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Merck
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Key Documents

5.05602

Sigma-Aldrich

BDK Inhibitor II, (S)-CPP

Sinônimo(s):

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

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About This Item

Fórmula empírica (Notação de Hill):
C9H9ClO2
Número CAS:
Peso molecular:
184.62
Código UNSPSC:
12352200
NACRES:
NA.77

Ensaio

≥98% (HPLC)

Nível de qualidade

forma

oil

fabricante/nome comercial

Calbiochem®

condição de armazenamento

OK to freeze
desiccated
protect from light

cor

clear colorless

solubilidade

DMSO: 100 mg/mL

temperatura de armazenamento

−20°C

Descrição geral

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.
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.

Ações bioquímicas/fisiológicas

Cell permeable: yes
Primary Target
BDK
Reversible: yes

Embalagem

Packaged under inert gas

Advertência

Toxicity: Standard Handling (A)

Reconstituição

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

Outras notas

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

Informações legais

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

Código de classe de armazenamento

11 - Combustible Solids

Classe de risco de água (WGK)

WGK 3

Ponto de fulgor (°F)

Not applicable

Ponto de fulgor (°C)

Not applicable


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