Proteina G/GPCR

P2Y2 and P2Y4 receptor agonist

SB-423557 is an orally active antagonist of calcium-sensing receptor (CaR) with IC50 of 520 nM

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.

TAK-024 is an inhibitor of platelet(IC50s of 31, 79 and 51 nM in human, monkey and guinea pig, respectively).

BER-5 is a potent MrgX2 antagonist, demonstrating broad-spectrum antagonistic activity against various MrgX2 agonists. It can inhibit Substance P(SP)-induced degranulation in LAD2 cells and alleviate SP-induced allergic reactions in mice. BER-5 is useful for researching mechanisms related to allergic reactions.

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.

CM699 is an effective dual inhibitor of the dopamine transporter (DAT) and Sigma receptor (σR), with IC50 values of 311 nM and 14.1 nM, respectively.

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.

NK3 receptor antagonist

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

25C-NBF hydrochloride is an agonist of 5-HT receptors, specifically activating 5-HT2A and 5-HT2C receptors, with an EC50 of approximately 0.3 μM.

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.

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

SphK2-IN-2 (21g) is a potent and selective inhibitor of SphK2 (IC50: 0.23 μM).

MDMB-FUBICA is a potent agonist of the cannabinoid receptors and exhibits psychoactive properties. It can be utilized in e-cigarettes.

Lisuride: an oral D2 dopamine agonist, ergot derivative, used in Parkinson's, migraine, and high prolactin research.

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

PD 140376: Selective CCK-B/gastrin receptor antagonist radioligand for guinea pig stomach & brain.

INCB-9471 HCl: a potent CCR5 antagonist, blocks monocyte migration & HIV-1.

SB 258741 hydrochloride is a potent antagonist of the 5-HT 7 receptor, designed specifically for studying schizophrenia [1].

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

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

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

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

Dopamine D4 receptor ligand 3 (Compound 16) functions as a dopamine D4 receptor (D4R) antagonist with a pKi of 8.86. In HEK-293T cells, it shows pIC50 values of 5.78, 5.55, and 6.17 for Go, Gi, and βArr2 sensors, respectively. This compound inhibits the activity of human glioma cell lines U87 MG, T98G, and U251 MG, and it induces ROS production and mitochondrial dysfunction in these glioma cells.

AH22921 is an EP4 prostaglandin receptor antagonist with the ability to antagonize the activation of adenylyl cyclase by prostaglandins in CHO cells. It induces a rightward shift in the PGE? concentration-response curve in these cells, functioning as a non-competitive antagonist. AH22921 is selective for the EP4 receptor, inhibiting its activity in CHO cells without affecting the PGE? concentration-response curve in NPE cells that contain the EP2 receptor.

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

Zafirlukast metabolite M1 (compound 15) is an inhibitor used in the treatment of asthma and other allergic pulmonary conditions, effectively antagonizing leukotriene activity.

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

<p>PF-06372222: a small-molecule that modulates GCGR and antagonizes GLP-1R, affecting insulin and glucagon.</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.

5-HT2 receptor antagonist

Oral antiplatelet agent 1 is a potent antiplatelet agent with an IC50 of 2.94 μM in vitro.

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.

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

CCK2 (CCK-B) 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.

Compound (−)-19, also known as (-)-5-HT2C agonist-3, is a selective 5-HT2C agonist exhibiting a preference for Gq signaling. It demonstrates efficiency with EC50 values for 5-HT2 receptor subtypes as follows: 5-HT2C at 103 nM, 5-HT2B at 570 nM, and 5-HT2A at 72 nM. This compound is utilized in research on antipsychotics.

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

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.

SGLT inhibitor-1 is a potentsodium glucose co-transporter proteins (SGLTs) dual inhibitor(hSGLT1 and hSGLT2 with IC50s of 43 nM and 9 nM, respectively).

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.

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

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

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.

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

25B-NBOH hydrochloride is a phenethylamine that exhibits high affinity for serotonin (5-HT) receptors 5-HT2A and 5-HT2C, with pKi values of 8.3 and 9.4, respectively.

Atumelnant (CRN04894) is an MC2R antagonist used in the study of congenital adrenocortical hyperplasia (CAH) and Cushing's disease (CD).

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

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.

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

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.

D3/5-HT receptor modulator-1 (compound 5i) is a selective antagonist of the dopamine D3 and 5-HT2A receptors, and a partial agonist at the 5-HT1A receptor. It exhibits Ki values of 4.5 nM, 11.9 nM, and 15.3 nM for the dopamine D3, 5-HT2A, and 5-HT1A receptors respectively. The compound shows lower affinity for the dopamine D2 receptor, 5-HT2C receptor, and hERG channel. D3/5-HT receptor modulator-1 possesses atypical antipsychotic properties.

Zaladenant is an adenosine receptor antagonist with antitumor properties.

Potent, oral SSTR5 antagonist 2 TFA may treat type 2 diabetes.

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.

GRK6-IN-4 is an inhibitor of G protein-coupled receptor kinase 6 (GRK6) with an IC50 value of 1.56 μM. GRK6-IN-4 is applicable for research related to hematological malignancies, inflammatory diseases, and autoimmune disorders.

Potent, selective D4R antagonist; IC50 = 6.87 µM; potential in Parkinson’s disease research.

CI-624 reduces the secretion and output of hydrogen ions, sodium ions, potassium ions, and pepsin. This compound may be utilized in research focusing on cancer and autoimmune diseases.

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.

GnRH antagonist 2 is a GnRH receptor antagonist, useful for studying endocrine diseases.

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

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].

CCR3 antagonist2 (example 66) is a CCR3 antagonist useful for researching inflammatory or allergic diseases, particularly those affecting the respiratory tract, such as inflammatory or obstructive airway conditions.

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.

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

Danavorexton is an orexin receptor agonist.

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.

LPA2 antagonist 5 (EX1) functions as an antagonist of LPA2, with an IC50 value of 4.05 nM.

Aplaviroc, a potent CCR5 inhibitor, binds selectively, blocking HIV entry and specific monoclonal antibody attachment in vitro.

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

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

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.

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

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) .

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

SR2640 is a potent and highly selective LTD4/LTE4 antagonist, specifically inhibiting LTD4-induced contractions in guinea pig ileum and tracheal smooth muscle in a concentration-dependent manner, without affecting histamine-induced contractions. It blocks the binding of 0.4 nM [3H]LTD4 to guinea pig lung membrane receptors with an IC50 of 23 nM. SR2640 also causes a parallel rightward shift in the dose-response curve for LTD4-induced bronchoconstriction in guinea pigs when administered intravenously, with the degree of shift correlating positively with its dosage. SR2640 is applicable for asthma research.

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

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.

ZD6021 is an antagonist of neurokinin 1 receptor.

GLP-1 Receptor Agonist 10 (Compound 42), an agonist of the GLP receptor, reduces glucose excursions and inhibits food intake in mice. It is useful for research into type 2 diabetes (T2DM) and obesity [1].

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.

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

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

L 156903 is a bioactive chemical. It also inhibits the binding of neurotensin to brain tissue.

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.

JKC 302 is an ET-A receptor antagonist that partially inhibits the contraction of tracheal rings in asthmatic rats induced by ET-1.

5-HT2/5-HT7 receptor antagonist

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>EP4 receptor agonist 3 is an activator of the EP4 receptor and is useful for research in the DSS-induced colitis mouse model.</p>

Gemilukast (ONO-6950) is a cysteinyl leukotriene 1 and 2 receptor inhibitor that inhibits bronchoconstriction and is used in the treatment of asthma.

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

(Rac)-Nebivolol, a racemic β1-adrenergic blocker (IC50=0.8 nM), has vasodilatory properties and mitigates ethanol-induced cardiac harm.

hA3AR agonist 1 is a potent human A 3 adenosine receptor (hA 3 AR) agonist (Ki = 2.40 nM) .

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.

THRX-194556 is an agonist of the 5-HT4 receptor. It is applicable in the study of gastrointestinal functional disorders and Alzheimer's disease.

<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>

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