BPO-27racemate是有效的CFTR抑制剂，IC50值为8nM。
CAS：1314873-02-3
分子式：C26H18BrN3O6
分子量：548.34
纯度：98%
存储：Store at -20°C

Background:

BPO-27 racemate is a potent CFTR inhibitor with an IC50 of 8 nM.

The benzopyrimido-pyrrolo-oxazinedione BPO-27 is an analogue of PPQ-102, which inhibits CFTR with an IC50 of 8 nM. The R enantiomer of BPO-27 inhibits CFTR chloride conductance with an IC50 of 4 nM, while S enantiomer is inactive. In vitro metabolic stability in hepatic microsomes shows both enantiomers as stable, with less than 5% metabolism in 4 h[1]. (R)-BPO-27 binds near the canonical ATP binding site. Whole-cell patch-clamp studies shows linear CFTR currents with a voltage-independent (R)-BPO-27 block mechanism. At a concentration of (R)-BPO-27 that inhibits CFTR chloride current by 50%, the EC50 for ATP activation of CFTR increases from 0.27 to 1.77 mM[2].

Following bolus interperitoneal administration in mice, serum (R)-1 decays with t1/2 ≈ 1.6 h and gives sustained therapeutic concentrations in kidney[1].

[1]. Snyder DS, et al. Absolute Configuration And Biological Properties of Enantiomers of CFTR Inhibitor BPO-27. ACS Med Chem Lett. 2013 May 9;4(5):456-459. [2]. Kim Y, et al. Benzopyrimido-pyrrolo-oxazine-dione (R)-BPO-27 Inhibits CFTR Chloride Channel Gating by Competition with ATP. Mol Pharmacol. 2015 Oct;88(4):689-96.