PF-07104091 hydrate is a potent and selective inhibitor of CDK2/E1 and GSK3β with Kis of 1.16 and 537.81 nM[1], respectively. PF-07104091 hydrate has antitumor activity against cyclin E1-amplified cancers and is commonly used to treat HR+/HER2- breast cancer and ovarian cancer[2].
PF-07104091 (37-3000nM, 24h) inhibits the expression of biomarkers t-Rb, t-NCL, pRB S8078/811, and p-NCL T84 in OVCAR3 cells[1].PF-07104091(0.01-10mM, 3day) inhibits the proliferation of tumor cells (TOV-21G, HCT116) [3].
PF-07104091 (25、75、175 mpk，25 day; twice per day;PO) inhibits tumor growth (TGI) of OVCAR3 tumors mice[1] .In nude mouse model of HCT116 transplanted tumor, PF-07104091(50 mg/kg, 14 day) reduced tumor volume by nearly 69.81% and tumor weight by nearly 60.16%.[3]
References:
[1].Shen C, Zhang Q, Almaden J, et al. PF-07104091, a first-in-class CDK2-selective inhibitor for the treatment of HR+/HER2-breast cancer and CCNE1 high ovarian cancer[J]. Cancer Research, 2024, 84(6_Supplement): 5709-5709.
[2]. Douglas Carl BEHENNA, et al. Cdk2 inhibitors. WO2020157652A2.
[3]. Liu, Z.; Yang, Y.; Sun, X.; Ma, R.; Zhang, W.; Wang, W.; Yang, G.; Wang, H.; Zhang, J.; Wang, Y.; et al. Discovery of Novel Antitumor Small-Molecule Agent with Dual Action of CDK2/p-RB and MDM2/p53. Molecules 2024, 29, 725.