GPCR/G-Protein

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.

<p>AMG-369 (AMG 247) is an S1P1/S1P5 dual agonist that delays the development of experimental autoimmune encephalomyelitis in rats.</p>

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.

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.

<p>ATL444 is an adenosine receptor antagonist with affinity (Ki values) for rA1AR, rA2AAR, rA2BAR, and rA3AR of 7.0, 2.5, 61.8, and &gt;1000 nM, respectively.</p>

<p>MDA77 is a CB2 agonist with an EC50 value of 5.82 nM and exhibits no activity towards CB1.</p>

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

UNC10099984A (Compound 6) is a functionally selective ligand for the dopamine D2 receptor, exhibiting a Ki value of 4.6 nM and an EC50 of 6.2 nM for β-arrestin. This compound is useful for research into central nervous system diseases related to the D2 receptor.

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

<p>CHF-6366: M3 antagonist &amp; β2 agonist (pKi 10.4/11.4), mild Ca channel blocker, used in COPD study.</p>

Anthrotainin is a tetracyclic compound that acts as an inhibitor of the binding of P substance (substance P), with an IC50 of 3 μM.

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.

YM-49598 iodide is a tachykinin NK-1 receptor antagonist. It inhibits drug-induced bladder contractions in rats with an IC50 of 11 μg/kg.

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

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.

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

Ici D1542: potent TXS inhibitor & TXA2 receptor antagonist, effective thromboxane blocker in vitro.

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

<p>K-14585 blocks PAR(2), reduces NFkappaB activity, and IL-8 response, but alone can boost IL-8.</p>

LY 292728 is a highly potent antagonist of leukotriene B4 receptor.

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

<p>Nedemelteon is an agonist of the melatonin receptor (melatonin receptor).</p>

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

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

BI-685509: potent, oral sGC activator, boosts cGMP, enhances NO pathways, for CKD/DKD research.

S1PR1 agonist 2 is potent for autoimmune research (from WO2021175225A1).

MK-3207 is a potent, oral CGRP receptor antagonist with high selectivity for human and monkey receptors, inhibiting blood flow in vivo.

<p>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.</p>

A1 adenosine receptor antagonist

<p>Compound 10o, a histamine H3 antagonist-1, functions as both a histamine H3 antagonist and a serotonin reuptake inhibitor, making it useful for research in depression [1].</p>

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

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

<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>

TAK-661 is an inhibitor of eosinophil chemotaxis (eosinophil chemotaxis) that significantly alleviates late-phase bronchoconstriction while inhibiting the proliferation of eosinophils in bronchoalveolar lavage (BAL) and their infiltration into the airway walls.

Tezosentan is an antagonist of the endothelin receptor (pA2s: 9.5, 7.7 for ETA and ETB receptors, respectively).

BAY-899, oral LH-R antagonist, IC50: 185 nM (hLH), 46 nM (rLH), lowers sex hormones in vivo.

<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>

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

CCR1 antagonist13 is a selective small molecule antagonist of CCR1.

PD 135158 is a CCK2 receptor antagonist.

<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>

PF-9404C: S-S diastereoisomer, beta-blocker with vasodilation, boosts cyclic GMP in rat aorta cells from 3 to 53 pmol/mg protein.

Spns2-IN-3 (compound 510) is an SPNS2 inhibitor with an IC50 value of 1.2 μM for hSPNS2. It is applicable in research on autoimmune diseases such as multiple sclerosis (MS) and inflammatory bowel disease (IBD), as well as fibrosis, muscle atrophy, metastasis, acute lung injury, rheumatoid arthritis, colitis, Alzheimer's disease, and other conditions linked to SPNS2 activity.

<p>RTIOXA-43 is an OX2R/OX1R (orexin receptor) dual agonist that increases wakefulnesand is commonly used in studies related to narcolepsy and neural signaling.</p>

<p>TAK-075 is an orally active CaSR antagonist with an IC50 value of 0.94 nM. It transiently stimulates parathyroid hormone (PTH) secretion in rats and effectively prevents significant reduction in PTH secretion due to the accumulation of active metabolites, thereby maintaining a normal secretion pattern. TAK-075 is applicable in research related to metabolic diseases and osteoporosis.</p>

<p>HU 433, a synthetic cannabinoid, acts as a CB2 receptor agonist and is an enantiomer of HU 308. It provides anti-inflammatory and neuroprotective effects by binding to the CB2 receptor, primarily found on immune cells, thereby modulating immune responses and inflammation. Additionally, HU 433 influences microglial signaling pathways, particularly LPS and IFNγ-mediated routes, affecting the phosphorylation of MAPKs, including ERK1/2, JNK, p38, and Akt. This compound is valuable in researching neuroinflammation and retinal diseases.</p>

(2R,3S)-N-(4-(2,6-dimethoxyphenyl)-5-(5-methylpyridin-3-yl)-4H-1,2,4-triazol-3-yl)-3-(5-methylpyrimidin-2-yl)butane-2-sulfonamide is an Apelin receptor agonist

<p>CS-0777 is a potent, selective, and orally active S1P1 agonist (sphingosine 1-phosphate receptor modulator).</p>

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

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.

Tofogliflozin specifically inhibits SGLT2; IC50s are 2.9 nM (human), 14.9 nM (rat), 6.4 nM (mouse).

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

S1P1 agonist 4 exhibits enhanced potency with an EC 50 value of less than 0.05 mg/kg and a predicted human half-life (t1/2) of approximately 5 days, indicating

MRGPRX2 modulator-3 (Compound 4-400) is a quinoline derivative and an MRGPRX2 regulator. It is utilized in the investigation of MRGPRX2-related conditions, including allergies, itching, pain, inflammation, and autoimmune diseases.

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

<p>NBI 35965 hydrochloride is a selective CRF1 (corticotropin-releasing factor receptor 1) antagonist that is both orally active and capable of penetrating the brain. It possesses a K i value of 4 nM and a pK i of 8.5, and does not affect CRF2. This compound effectively diminishes CRF or stress-triggered ACTH (adrenocorticotropic hormone) production in vivo, demonstrating pIC 50 values of 7.1 and 6.9. Additionally, NBI 35965 hydrochloride exhibits anxiolytic properties [1] [2].</p>

L-365260 hemihydrate: selective oral CCK-B/gastrin blocker, Ki=1.9/2.0 nM, competes with guinea pig receptors.

<p>ATX inhibitor 27 (Compound 31) is an ATX inhibitor. It demonstrates IC50 values of 13 nM against human autotaxin (hATX) and 23 nM against lysophosphatidylcholine (LPC). By inhibiting the ATX enzyme, ATX inhibitor 27 reduces LPA levels in the body. This compound is applicable in research related to ATX-LPA-associated conditions such as inflammation, neurodegenerative disorders, and cancer.</p>

<p>SSTR5 antagonist 6, an orally active antagonist specific to the somatostatin receptor subtype 5 (SSTR5), exhibits an IC50 value of 24 nM. This compound is utilized in researching type 2 diabetes [1].</p>

<p>H3R antagonist 5 (Compound 1b) is a selective inverse agonist of the histamine H3 receptor that can penetrate the blood-brain barrier, with an IC50 of 0.54 nM. It is applicable for research related to the central nervous system.</p>

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

5-HT2 receptor antagonist

<p>SJPYT-310 is a selective PXR antagonist, exhibiting no noticeable cytotoxicity.</p>

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

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

BI 639667, an azaindazole-class compound, potently inhibits CCR1 (IC50=1.8 nM in calcium flux assays).

<p>AAZ-A 154 mesylate mesylate is a selective, competitive, and non-hallucinogenic antagonist of 5-HT2AR. It enhances neuronal growth in rodents and produces enduring beneficial behavioral effects.</p>

<p>BI-113823 is an orally active and selective bradykinin B1 receptor antagonist. It alleviates mechanical hyperalgesia induced by complete Freund's adjuvant in rats. BI-113823 is applicable for research on chronic inflammatory pain.</p>

<p>MED 27 is an inhibitor of thromboxane synthase and thromboxane A2 receptors. It effectively inhibits rat platelet aggregation at doses significantly lower than those required for acetylsalicylic acid.</p>

UK 432097 is an adenosine A2A agonist.

<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>

NPRA agonist-11 (Example 161) is an NPRA (NPR1) agonist with AC50 values of 1.681 μM and 0.989 μM for human and monkey, respectively. It is applicable in research on cardiovascular and other diseases.

<p>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.</p>

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

<p>MRS2905 (α,β-Methylene-2-thio-UDP) trisodium is a selective P2Y14R agonist with an EC50 of 0.92 nM. It shows no activity on UDP-activated P2Y6 receptors or other P2Y receptors.</p>

<p>BNS808 is an orally active, selective CB1R antagonist with an IC50 of 0.8 nM, demonstrating significant selectivity for CB2R and minimal brain penetration. It is being studied for the treatment of obesity and related metabolic complications, such as metabolic dysfunction-associated steatotic liver disease (MASLD). BNS808 reduces drug exposure to the central nervous system, enhancing safety, and minimizes drug interactions through high plasma protein binding.</p>

Cloprostenol is a synthetic prostaglandin and PGF2α analogue used in animals to terminate pregnancy and induce corpus luteum dissolution.

Becondogrel (2-Oxoclopidogrel) is a metabolite of Clopidogrel. It irreversibly inhibits the P2Y12 receptor, thereby preventing platelet aggregation and thrombosis.

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.

SR 140333 is a NK1 receptor antagonist.

MK-8825 is a CGRP receptor antagonist.

Danavorexton is an orexin receptor agonist.

LY3154207: selective, potent oral human dopamine D1 receptor PAM, low agonist activity, EC50=3 nM.

<p>(1R,2S,3R)-Aprepitant (Compound ent-4) is a competitive antagonist of the human neurokinin-1 (NK-1) receptor. It holds potential for research in the treatment of nausea and vomiting related to cancer or postoperative conditions.</p>

<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>

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

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

<p>PD-136,450: partial stomach secretory agonist, full pancreas agonist in rats; potential acid-reducing drug, adjuvant for gastrin-sensitive tumors.</p>

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

<p>GHSR-1a agonist-1 (Compound 4b) is an orally active agonist of the human growth hormone secretagogue receptor 1a (GHSR-1a) with an EC50 of 0.49 nM. It effectively stimulates the release of endogenous growth hormone by activating GHSR-1a. Doses as low as 0.1 mg/kg (administered orally) can increase body weight and length in 4-week-old rats. GHSR-1a agonist-1 is applicable in research on pediatric growth and developmental delays.</p>

<p>MRS7799 is a selective A3 Adenosine Receptor antagonist with Kd values of 0.55 nM for humans, 3.74 nM for mice, and 2.80 nM for rats. MRS7799 can be utilized in research related to neurodegenerative diseases, cancer, cardiac and cerebral ischemia, and autoimmune inflammatory diseases.</p>

BMS-986104 is a potent and selective S1P1 receptor modulator.

<p>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.</p>

VGD071, a compound that targets sortilin, presents a promising avenue for forthcoming research utilizing mouse models of breast cancer.

SCH-900822 is a potent and selective glucagon receptor antagonist.

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.

GLP-1R agonist 33 (Compound 224) is a GLP-1 receptor agonist with potential applications in research related to diabetes, obesity, and non-alcoholic fatty liver disease (NAFLD).

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