PDK-IN-1

PDK-IN-1 (compound 7o) is a pyruvate dehydrogenase kinase (PDK) inhibitor. PDK-IN-1 shows IC50 values of 0.03 and 0.1 μM for PDK1 and HSP90, respectively. PDK-IN-1 targets PDH/PDK axis thus reducing efficiently the tumor mass[1].

Signaling Pathways >> Metabolic Enzyme/Protease >> PDHK

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> HSP

Signaling Pathways >> Cell Cycle/DNA Damage >> HSP

IC50: 0.03 ± 0.005 μM (PDK1); 0.1 μM (HSP90)[1]

PDK-IN-1 (compound 7o) 对 PSN-1 和 BxPC-3 胰腺细胞系显示出 2D 细胞毒活性，IC50 值分别为 0.1 ± 0.04 和 1.0 ± 0.2 μM。 PDK-IN-1 还显示出 3D 细胞毒活性，IC50 值分别为 3.3 ± 0.2 和 11.9 ± 1.1 μM[1]。

PDK-IN-1 (compound 7o) (20 mg/kg，腹腔注射，每天一次) 在减少肿瘤质量方面比顺铂 (HY-17394) 略微更有效[1]。 PDK-IN-1 显著降低 Lewis 肺癌 (LLC) 小鼠的 PDH 磷酸化[1]。 Animal Model: LLC-bearing C57BL mice[1] Dosage: 20 mg/kg Administration: IP, daily, days 7-14 Result: Reduced more tumor mass than cisplatin (HY-17394) (tumor inhibition by 86 and 84% for compound 7o and cisplatin, respectively). Induced a body weight loss much lower than that induced by cisplatin (HY-17394) and gemcitabine (HY-17026).

[1]. Pecoraro C, et al. 1,2,4-Amino-triazine derivatives as pyruvate dehydrogenase kinase inhibitors: Synthesis and pharmacological evaluation. Eur J Med Chem. 2023 Mar 5;249:115134.