(R)-BPO-27 |
| رقم الكتالوجGC31665 |
(R) -BPO-27 ، R enantiomer لـ BPO-27 ، هو مثبط CFTR فعال عن طريق الفم ومنافس لـ ATP مع IC50 من 4 نانومتر
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1415390-47-4
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
(R)-BPO-27 is a potent CFTR inhibitor with an IC50 of 4 nM.
The benzopyrimido-pyrrolo-oxazinedione BPO-27 is an analogue of PPQ-102, which inhibits CFTR with an IC50 of 8 nM. The R enantiomer of BPO-27 inhibits CFTR chloride conductance with an IC50 of 4 nM, while S enantiomer is inactive. In vitro metabolic stability in hepatic microsomes shows both enantiomers as stable, with less than 5% metabolism in 4 h[1]. (R)-BPO-27 binds near the canonical ATP binding site. Whole-cell patch-clamp studies shows linear CFTR currents with a voltage-independent (R)-BPO-27 block mechanism. At a concentration of (R)-BPO-27 that inhibits CFTR chloride current by 50%, the EC50 for ATP activation of CFTR increases from 0.27 to 1.77 mM[2].
Following bolus interperitoneal administration in mice, serum (R)-1 decays with t1/2 ≈ 1.6 h and gives sustained therapeutic concentrations in kidney[1].
[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.
Cell experiment: | Whole-cell recordings are done on CFTR-expressing CHO-K1 cells. After establishing the whole-cell configuration, BPO-27 is added for 5 minutes, and then CFTR is activated by the addition of forskolin (10 μM) in the continued presence of BPO-27 (0.5 or 1 μM). Whole-cell currents are elicited by applying hyperpolarizing and depolarizing voltage pulses from a holding potential of 0 mV to potentials between +80 and -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]. |
Animal experiment: | Rats: (R)-BPO-27 is formulated at 1 mg/mL in 5% DMSO, 2.5% Tween-80 and 2.5% PEG400 in water. Male mice in a CD1 genetic background are administered 300 μL of the (R)-BPO-27 formulation by intraperitoneal injection. At specified times, blood samples are collected by eye bleed. At 4 h, kidneys are removed following renal arterial perfusion with PBS. Kidneys are weighed, mixed with acetic acid and homogenized for analysis[1]. |
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. | |
| Cas No. | 1415390-47-4 | SDF | |
| Canonical 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 | ||
| Formula | C26H18BrN3O6 | M.Wt | 548.34 |
| الذوبان | DMSO : ≥ 14.28 mg/mL (26.04 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 37 reference(s) in Google Scholar.)
GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *