TG003

TG003 is a small molecule benzothiazole derivative that acts as a potent and selective inhibitor of the CDC2-like kinase (CLK) family, specifically targeting CLK1, CLK2, and CLK4. It also exhibits inhibitory activity against the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). By inhibiting CLK-mediated phosphorylation of serine/arginine-rich (SR) proteins, TG003 modulates alternative pre-mRNA splicing, a process frequently dysregulated in cancer and genetic disorders. In preclinical studies, TG003 has been shown to promote exon skipping in Duchenne muscular dystrophy (DMD) to restore dystrophin expression and rescue splicing defects in Seckel syndrome. In oncology, it has demonstrated anti-proliferative and pro-apoptotic effects in prostate, gastric, and ovarian cancer models, often by altering the splicing of cancer-associated genes. While widely used as a chemical probe in research, its metabolic instability has led to the development of more stable analogs like TG693 for potential clinical applications.

Other names

(Z)-1-(3-ethyl-5-methoxy-2,3-dihydrobenzothiazol-2-ylidene)propan-2-one