Drug intelligence / Profile preview

folinic acid + irinotecan + oxaliplatin + 5-fluorouracil + gemcitabine + nab-paclitaxel

Development stage
Preclinical
Lead developer
Ipsen
Modality
Small Molecules
Administration
Intravenous
01

Overview

This is a six-drug combination chemotherapy regimen consisting of folinic acid (leucovorin), irinotecan, oxaliplatin, 5-fluorouracil (5-FU), gemcitabine, and nab-paclitaxel. Each component has a distinct mechanism of action targeting various aspects of cancer cell survival and proliferation: - Folinic acid enhances the binding of 5-fluorouracil to thymidylate synthase, increasing its cytotoxicity. - Irinotecan inhibits topoisomerase I, leading to DNA damage during replication. - Oxaliplatin forms DNA crosslinks that inhibit DNA synthesis and transcription. - 5-Fluorouracil is an antimetabolite that inhibits thymidylate synthase and incorporates into RNA/DNA, disrupting their function. - Gemcitabine is a nucleoside analog that inhibits DNA synthesis by incorporation into the growing DNA strand and inhibiting ribonucleotide reductase. - Nab-paclitaxel stabilizes microtubules, preventing their depolymerization during mitosis. This combination brings together two established regimens for advanced pancreatic cancer—FOLFIRINOX (folinic acid/irinotecan/oxaliplatin/fluorouracil) and gemcitabine plus nab-paclitaxel—into one protocol. While both FOLFIRINOX and gemcitabine/nab-paclitaxel are approved first-line therapies for metastatic pancreatic adenocarcinoma individually[1][3][7], there is no evidence from clinical trials or guidelines supporting the use of all six agents simultaneously as a single regimen. The safety profile would be expected to include significant risk for myelosuppression, neuropathy, gastrointestinal toxicity, fatigue, infection risk, among others.

02

Targets

TOP1 (DNA Topoisomerase I)DNATS (Thymidylate synthase)

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