GPCR/G-Protein

Bometolol Hydrochloride is a beta-adrenergic blocking compound used for the treatment of cardiovascular disease.

Neladenoson is an effective and selective agonist of the Adenosine A1 Receptor (A1R). EGFR-IN-162 shows potential for research in heart failure.

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.

R-137696 is an orally active 5-HT1A receptor agonist that facilitates the relaxation of the proximal stomach. It is utilized in research related to functional dyspepsia.

Acyline, a GnRH antagonist, suppresses gonadotropins and testosterone in animals and maintains the effect for 2 weeks in men with one dose.

Flucopride (Compound 4a) acts as an acetylcholinesterase inhibitor (AChE) with an IC50 value of 24 nM and serves as a partial agonist for the human 5-HT4 receptor (5-HT4R) with a Ki of 9.6 nM for (h)5-HT4R. It promotes non-amyloidogenic processing of APP in COS-7 cells transiently expressing (h)5-HT4R with an EC50 of 23.0 nM. Flucopride is also likely to exhibit significant gastrointestinal tract (GIT) penetration and blood-brain barrier (BBB) permeability, as determined in PAMPA experiments.

Aeruginosin 98-B, a protease inhibitor, effectively inhibits trypsin, plasmin, and thrombin with IC50 values of 0.6, 7.0, and 10.0 μg/mL, respectively.

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

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.

BMS-986120: Oral, reversible PAR4 antagonist. IC50: 9.5 nM (human), 2.1 nM (monkey). Potent, selective antiplatelet.

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

Thielavin B, from Thielavia terricola, inhibits prostaglandin E2 synthesis and reduces rat oedema.

MRGPRX2 modulator-1 (example 17), a modulator of the mas-related G-protein receptor X2 (MRGPRX2), is employed in studies focused on inflammation, pain, and autoimmune disorders [1].

SJPYT-310 is a selective PXR antagonist, exhibiting no noticeable cytotoxicity.

MK-8825 is a CGRP receptor antagonist.

RS 12254 is a dopamine agonist and antihypertensive agent.

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

A3AR antagonist 5 (Compound 16) acts as a selective antagonist for the human adenosine A3 receptor (human adenosine A3 receptor), with an affinity expressed as a pC value of 4.542 μM.

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.

AGH-107 is a highly selective 5-HT7 receptor agonist that can cross the blood-brain barrier, featuring a Ki value of 6 nM and an EC50 value of 19 nM. Demonstrating high selectivity for central nervous system targets, AGH-107 also exhibits high metabolic stability and low toxicity in HEK-293 and HepG2 cell cultures.

L-657926 is a stereoselective antagonist of the thromboxane A2 (TxA2) receptor, composed of (-)-9-chlorobenzyl-6-fluoro-1,2,3,4-tetrahydrocarbazol-1-yl acetic acid and (+)-9-chlorobenzyl-6-fluoro-1,2,3,4-tetrahydrocarbazol-1-yl acetic acid. The IC50 values for the (-) and (+) configurations against TxA2 are 0.27 nM and 124 nM, respectively.

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

FK-3657 is a non-peptide antagonist of bradykinin (BK)-B2 receptor.

MRT-92 is an antagonist of Smoothened (Smo) with anti-cancer activity, featuring a binding affinity (Ki) of 0.7 nM. It inhibits the Hedgehog signaling pathway by obstructing the overlapping binding sites within the transmembrane domain of the Smoothened receptor and suppresses the proliferation of cerebellar granule cells in rodents (IC50=0.4 nM). MRT-92 is utilized for research into cerebellar gliomas.

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

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

LJ-4517 is an effective A2AAR antagonist (Ki=18.3 nM). LJ-4517 can effectively replace the binding of [3H] ZM241385 at WT A2AAR.

<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>

SB 243213 hydrochloride is an orally active, selective and high-affinity antagonist of 5-hydroxytryptamine (5-HT)2C receptor(pKi of 9.37 and a pKb of 9.8).It

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

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

Compound 29 is a potent, CB2-selective antagonist/reverse agonist. Derivatives 23 & 24 offer antinociception; 24 activates cannabinoid/TRPV1 receptors.

<p>DA-302168S is an orally active, selective GLP-1R agonist with an EC50 value of 1.32 nM. It promotes insulin secretion and has a hypoglycemic effect. Additionally, DA-302168S reduces food intake. It primarily activates GLP-1R in humans and monkeys, with minimal effect on GLP-1R in rats, mice, and dogs. DA-302168S can be used for research in type 2 diabetes and obesity.</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.

BRD50837 is a potent and selective inhibitor of Sonic Hedgehog (Shh).

Dinoxyline is a potent dopamine receptor agonist, with dissociation constants (Ki values) for D1, D2, D3, and D4 receptors being 7 nM, 6 nM, 5 nM, and 43 nM, respectively. It is utilized in neuroscience research.

TGR5 Receptor Agonist 3 is a GPBAR1 agonist with EC50 of 16.4 nM (hTGR5) & 209 nM (mTGR5), ensures gallbladder safety and reduces filling.

L 668750 is an inhibitor of platelet-activating factor.

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

GRK6-IN-5 is an inhibitor of the GRK6 polypeptide, with an IC50 of 4.48 μM. GRK6-IN-5 is utilized in research focused on hematological malignancies, inflammatory diseases, and autoimmune disorders.

Elzasonan hydrochloride is a serotonin 1B and serotonin 1D receptor antagonist. It is utilized in the study of depression.

Monohydroxy Netupitant is a highly selective antagonist of NK1 receptor, and is Netupitant metabolite.

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

Iralukast is a cysteinyl-leukotriene antagonist (CysLT) with a pKi of 7.8 for CysLT1.

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].

DM-4111, one of the primary monohydroxy metabolites of Tolvaptan, is an effective vasopressin V2 receptor (vasopressin V2 receptor) inhibitor. By inhibiting water reabsorption in renal tubules, it facilitates the excretion of electrolyte-free water. DM-4111 holds potential for research in cardiovascular diseases.

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>Mrgx2 antagonist-3 (Compound B-40) is a highly selective antagonist of the MrgX2 receptor, with an IC50 range of 0.042-2.5 nM. It blocks downstream G protein signaling and β-arrestin recruitment, inhibiting Mrgx2 receptor-mediated calcium influx and cell degranulation. Mrgx2 antagonist-3 shows potential for research in inflammation-associated diseases and pruritus, such as chronic urticaria and allergic asthma.</p>

Anti-MRSA agent 19 (Compound 1) is an antibiotic that exhibits activity against Staphylococcus aureus. It is active against 40 clinical isolates from the CDC, representing diverse bacterial species with various resistance factors, including resistance to vancomycin, aminoglycoside/tetracycline, and oxazolidinone (median MIC=4 μg/mL).

NCATS-SM4420 (Compound A35) is an orally effective ligand for the thyroid-stimulating hormone receptor (TSHR) that inhibits the proliferation of MDA-T32 and MDA-T85 cells both in vitro and in vivo, with IC50 values of 0.71 μM and 0.38 μM, respectively. Additionally, it suppresses the metastasis of MDA-T85F1 in mice. NCATS-SM4420 holds potential for research in the field of thyroid cancer.

SSTR4 agonist5 (Compound 5) is an orally active agonist of the somatostatin receptor 4 (SSTR4) with an EC50 of 0.228 nM. It demonstrates good stability in human/rat liver microsomes and can inhibit mechanical hyperalgesia in rat models.

SAR-114137 is a histone sphingomyelin kinase inhibitor used in the study of molluscum arteriosum and peripheral neuropathic pain.

BI-44370, a CGRP (calcitonin gene-related peptide) receptor antagonist, can be used to treat migraines and other chronic pain.

5-HT1A modulator 4 (Compound 1) is a ligand for the 5-HT receptor, with Ki values of 2.18 μM for 5-HT1A and 19.7 μM for 5-HT2A.

<p>BRL-37344 is a selective β3-adrenergic receptor agonist. It significantly reduces the body weight of obese mice.</p>

SB 224289: selective 5-HT1B antagonist, pKi 8.2, 60x selectivity, effective orally.

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.

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

LPA2 antagonist 3 (compound 15) serves as an Lp(a) antagonist. Lp(a) is a pathogenic risk factor for atherosclerotic cardiovascular disease (ASCVD).

BD-1047 is a selective functional antagonist of sigma receptors. It can alleviate climbing behavior induced by Apomorphine and head twitching caused by Phencyclidine.

Delmadinone acetate is an orally active compound used to control estrus and ovulation in both female and male pets. It induces adrenal suppression by inhibiting the pituitary release of ACTH.

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

LRH-1 modulator-1: potent agonist, boosts IL-10, reduces IL-1b/TNFa, anti-inflammatory in gut.

(±)-Penbutolol ((Rac)-Penbutolol) is the racemic form of Penbutolol. It acts as an orally active β-adrenergic receptor antagonist. (±)-Penbutolol mitigates the tachycardia induced by exercise, reduces the increase in peak expiratory flow rate (PEFR) caused by physical activity, and decreases plasma renin activity (PRA) at rest. The peak plasma concentration of this compound is achieved one hour after oral administration, with a half-life of 4.5 hours, and it is metabolized into active metabolites in the body. This compound is utilized in research related to cardiovascular diseases.

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

<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>

AAZ-A 154 hydrobromide is a selective, competitive, non-hallucinogenic 5-HT2AR antagonist. It promotes neuronal growth in rodents and yields enduring beneficial behavioral effects.

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>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>APJ receptor agonist 8 is a small molecule agonist of the APJ receptor, enhancing load-independent cardiac contractility in isolated perfused rat hearts.</p>

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

AAZ-A 154 hydrochloride is a selective, competitive, non-hallucinogenic antagonist of 5-HT2AR. It promotes neuronal growth in rodents and results in enduring beneficial behavioral effects.

A1 adenosine receptor antagonist

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

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.

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].

YNT-3708 is an orexin receptor (OXR) agonist, exhibiting EC50 values of 14.6 nM for OX1R and 277 nM for OX2R.

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

(S)-Praziquantel is the inactive isomer of R-praziquantel.

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

Edonentan (BMS 207940) hydrate effectively blocks the endothelin A (ETA) receptor as a potent and selective antagonist, featuring a K i of 10 pM. It exhibits complete (100%) oral bioavailability in rats [1].

SGLT1/2-IN-8 (compound 8) is a potent and orally active dual inhibitor of SGLT1/2, exhibiting IC50 values of 4 nM and 1 nM, respectively. It shows antihyperglycemic properties, making it suitable for related research.

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.

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

Arpromidine (BU-E-50) acts as an agonist for the histamine H2 receptor and an antagonist for the histamine H1 receptor. It demonstrates positive inotropic effects with a lower risk of inducing arrhythmias. Arpromidine can be utilized in studies related to congestive heart failure.

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

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

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

<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>

KARI 201 hydrochloride is a selective, brain-penetrant, competitive inhibitor of acid sphingomyelinase (ASM) with an IC50 of 338.3 nM. It also acts as an agonist for the growth hormone-releasing peptide receptor (ghrelin receptor). Additionally, KARI 201 hydrochloride can enhance the neuropathological features of Alzheimer's disease.

<p>CB1 antagonist 4 is an inverse agonist of cannabinoid receptor 1 (CB1) with an IC50 of 0.4 nM. It can reduce body weight, improve plasma inflammatory markers, and enhance glucose homeostasis [1].</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).

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.

5-HT6R/MAO-B modulator 1 blocks 5-HT6R and permanently inhibits MAO-B, protects glial cells, and reverses memory loss.

Fasitibant is a potent and selective nonpeptide kinin B2 receptor antagonist.

Dersimelagon phosphate: MC1R agonist, boosts melanin, enhances light tolerance in EPP/XLP without sun.

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

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.