| Bioactivity | BPO-27 racemate is a potent CFTR inhibitor with an IC50 of 8 nM. | ||||||||||||
| Target | IC50: 8 nM | ||||||||||||
| Invitro | 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]. | ||||||||||||
| In Vivo | Following bolus interperitoneal administration in mice, serum (R)-1 decays with t1/2 ≈ 1.6 h and gives sustained therapeutic concentrations in kidney[1]. | ||||||||||||
| Name | BPO-27 racemate | ||||||||||||
| CAS | 1314873-02-3 | ||||||||||||
| Formula | C26H18BrN3O6 | ||||||||||||
| Molar Mass | 548.34 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
|
||||||||||||
| Reference | [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. |