(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.

Product information

CAS Number: 1415390-47-4

Molecular Weight: 548.34

Formula: C26H18BrN3O6

Chemical Name: (9R)-9-(5-bromofuran-2-yl)-12,14-dimethyl-13,15-dioxo-17-phenyl-8-oxa-1,12,14-triazatetracyclo[8.7.0.0²,⁷.0¹¹,¹⁶]heptadeca-2,4,6,10,16-pentaene-4-carboxylic acid

Smiles: CN1C(=O)C2C(=C3[C@@H](OC4=CC=C(C=C4N3C=2C2C=CC=CC=2)C(O)=O)C2=CC=C(Br)O2)N(C)C1=O

InChiKey: GNHIGSRGYXEQEP-QHCPKHFHSA-N

InChi: InChI=1S/C26H18BrN3O6/c1-28-21-19(24(31)29(2)26(28)34)20(13-6-4-3-5-7-13)30-15-12-14(25(32)33)8-9-16(15)36-23(22(21)30)17-10-11-18(27)35-17/h3-12,23H,1-2H3,(H,32,33)/t23-/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : ≥ 14.28 mg/mL (26.04 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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 IC50 of 600 pM in Single-channel electrophysiology assay. (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.

In Vivo:

(R)-BPO-27 (interperitoneal administration; 10 mg/kg) decays with t1/2≈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 IC50 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.

Products are for research use only. Not for human use.