BPO-27-racemate - CFTR 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBPO-27 racemateCat. No.: HY-19778ACAS No.: 1314873-02-3分式: CHBrNO分量: 548.34作靶點(diǎn): CFTR作通路: Membrane Transporter/Ion Channel儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 6 mg/mL (10.94 mM; N

2、eed ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 1.8237 mL 9.1184 mL 18.2369 mL5 mM 0.3647 mL 1.8237 mL 3.6474 mL10 mM 0.1824 mL 0.9118 mL 1.8237 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 BPO-27 racemate是有效的CFTR抑制劑，IC50值為8 nM。IC50 & Target IC50

3、: 8 nM 1體外研究The benzopyrimido-pyrrolo-oxazinedione BPO-27 is an analogue of PPQ-102, which inhibits CFTR with anIC50 of 8 nM. The R enantiomer of BPO-27 inhibits CFTR chloride conductance with an IC50 of 4 nM, whileS enantiomer is inactive. In vitro metabolic stability in hepatic microsomes shows bo

4、th enantiomers as stable,1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEwith less than 5% metabolism in 4 h 1. (R)-BPO-27 binds near the canonical ATP binding site. Whole-cellpatch-clamp studies shows linear CFTR currents with a voltage-independent (R)-BPO-27 block mechanism.At a concentration of

5、(R)-BPO-27 that inhibits CFTR chloride current by 50%, the EC50 for ATP activation ofCFTR increases from 0.27 to 1.77 mM 2.體內(nèi)研究 Following bolus interperitoneal administration in mice, serum (R)-1 decays with t1/2 1.6 h and givessustained therapeutic concentrations in kidney 1.PROTOCOLCell Assay 2 Wh

6、ole-cell recordings are done on CFTR-expressing CHO-K1 cells. After establishing the whole-cellconfiguration, BPO-27 is added for 5 minutes, and then CFTR is activated by the addition of forskolin (10 M)in the continued presence of BPO-27 (0.5 or 1 M). Whole-cell currents are elicited by applyinghyp

7、erpolarizing and depolarizing voltage pulses from a holding potential of 0 mV to potentials between +80and 80 mV in steps of 20 mV. Recordings are made at room temperature using an Axopatch-200B.Currents are digitized with a Digidata 1440A converter and filtered at 5 kHz 2.MCE has not independently

8、confirmed the accuracy of these methods. They are for reference only.Animal Mice: (R)-BPO-27 is formulated at 1 mg/mL in 5% DMSO, 2.5% Tween-80 and 2.5% PEG400 in water. MaleAdministration 1 mice in a CD1 genetic background are administered 300 L of the (R)-BPO-27 formulation by intraperitonealinjec

9、tion. At specified times, blood samples are collected by eye bleed. At 4 h, kidneys are removed followingrenal arterial perfusion with PBS. Kidneys are weighed, mixed with acetic acid and homogenized for analysis1.MCE has not independently confirmed the accuracy of these methods. They are for refere

10、nce only.REFERENCES1. 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. MolPharmacol. 2015 Oct;88(4):689-96.McePdfHeightCaution: Product has not been fully va