(R)-BPO-27 

(R)-BPO-27, the R enantiomer of BPO-27, is a potent, orally active and ATP-competitive CFTR inhibitor with an IC₅₀ of 4 nM.

IC50: 4 nM^[1]

(R)-BPO-27 exhibits a dose-response inhibition and inhibits the CFTR current by 50% at 0.53 nM in HEK-293T cells. (R)-BPO-27 acts from the cytoplasmic side and has low membrane permeability^[1].
(R)-BPO-27 reduces the channel open probability (NPo) from 0.29 to 0.08, modestly reduces in mean channel open time, and strongly increases mean channel closed time in HEK-293T cells expressing human wild-type CFT in a single-channel patch-clamp experiment. Meanwhile, (S)-BPO-27 does not affect any of these parameters^[1].
(R)-BPO-27 is applied directly to the cytoplasmic membrane surface and stabilizes the CFTR channel closed state with an IC₅₀ of 600 pM in Single-channel electrophysiology assay^[2].
(R)-BPO-27 (10 μM, 10 min pretreatment) inhibits Cl^- current with apparent IC₅₀ values of 5 and 10 nM for CPT-cAMP and 8-Br-cGMP, respectively, in CFTR-expressing FRT cells after CFTR stimulation by cAMP agonist. the IC₅₀ of 4 nM for inhibition of forskolin-stimulated CFTR Cl^- current in FRT cells^[3].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

(R)-BPO-27 (interperitoneal administration; 10 mg/kg) decays with t_1/2≈1.6 h and gives sustained therapeutic concentrations in kidney in a PK study^[1].
(R)-BPO-27 (intraperitoneal injection; 5 mg/kg; 30 min before abdominal surgery) prevents fluid accumulation in closed midjejunal loops produced by cholera toxin, giving an intestinal loop weight/length ratio similar to that in PBS-injected loops. This effect is dose-dependently and the IC₅₀ value is 0.1 mg/kg^[3].
(R)-BPO-27 (intraperitoneal injection or oral administration; 5 mg/kg) shows a slow (R)-BPO-27 metabolism and produces sustained serum (R)-BPO-27 levels for at least 4 h. The AUC analysis gave an oral bioavailability of ∼94% for (R)-BPO-27 in mouse pharmacokinetics and toxicity study^[3].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

548.34

C₂₆H₁₈BrN₃O₆

1415390-47-4

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• [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.  [Content Brief]

  [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.  [Content Brief]

  [3]. Onur Cil, et al.Benzopyrimido-pyrrolo-oxazine-dione CFTR inhibitor (R)-BPO-27 for antisecretory therapy of diarrheas caused by bacterial enterotoxins. FASEB J. 2017 Feb;31(2):751-760.  [Content Brief]