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BDK Inhibitor II, (S)-CPP-Calbiochem

BCKD Kinase Inhibitor II, Branched-Chain α-Ketoacid Dehydrogenase Kinase Inhibitor II, (S)-α-Chloro-phenylpropionic acid

品牌
Sigma-Aldrich
货号
5.05602
规格纯度
A cell-permeable inhibitor of mitochondrial branched-chain α-ketoacid dehydrogenase complex (BCKDC) regulatory kinase BDK (IC50 = 6.3 μM).
参考价格
2289.97 *本价格含增值税费
促销
数量
-+
产品介绍:

产品说明

一般描述

A cell-permeable chlorophenylpropionate compound that is superior to its structural analog 4PB (Cat. No. 567616) as an inhibitor against mitochondrial BCKDC (branched-chain α-ketoacid dehydrogenase complex) regulatory kinase BDK (BCKD kinase; IC50 = 6.3 vs. 53.1 µM) due to much optimized affinity toward the BDK N-terminal allosteric site (Kd = 2.4 vs. 5.7 µM) via carboxylate oxygens-mediated hydrogen bonds, as well as hydrophobic interactions mediated by the α-chlorine and the phenyl ring, effectively blocking BDK substrate access by preventing BDK interaction with the homo-24-meric dihydrolipoyltransferase BCKDC E2 component, while exhibiting little potency against PDK2 (pyruvate dehydrogenase kinase isoform 2) or BDP (BCKD phosphatase) even at concentrations as high as 1 mM (<10% inhibition). Shown to effectively reduce E1-α Ser293 phosphorylation with concomitant BCKDC activity upregulation in multiple tissues in mice (EDmax =160 mg/kg via i.p.; 60 min) in vivo, resulting in significant downregulation of serum BCAA (branched-chain amino acid) Leu/Ile and Val levels. Pharmacokinetic studies reveal good stability in vitro (half-life = 3.1 h and 6.8 h using murine liver S9 preparation or murine hepatocytes, respectively) and low clearance in vivo (CL/F = 0.113 mL/min; 40 mg/kg i.p.), however the compound does not penetrate tissues efficiently (VZ/F = 20.8 mL; 40 mg/kg i.p.) and high dosages are recommended for mice treatment.
A cell-permeable chlorophenylpropionate compound that is superior to its structural analog 4PB (Cat. No. 567616) as an inhibitor against mitochondrial branched-chain α-ketoacid dehydrogenase complex (BCKDC) regulatory kinase BDK (BCKD kinase; IC50 = 6.3 vs. 53.1 M) due to much optimized affinity toward the BDK N-terminal allosteric site (Kd = 2.4 vs. 5.7 M), effectively blocking BDK substrate access by preventing BDK interaction with the homo-24-meric dihydrolipoyltransferase BCKDC E2 component, while exhibiting little potency against PDK2 or BCKD phosphatase BDP even at concentrations as high as 1 mM (<10% inhibition). Shown to effectively reduce E1-α Ser293 phosphorylation with concomitant BCKDC activity upregulation in multiple tissues in mice (EDmax =160 mg/kg via i.p.) in vivo. Despite good stability and low in vivo clearance , high doses are recommended for mice treatment due to low tissue penetration efficiency.

生化/生理作用

Cell permeable: yes
Reversible: yes
Primary Target
BDK

包装

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

重悬

Use only fresh DMSO for reconstitution.
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 1 month at -20°C.

其他说明

Tso, S.C., et al. 2013. Proc. Natl. Acad. Sci. USA110, 9728.

法律信息

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

基本信息

经验(实验)分子式C9H9ClO2
分子量184.62

产品性质

质量水平100
测定≥98% (HPLC)
形式oil
manufacturer/tradenameCalbiochem®
储存条件OK to freeze
desiccated
protect from light
颜色clear colorless
溶解性DMSO: 100 mg/mL
储存温度−20℃

安全信息

储存分类代码11 - Combustible Solids
WGKWGK 3
闪点(F)Not applicable
闪点(C)Not applicable

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