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BMS-927711
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
BMS-927711图片
CAS NO:1289023-67-1
规格:98%
分子量:534.56
包装与价格:
包装价格(元)
10mg电议
50mg电议
100mg电议

产品介绍
CGRP receptor antagonist
CAS:1289023-67-1
分子式:C28H28F2N6O3
分子量:534.56
纯度:98%
存储:Store at -20°C

Background:

BMS-927711 is an orally potent CGRP receptor antagonist with IC50 of 0.14 nM. [1]
Calcitonin gene-related peptide CGRP is a 37 amino acid peptide widely distributed in the nervous system, which is a highly potent vasodilator that has been directly implicated in the pathology of migraine. Studies have revealed that plasma concentrations of CGRP are elevated during migraine attacks, and these levels could be normalized by sumatriptan in connection with the relief of headache. CGRP receptors are G-coupled cell surface receptors composed of the calcitonin receptor-like receptor (CLR), receptor activity modifying protein 1 (RAMP1), and the receptor component protein (RCP). BMS-927711 is an antagonist of CGRP receptor and could alleviate migraine. [1, 2]
Binding affinities for the human CGRP receptor were determined by inhibition of 125I-CGRP binding to SK-N-MC cell membranes, which endogenously express receptor. BMS-927711 was shown to be a full, competitive antagonist with IC 50 = 0.14±0.01 nM. Moreover, it showed excellent permeability in tests of PAMPA. Functional receptor antagonism for BMS-927711 was determined by measuring inhibition of CGRP-stimulated cAMP production in SK-N-MC cells. [1]
In a large Phase 2b study testing BMS-927711 for the acute treatment of migraine, an adaptive design to test six doses of BMS-927711 (10, 25, 75, 150, 300 and 600 mg) against placebo was adopted while Sumatriptan 100 mg was used as an active comparator. BMS-927711 was proved to be effective at multiple doses. For the primary endpoint, namely the proportion pain-free at 2 hours post dose, doses of 75 mg, 150 mg and 300 mg (as well as sumatriptan) were superior to placebo. However, 600mg showed no additional benefits over lower doses. Besides, efficacy was numerically inferior to sumatriptan for this endpoint for all doses. [2]
参考文献:
[1]. Luo G, Chen L, Conway C M, et al. Discovery of (5 S, 6 S, 9 R)-5-Amino-6-(2, 3-difluorophenyl)-6, 7, 8, 9-tetrahydro-5 H-cyclohepta [b] pyridin-9-yl 4-(2-oxo-2, 3-dihydro-1 H-imidazo [4, 5-b] pyridin-1-yl) piperidine-1-carboxylate (BMS-927711): An Oral Calcitonin Gene-Related Peptide (CGRP) Antagonist in Clinical Trials for Treating Migraine[J]. Journal of medicinal chemistry, 2012, 55(23): 10644-10651.
[2]. Bigal M E. BMS-927711 for the acute treatment of migraine[J]. Cephalalgia, 2013: 0333102413500728.