(R)-BPO-27, the R enantiomer of BPO-27, is a potent, orally active and ATP-competitive CFTR inhibitor with an IC 50 of 4 nM. In Vitro (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. (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. (R)-BPO-27 is applied directly to the cytoplasmic membrane surface and stabilizes the CFTR channel closed state with an IC 50 of 600 pM in Single-channel electrophysiology assay. (R)-BPO-27 (10 μM, 10 min pretreatment) inhibits Cl - current with apparent IC 50 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 IC 50 of 4 nM for inhibition of forskolin-stimulated CFTR Cl - current in FRT cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only. In Vivo (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 . (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 IC 50 value is 0.1 mg/kg. (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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female CD1 mice (age 8–10 wk)Dosage: 0.05, 0.15, 0.5, 1.5, and 5 mg/kg Administration: Intraperitoneal injection; 5 mg/kg; 30 min before abdominal surgery Result: Exhibited apparent efficacy in mice models of cholera and traveler’s diarrhea. Form:Solid IC50& Target:IC50: 4 nM