Drug intelligence / Profile preview

AZD0156 + irinotecan + fluorouracil + folinic acid

Development stage
Unknown
Lead developer
AstraZeneca
Modality
Small Molecules
Administration
Oral (AZD0156), Intravenous (irinotecan, Fluorouracil, Folinic Acid)
01

Overview

**AZD0156 + irinotecan + fluorouracil + folinic acid** is an experimental multi-drug combination consisting of AZD0156 (a potent, selective inhibitor of ATM kinase), irinotecan (a topoisomerase I inhibitor), fluorouracil (a thymidylate synthase inhibitor), and folinic acid (a cofactor that enhances the efficacy of fluorouracil). AZD0156 impedes DNA damage repair by inhibiting ATM, thereby sensitizing cancer cells to chemotherapeutic agents that induce DNA damage. Irinotecan generates DNA single-strand breaks that become double-strand breaks in replicating cells; fluorouracil inhibits thymidylate synthase, disrupting DNA synthesis; folinic acid increases binding of fluorouracil metabolites to thymidylate synthase, further enhancing cytotoxicity. This combination is being investigated primarily for advanced solid tumors and colorectal cancer, targeting DNA damage response pathways to achieve synergistic anti-tumor effects, especially in tumors with specific DDR mutations[2][3][4][5].

Other names
5-FU
02

Targets

ATM (Ataxia telangiectasia mutated protein)TOP1 (DNA Topoisomerase I)ATR (ATR serine/threonine kinase)TS (Thymidylate synthase)

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