Plasmodium falciparum cyclin-dependent-like kinase 3 (PfCLK3)

Plasmodium falciparum cyclin-dependent-like kinase 3 (PfCLK3) is a member of the cyclin-dependent like protein kinase family in P. falciparum, classified within the CMGC kinase superfamily. PfCLK3 plays a crucial role in pre-mRNA splicing and processing, which is essential for the parasite’s development across multiple life stages including asexual blood stages, liver stages, and sexual gametocytes. The kinase is structurally related to eukaryotic cyclin-dependent kinases but exhibits unique properties in Plasmodium, such as its essentiality for survival and regulatory role in gene expression via RNA splicing. PfCLK3 and its inhibitors have emerged as validated antimalarial drug targets, showing curative, prophylactic, and transmission-blocking potential by halting parasite development through the inhibition of gene splicing machinery. Selective inhibitors like TCMDC-135051 have shown multistage activity, high selectivity over human kinases, reduction of essential transcripts, and parasite clearance in preclinical models, supporting their further development as antimalarials.

Other names

CLK3cyclin-dependent-like kinase CLK3Pf3D7_1114700PF11_0156

Inhibition of PfCLK3 blocks pre-mRNA splicing, preventing production of essential parasite transcripts and leading to death of blood and liver stage parasites and transmission stages