1. Signaling Pathways
  2. Metabolic Enzyme/Protease
  3. PDHK

PDHK (丙酮酸脱氢酶激酶)

Pyruvate dehydrogenase kinase; PDH kinase

丙酮酸脱氢酶 (PDHK) 是葡萄糖降解中不可逆步骤的催化剂,其活性受高度特异性蛋白激酶丙酮酸脱氢酶激酶 (PDHK/PDK) 的调节。PDHK 属于线粒体蛋白激酶家族,与其他真核蛋白激酶不同。PDHK 通过对丙酮酸脱氢酶部分中的三个丝氨酸残基进行磷酸化,使多酶线粒体丙酮酸脱氢酶复合物失活,从而在控制葡萄糖稳态中发挥重要作用。

人类有四种 PDHK 亚型 (1 至 4)。PDHK 亚型在肥胖、糖尿病、心力衰竭和癌症中上调,是这些重要人类疾病的潜在治疗靶点。

Pyruvate dehydrogenase is a catalyst for an irreversible step in the degradation of glucose and its activity is regulated by a highly specific protein kinase, pyruvate dehydrogenase kinase (PDHK/PDK). PDHK belongs to a family of mitochondrial protein kinases unique from other eukaryotic protein kinases. PDHK inactivates the multienzyme mitochondrial pyruvate dehydrogenase complex by the phosphorylation of three seryl residues in the pyruvate dehydrogenase moiety, and thus plays an important role in the control of glucose homeostasis.

There are four isoforms of PDHK (1 to 4) in humans. PDHK isoforms are up-regulated in obesity, diabetes, heart failure, and cancer and are potential therapeutic targets for these important human diseases.

Cat. No. Product Name Effect Purity Chemical Structure
  • HY-170838
    PDHK1-IN-1 Inhibitor
    PDHK1-IN-1 (compound 17) 是 PDHK1 的选择性抑制剂 (IC50=1.5 μM),具有抗癌活性。PDHK1 负调控丙酮酸脱氢酶复合物 (PDC),限制三羧酸 (TCA) 循环和氧化磷酸化。PDHK1 过表达可使代谢向糖酵解依赖性增加转变 (Warburg 效应)。PDHK1-IN-1 能抑制 PDHK1 识别位点 PDC E1α Ser232 的磷酸化,抑制 Ser293 的磷酸化。
    PDHK1-IN-1
  • HY-162586
    PDHK-IN-7 Inhibitor
    PDHK-IN-7 (compound 32) 是丙酮酸脱氢酶激酶的抑制剂,其IC50值为 17 nM。PDHK-IN-7 可激活大鼠肝脏中的 PDH,并对 Zucker 肥胖大鼠具有降糖作用。
    PDHK-IN-7
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