(R)-BPO-27
目录号 : GC31665
(R)-BPO-27是有效的CFTR抑制剂，IC50值为4nM。
Cas No.:1415390-47-4
Sample solution is provided at 25 µL, 10mM.
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(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 | ||
| 分子式 | C26H18BrN3O6 | 分子量 | 548.34 |
| 溶解度 | DMSO : ≥ 14.28 mg/mL (26.04 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet