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alvocidib + irinotecan
- Development stage
- Phase 2
- Lead developer
- National Cancer Institute
- Modality
- Small Molecules
- Administration
- Intravenous
01
Overview
alvocidib + irinotecan is a combination therapy regimen consisting of the cyclin-dependent kinase (CDK) inhibitor alvocidib and the topoisomerase I inhibitor irinotecan. Alvocidib, a semi-synthetic flavonoid, primarily targets CDK9, which leads to the depletion of short-lived survival proteins like MCL-1, thereby sensitizing cancer cells to apoptosis. Irinotecan is a camptothecin derivative that functions as a cytotoxic chemotherapy agent by stabilizing the complex between DNA and topoisomerase I, causing double-strand DNA breaks during replication. This combination was specifically investigated by the National Cancer Institute (NCI) in a Phase II clinical trial for patients with advanced p53 wild-type gastric adenocarcinoma and gastroesophageal junction adenocarcinoma to determine if the synergistic effect of CDK inhibition and DNA damage could improve clinical outcomes compared to irinotecan monotherapy.
- Other names
- flavopiridol + irinotecanalvocidib + irinotecan hydrochlorideflavopiridol + irinotecan hydrochloride
02
Targets
CDK9 (Cyclin-dependent kinase 9)TOP1 (DNA Topoisomerase I)PIK3CA (Phosphoinositide 3-kinase alpha)MAPK12 (Mitogen-activated protein kinase 12)
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