THZ-P1-2

THZ-P1-2 is a potent and selective PI5P4K inhibitor. THZ-P1-2 covalently targets cysteines on a disordered loop in PI5P4Kα/β/γ with an IC50 of 190 nM for PI5P4Kα. THZ-P1-2 causes autophagy disruption and upregulates TFEB signaling. THZ-P1-2 displays anticancer activity in leukemia cell lines[1].

Research Areas >> Cancer

Signaling Pathways >> Autophagy >> Autophagy

THZ-P1-2 (0.2-11.4 μM) exhibits approximately 75% inhibition of PI-4,5-P2 formation by PI5P4Kα and PI5P4Kγ and 50% inhibition by PI5P4Kβ at a concentration of 0.7 μM[1]. THZ-P1-2 (10-100000 nM; 72 hours) shows modest anti-proliferative activity in all six AML/ALL cell lines with IC50 values in the low micromolar range[1]. Cell Proliferation Assay[1] Cell Line: THP1, SEMK2, OCI/AML-2, HL60, SKM1, NOMO1 cells Concentration: 10-100000 nM Incubation Time: 72 hours Result: Showed anti-proliferative activity in all six AML/ALL cell lines with IC50 values ranging from 0.87 to 3.95 μM.

[1]. Sivakumaren SC, et al. Targeting the PI5P4K Lipid Kinase Family in Cancer Using Covalent Inhibitors. Cell Chem Biol. 2020;27(5):525‐537.e6.