[CAS NO. 1415390-47-4] (R)-BPO-27
PRODUCTS SPECIFICATIONS [1415390-47-4]
DESCRIPTION [1415390-47-4]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 548.34 |
| Molecular Formula | C26H18BrN3O6 |
| SMILES | O=C(C1=CC=C(O[C@@H](C2=CC=C(Br)O2)C3=C(N(C)C4=O)C(C(N4C)=O)=C(C5=CC=CC=C5)N36)C6=C1)O |
Summary
(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.
IC50 & Target
IC50: 4 nM [1]
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
[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 IC
50
of 600 pM in Single-channel electrophysiology assay
[2]
.
(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
[3]
.
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
[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 IC
50
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.
| Animal Model: | Female CD1 mice (age 8–10 wk) [3] |
| 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. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 14.28 mg/mL ( 26.04 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.8237 mL | 9.1184 mL | 18.2369 mL |
| 5 mM | 0.3647 mL | 1.8237 mL | 3.6474 mL |
| 10 mM | 0.1824 mL | 0.9118 mL | 1.8237 mL |
References
- [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.
- [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.