PEN-866 + fluorouracil + folinic acid

This drug is a **combination therapy** of three agents: - **PEN-866** is a miniature drug conjugate consisting of a small molecule that binds **heat shock protein 90 (HSP90)**, conjugated via a cleavable linker to **SN-38**, the active metabolite of irinotecan and an inhibitor of **topoisomerase I**. PEN-866 selectively accumulates in tumor tissue, leading to sustained release of SN-38 and resultant DNA damage and apoptosis[1][2][6][7]. - **Fluorouracil (5-FU)** is an antimetabolite that inhibits thymidylate synthase, disrupting DNA and RNA synthesis. - **Folinic acid (leucovorin)** stabilizes the binding of 5-FU to thymidylate synthase, enhancing cytotoxicity. This combination is under investigation for the treatment of advanced solid tumors, especially **pancreatic cancer and colorectal cancer**. The rationale is enhanced anti-tumor activity by combining a targeted ADC-like DNA-damaging agent (PEN-866) with standard chemotherapeutic backbone regimens[2][3].

Other names

5-fluorouracil + leucovorin + PEN-866