Azenosertib — Investigational Agent
Other · Phase 2 · Zentalis Pharmaceuticals
Mechanism of Action
Azenosertib is an oral, potent, selective inhibitor of WEE1, a kinase that enforces the G2/M cell-cycle checkpoint via inhibitory phosphorylation of CDK1. In tumors with high replication stress—particularly those with TP53 mutations or Cyclin E1 (CCNE1) amplification—WEE1 inhibition abolishes the G2/M checkpoint and drives premature mitotic entry with unrepaired DNA, causing mitotic catastrophe. Azenosertib also increases replication origin firing, depleting nucleotide pools and further amplifying DNA damage. This mechanism is especially relevant to high-grade serous ovarian cancer, which is…
Investigational Indications
- Platinum-resistant high-grade serous ovarian cancer
- Cyclin E1-amplified ovarian and endometrial cancer
- Uterine serous carcinoma
- TP53-mutant solid tumors