PNU112455A hydrochloride is a competitive inhibitor of the ATP sites of CDK2 and CDK5, with the Km values for the ATP sites of CDK2 and CDK5 being 3.6 and 3.2μM, respectively [1]. CDK5 is a multifunctional kinase physiologically involved in proliferation, invasion, angiogenesis, genome instability and metabolism in the development of cancers [2].
In vivo, PNU112455A (150mg/kg/day; i.p.) was administered to mice subcutaneously injected with Hepa 1-6 cells for 4 days. This treatment effectively upregulated the level of PD-L1 in tumor cells, promoted the response to anti-PD-1 immunotherapy, and prolonged the survival time of mice with liver cancer tumors[2].
References:
[1] Clare PM, et al. The cyclin-dependent kinases cdk2 and cdk5 act by a random, anticooperative kinetic mechanism. J Biol Chem. 2001 Dec 21;276(51):48292-9.
[2] Zhang R, Wang J, Du Y, et al. CDK5 destabilizes PD-L1 via chaperon-mediated autophagy to control cancer immune surveillance in hepatocellular carcinoma[J]. Journal for Immunotherapy of Cancer, 2023, 11(11): e007529.
PNU112455A hydrochloride是CDK2和CDK5的ATP位点的竞争性抑制剂，其对CDK2和CDK5中ATP位点的Km值分别为3.6μM和3.2μM[1]。CDK5是一种多功能激酶，在癌症的发展过程中参与细胞增殖、侵袭、血管生成、基因组不稳定性和代谢等生理过程[2]。
在体内，PNU112455A（150mg/kg/day, i.p.）治疗皮下注射Hepa 1-6细胞的小鼠4天，有效上调肿瘤细胞中PD-L1的水平，促进抗PD-1免疫疗法的反应，并延长荷瘤肝癌小鼠的存活时间 [2]。