A novel small molecule inhibitor of p38⍺ MAP kinase augments cardiomyocyte cell cycle entry in response to direct cell cycle stimulation.

ABSTRACT:

Background and purpose

Myocardial infarction (MI) is the leading cause of mortality globally due in part to the limited ability of cardiomyocytes (CMs) to regenerate. Recently, we demonstrated that overexpression of four-cell cycle factors, CDK1, CDK4, cyclin B1 and cyclin D1 (4F), induced cell division in ~20% of the post-mitotic CMs overexpressed 4F. The current study aims to identify a small molecule that augments 4F-induced CM cycle induction.

Experimental approach, key results

Screening of small molecules with a potential to augment 4F-induced cell-cycle induction in 60-day-old mature human induced pluripotent cardiomyocytes (hiPS-CMs) revealed N-(4,6-Dimethylpyridin-2-yl)-4-(pyridine-4-yl)piperazine-1-carbothioamide (NDPPC), which activates cell cycle progression in 4F

SUBMITTER: Abouleisa RRE 

PROVIDER: S-EPMC10726296 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature