GPCR/G Protein
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Inhibitors, Agonists, Screening Libraries www.MedChemExpress.com GPCR/G Protein G Protein Coupled Receptors (GPCRs) perceive many extracellular signals and transduce them to heterotrimeric G proteins, which further transduce these signals intracellular to appropriate downstream effectors and thereby play an important role in various signaling pathways. G proteins are specialized proteins with the ability to bind the nucleotides guanosine triphosphate (GTP) and guanosine diphosphate (GDP). In unstimulated cells, the state of G alpha is defined by its interaction with GDP, G beta-gamma, and a GPCR. Upon receptor stimulation by a ligand, G alpha dissociates from the receptor and G beta-gamma, and GTP is exchanged for the bound GDP, which leads to G alpha activation. G alpha then goes on to activate other molecules in the cell. These effects include activating the MAPK and PI3K pathways, as well as inhibition of the Na+/H+ exchanger in the plasma membrane, and the lowering of intracellular Ca2+ levels. Most human GPCRs can be grouped into five main families named; Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2, and Secretin, forming the GRAFS classification system. A series of studies showed that aberrant GPCR Signaling including those for GPCR-PCa, PSGR2, CaSR, GPR30, and GPR39 are associated with tumorigenesis or metastasis, thus interfering with these receptors and their downstream targets might provide an opportunity for the development of new strategies for cancer diagnosis, prevention and treatment. At present, modulators of GPCRs form a key area for the pharmaceutical industry, representing approximately 27% of all FDA-approved drugs. References: [1] Moreira IS. Biochim Biophys Acta. 2014 Jan;1840(1):16-33. [2] Tuteja N. Plant Signal Behav. 2009 Oct;4(10):942-7. [3] Williams C, et al. Methods Mol Biol. 2009;552:39-50. [4] Schiöth HB, et al. Gen Comp Endocrinol. 2005 May 15;142(1-2):94-101. www.MedChemExpress.com 1 Inhibitors, Agonists, Screening Libraries www.MedChemExpress.com Target List in GPCR/G Protein • 5-HT Receptor 4 • GPCR19 137 • Adenosine Receptor 28 • GPR109A 140 • Adenylate Cyclase 35 • GPR119 142 • Adiponectin Receptor 37 • GPR120 144 • Adrenergic Receptor 39 • GPR139 146 • Angiotensin Receptor 59 • GPR40 148 • Bombesin Receptor 67 • GPR55 151 • Bradykinin Receptor 69 • GPR84 153 • Cannabinoid Receptor 72 • Guanylate Cyclase 155 • CaSR 77 • Histamine Receptor 158 • CCR 79 • Imidazoline Receptor 172 • CGRP Receptor 84 • Leukotriene Receptor 174 • Cholecystokinin Receptor 87 • LPL Receptor 178 • CRFR 90 • mAChR 183 • CXCR 93 • MCHR1 (GPR24) 196 • Dopamine Receptor 98 • Melanocortin Receptor 198 • EBI2/GPR183 113 • Melatonin Receptor 201 • Endothelin Receptor 115 • mGluR 203 • GHSR 119 • Motilin Receptor 210 • Glucagon Receptor 122 • Neurokinin Receptor 212 • Glucocorticoid Receptor 127 • Neuropeptide Y Receptor 218 • GNRH Receptor 134 • Neurotensin Receptor 222 2 Tel: 609-228-6898 Fax: 609-228-5909 Email: [email protected] Inhibitors, Agonists, Screening Libraries www.MedChemExpress.com Target List in GPCR/G Protein • Opioid Receptor 224 • Orexin Receptor (OX Receptor) 232 • Oxytocin Receptor 236 • P2Y Receptor 239 • Prostaglandin Receptor 242 • Protease-Activated Receptor (PAR) 252 • Ras 255 • RGS Protein 261 • Sigma Receptor 263 • Somatostatin Receptor 266 • TSH Receptor 269 • Urotensin Receptor 271 • Vasopressin Receptor 273 www.MedChemExpress.com 3 5-HT Receptor Serotonin Receptor;5-hydroxytryptamine Receptor 5-HT receptors (Serotonin receptors) are a group of G protein-coupled receptors (GPCRs) and ligand-gated ion channels (LGICs) found in the central and peripheral nervous systems. Type: 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, 5-HT7. They mediate both excitatory and inhibitory neurotransmission. The serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand. The serotonin receptors modulate the release of many neurotransmitters, as well as many hormones. The serotonin receptors influence various biological and neurological processes such as aggression, anxiety, appetite, cognition, learning, memory, mood, nausea, sleep, andthermoregulation. The serotonin receptors are the target of a variety of pharmaceutical drugs, including many antidepressants, antipsychotics, anorectics,antiemetics, gastroprokinetic agents, antimigraine agents, hallucinogens, and entactogens. 4 Tel: 609-228-6898 Fax: 609-228-5909 Email: [email protected] 5-HT Receptor Inhibitors & Modulators (4E)-SUN9221 (R,R)-Palonosetron Hydrochloride Cat. No.: HY-U00367 Cat. No.: HY-A0021C Bioactivity: (4E)-SUN9221 is a potent antagonist of α1-adrenergic receptor Bioactivity: (R,R)-Palonosetron Hydrochloride is the active enantiomer of and 5-HT2 receptor, with antihypertensive and anti-platelet Palonosetron. aggregation activities. Purity: >98% Purity: 99.61% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg, 10 mg, 20 mg Size: 2 mg, 5 mg, 10 mg (Z)-Thiothixene 5-HT1A modulator 1 Cat. No.: HY-108324 Cat. No.: HY-100290 Bioactivity: (Z)-Thiothixene is an antagonist of serotonergic receptor Bioactivity: 5-HT1A modulator 1 displays very high affinities for the extracted from patent US 20150141345 A1. 5HT1A, adrenergic α1 and dopamine D2 receptor with IC50s of 2 ±0.3 nM, 10 ± 3 nM and 40 ±9 nM, respectively. Purity: 99.14% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 10mM x 1mL in DMSO, Size: 1 mg, 5 mg, 10 mg 5 mg, 10 mg, 25 mg 5-HT2 antagonist 1 5-HT2A antagonist 1 Cat. No.: HY-U00365 Cat. No.: HY-U00286 Bioactivity: 5-HT2 antagonist 1 is a potent antagonist of 5-HT2 receptor, Bioactivity: 5-HT2A antagonist 1 is a 5-HT2A antagonist extracted from with weak α1 adrenoceptor blocking activity. patent US5728835A and JP 1007727. 5-HT2A antagonist 1 may be useful in treatment of gastrointestinal disorders circulatory disorders. Purity: >98% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg, 10 mg, 20 mg Size: 1 mg, 5 mg, 10 mg, 20 mg 5-HT3 antagonist 1 5-HT3 antagonist 2 Cat. No.: HY-U00368 Cat. No.: HY-U00408 Bioactivity: 5-HT3 antagonist 1 is a potent and selective antagonist of Bioactivity: 5-HT3 antagonist 2 is a 5-HT3 receptor antagonist. serotonin 3 (5-HT3) receptor. Purity: >98% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg, 10 mg Size: 1 mg, 5 mg, 10 mg, 20 mg 5-HT3-In-1 5-HT4 antagonist 1 Cat. No.: HY-U00413 Cat. No.: HY-100170 Bioactivity: 5-HT3-In-1 is extracted from patent EP0748807A1, compound Bioactivity: 5-HT4 antagonist 1 is a 5-HT4 receptor antagonist with a example 8. It shows 5-HT3 inhibition activity. pKi of 9.6. Purity: >98% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg, 10 mg, 20 mg Size: 1 mg, 5 mg, 10 mg www.MedChemExpress.com 5 5-HT6/7 antagonist 1 5-HT7 agonist 1 Cat. No.: HY-101622 Cat. No.: HY-109527 Bioactivity: 5-HT6/7 antagonist 1 is a multifunctional ligand that Bioactivity: 5-HT7 agonist 1 is a selective 5-HT7 receptor agonist, with antagonizes 5-HT6/7/2A and D2 receptors, without an IC50 of 222.93 nM, can be used for the 5-HT7 receptor interacting with M1 receptors and hERG channels. related disease, such as CNS disorders. Purity: >98% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 250 mg, 500 mg Size: 250 mg, 500 mg 5HT6-ligand-1 8-OH-DPAT Cat. No.: HY-U00126 (8-Hydroxy-DPAT) Cat. No.: HY-112061 Bioactivity: 5HT6-ligand-1 is a potent 5-HT6 receptor ligand with a Ki of Bioactivity: 8-OH-DPAT is a potent and selective 5-HT agonist, with a pIC of 8.19 for 5-HT1A and a K of 466 nM for 5-HT7; 1.43 nM. 50 i 8-OH-DPAT weakly binds to 5-HT1B (pIC 50, 5.42), 5-HT (pIC 50 <5). Purity: >98% Purity: 98.0% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg, 10 mg, 20 mg Size: 10mM x 1mL in DMSO, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg Abaperidone Adoprazine Cat. No.: HY-101619 (SLV313) Cat. No.: HY-14782 Bioactivity: Abaperidone is a potent antagonist of 5-HT2Areceptor and Bioactivity: Adoprazine, a potential atypical antipsychotic bearing potent D2 receptor antagonist and 5-HT1A receptor agonist properties. dopamine D2 receptor with IC50s of 6.2 and 17 nM. Purity: >98% Purity: 98.13% Clinical Data: No Development Reported Clinical Data: Phase 1 Size: 1 mg, 5 mg, 10 mg, 20 mg Size: 10mM x 1mL in DMSO, 5 mg, 10 mg, 50 mg Agomelatine Agomelatine hydrochloride (S-20098) Cat. No.: HY-17038 (S-20098 hydrochloride) Cat. No.: HY-17038A Bioactivity: Agomelatine is a competitive antagonist of human and porcine Bioactivity: Agomelatine hydrochloride is a antidepressant, which is serotonin (5-HT2C) receptors (pKi = 6.2 and 6.4, respectively) classified as a norepinephrine-dopamine disinhibitor (NDDI) as well as human 5-HT2B receptors (pKi = 6.6). IC50 value: 6.2 due to its antagonism of the 5-HT2C receptor. (pKi, 5-HT2c); 6.6 (pKi, 5-HT2b) Target: 5-HT2C Receptor; 5-HT2B receptor It is classified as a norepinephrine-dopamine… Purity: 99.88% Purity: 99.49% Clinical Data: Launched Clinical Data: Launched Size: 10mM x 1mL in DMSO, Size: 10mM x 1mL in DMSO, 5 mg, 10 mg, 50 mg, 100 mg 5 mg, 10 mg, 50 mg, 100 mg Agomelatine L(+)-Tartaric acid Alniditan (S-20098 L(+)-Tartaric acid) Cat. No.: HY-17038B (Alnitidan) Cat. No.: HY-101698 Bioactivity: Agomelatine (L(+)-Tartaric acid) is a antidepressant, which is Bioactivity: Alniditan is a potent 5-HT1B/1D receptors agonist, with classified as a norepinephrine-dopamine disinhibitor (NDDI) IC of 1.7 and 1.3 nM in HEK293 cells, and pK value of 8.96 due to its antagonism of the 5-HT2C receptor.