Kevetrin

Kevetrin (3-Cyanopropyl carbamimidothioate; 4-Isothioureidobutyronitrile) is an apoptosis inducer that exhibits p53-dependent and p53-independent antitumor activity. In TP53 wild-type models, Kevetrin activates and stabilizes the p53 protein by altering the processing of MDM2, thereby inducing cell cycle arrest and apoptosis. Kevetrin shows higher sensitivity in mutant models. Kevetrin is applicable for the research of various cancers including acute myeloid leukemia and breast cancer^[1]. In Vitro:Kevetrin (85-340 μM; 6-72 h) does not reduce the viability of TP53 wild-type MOLM-13 acute myeloid leukemia (AML) cells, nor does it induce significant apoptosis in these cells^[1].
Kevetrin (85-340 μM; 6-72 h) reduces cell viability and induces apoptosis in TP53-mutant KASUMI-1 acute myeloid leukemia (AML) cells in a dose- and time-dependent manner, with more significant efficacy after repeated administration cycles^[1].
Kevetrin (340 μM; 6 h) alters the expression of MT family genes and several leukemia-related transcriptional regulators in TP53 wild-type MOLM-13 cells and TP53 mutant KASUMI-1 acute myeloid leukemia (AML) cells^[1].
Kevetrin (85-340 μM; 48 h) reduces cell viability in both TP53 wild-type and TP53 mutant AML cell lines, with TP53 mutant cell lines exhibiting higher sensitivity^[1].
Kevetrin (85-340 μM; 24-48 h) induces apoptosis in both TP53 wild-type and TP53 mutant acute myeloid leukemia (AML) cell lines, with TP53 mutant cell lines exhibiting a stronger, dose-dependent apoptotic response^[1].
Kevetrin (85, 170, 340 μM; 24-48 h) induces G0/G1 cell cycle arrest in TP53 wild-type OCI-AML3 cells and TP53-mutant NOMO-1 acute myeloid leukemia (AML) cells, but does not alter the cell cycle progression of TP53 wild-type MOLM-13 cells or TP53-mutant KASUMI-1 AML cells^[1].
Kevetrin (85-340 μM; 48 h) reduces the viability of primary AML cells and induces their apoptosis, exhibits selective cytotoxic activity against blasts, and shows higher sensitivity in primary samples with TP53 mutations^[1].
Kevetrin (340 μM; 48 h) alters a shared core transcriptional program in TP53 wild-type MOLM-13 and TP53-mutant KASUMI-1 acute myeloid leukemia (AML) cells, downregulates key oncogenic pathways such as glycolysis and DNA repair, and upregulates p53 target genes and p53 pathway-associated transcriptional signatures^[1].
Kevetrin (85-340 μM; 48 h) upregulates p21 in a dose-dependent manner in TP53 wild-type AML cells, increases the expression level of p53 and promotes its nuclear localization, and also induces the accumulation of p53 in apoptotic cells, with a stronger induction effect of p53 in TP53-mutant AML cell lines^[1].