PPIA-IN-1

PPIA-IN-1 is a PPIA inhibitor with a K d value of 0.52 μM. PPIA-IN-1 inhibits the PPIA / MAPK signaling pathway to exert antiproliferative activity. PPIA-IN-1 induces G0/G1 cell cycle arrest in cancer cells. PPIA-IN-1 upregulates the expression of Bax and caspase-3, downregulates Bcl-2 expression, and induces apoptosis in cancer cells. PPIA-IN-1 induces increased ROS levels, DNA damage, endoplasmic reticulum stress, and mitochondrial dysfunction in cancer cells. PPIA-IN-1 exhibits antitumor activity in a mouse colon cancer xenograft model. PPIA-IN-1 can be used for the research of colorectal cancer ^[1].

In Vivo, PPIA-IN-1 (15-45 mg/kg; i.p.; once daily; for 14 consecutive days) exhibits potent, dose-dependent antitumor efficacy in the CT26 colon cancer xenograft model of BALB/c mice^[1].

In Vitro, PPIA-IN-1 (Compound 20b) potently inhibits the proliferation of HeLa, HCT116, MCF-7, SW480, CT26, Panc-1 and HepG-2 cells, with IC₅₀ values of 0.69, 0.51, 1.19, 2.59, 0.86, 3.31 and 2.16 μM^[1]. PPIA-IN-1 (0-1.2 μM; 24 h) reduces the colony-forming ability of HCT116 cells and inhibits cell migration and invasion^[1]. PPIA-IN-1 (0-1.2 μM; 48 h) dose-dependently arrests HCT116 cells at the G0/G1 phase and downregulates the expression of cyclin A2 and CDK4^[1]. PPIA-IN-1 (0-1.2 μM; 48 h) induces apoptosis in HCT116 cells, upregulates the expression of Bax and caspase-3, and downregulates the expression of Bcl-2 protein^[1]. PPIA-IN-1 (0-1.2 μM; 48 h) increases the intracellular ROS level in HCT116 cells^[1]. PPIA-IN-1 (0-1.2 μM; 48 h) inhibits DNA synthesis and proliferation of HCT116 cells, induces cellular DNA damage, and upregulates the expression of γ-H2AX and p53^[1]. PPIA-IN-1 (0.3-1.2 μM; 48 h) dose-dependently activates endoplasmic reticulum stress and upregulates the expression of PERK, ATF4 and CHOP in HCT116 cells^[1].

References:
[1]. Li XJ, et al. Discovery of Novel Oxazolo[4,3- f ]purine Derivatives as Antitumor Agents through PPIA Interaction. J Med Chem. 2025;68(5):5573-5596.