y4 receptors and is applicable in cancer research.