Zotiraciclib — Investigational Agent
Other · Phase 1/2 · National Cancer Institute / Adastra Pharmaceuticals
Mechanism of Action
Zotiraciclib is an oral, brain-penetrant multi-kinase inhibitor of cyclin-dependent kinase 9 (CDK9) along with CDK1/2/7 and JAK2/FLT3. Inhibition of CDK9 suppresses RNA polymerase II C-terminal domain phosphorylation, shutting down transcription of short-lived pro-survival proteins such as MCL-1 and c-MYC, on which glioma cells depend. Depleting MCL-1 lowers the apoptotic threshold and, in IDH-mutant gliomas, exploits metabolic vulnerabilities related to NAD+ and mitochondrial function. Its CNS penetration makes it suitable for primary brain tumors, and it is combined with temozolomide to…
Investigational Indications
- Recurrent IDH-mutant glioma (astrocytoma)
- Recurrent glioblastoma / high-grade glioma
- Recurrent anaplastic astrocytoma