hGPR91 antagonist 1

Research use only, not for human use.

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.?

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