hGPR91 antagonist 1

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

hGPR91 Antagonist 1 是一种有效的选择性 hGPR91 拮抗剂 (IC50: 7 μM)。GPR91 是一种 7TM G 蛋白偶联受体，最近已用琥珀酸作为其内源配体进行去孤儿化。GPR91 在多种病理生理学中发挥作用，包括肾性高血压、自身免疫性疾病和视网膜血管生成。

hGPR91 antagonist 1 is a potent and selective hGPR91 antagonist (IC50: 7 μM).GPR91, a 7TM G-Protein-Coupled Receptor, has been recently deorphanized with succinic acid as its endogenous ligand.?Current literature indicates that GPR91 plays role in various pathophysiology including renal hypertension, autoimmune disease and retinal angiogenesis.?Starting from a small molecule high-throughput screening hit 1 (hGPR91 IC(50): 0.8 μM)-originally synthesized in Merck for Bradykinin B(1) Receptor (BK(1)R) program, systematic structure-activity relationship study led us to discover potent and selective hGPR91 antagonists e.g. 2c, 4c, and 5 g (IC(50): 7-35 nM;?>1000 fold selective against hGPR99, a closest related GPCR;?>100 fold selective in Drug Matrix screening).?

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HGPR91 antagonist 1 (Compound 4c) leads to 59, 76% inhibition of ΔMAP at 2, 4 hours and has shown rat plasma protein binding 99%. HGPR91 antagonist 1 has engaged the target under the in vivo condition. HGPR91 antagonist 1 hasclearance (CL) of 0.2 nmol/min/mg of RLM. Animal Model:Wistar rats Dosage:100 mg/kg Administration:I.p.; 2 and 4 hours Result:Led to 59 and 76% inhibition of ΔMAP at 2 and 4 hours.

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Cell Cycle/DNA Damage

GPR

HGPR91

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1314796-00-3

529.53

C31H23F4N3O

>98% (HPLC)

In Vitro:?DMSO : ≥ 125 mg/mL (236.06 mM)

O=C(N[C@H](C1=CC=C(C2=CC=C(F)C(C(F)(F)F)=C2)C=C1)C)CC3=CC=C(C4=NC5=NC=CC=C5C=C4)C=C3

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(-20℃)

With Ice Pack

≥ 2 years