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fluorouracil + leucovorin + oxaliplatin + selinexor

Development stage
Preclinical
Lead developer
Karyopharm Therapeutics
Modality
Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules, Metabolically Activated Prodrugs → Prodrugs/Conditional Activator Small Molecules → Small Molecules, DNA Intercalators/Alkylators → Nucleic Acid-Directed Small Molecules → Small Molecules
Administration
Intravenous, Oral
01

Overview

This is a four-drug combination regimen consisting of fluorouracil, leucovorin, oxaliplatin, and selinexor. Fluorouracil (5-FU) is a pyrimidine analog that inhibits thymidylate synthase, disrupting DNA synthesis in rapidly dividing cells. Leucovorin (folinic acid) enhances the binding of 5-FU to thymidylate synthase, increasing its cytotoxicity. Oxaliplatin is a platinum-based chemotherapeutic agent that forms DNA crosslinks and induces apoptosis in cancer cells[1][2][3][4][5]. Selinexor is an oral selective inhibitor of nuclear export (SINE), specifically targeting exportin 1 (XPO1/CRM1). By inhibiting XPO1, selinexor causes the accumulation of tumor suppressor proteins in the nucleus and promotes apoptosis in malignant cells[6][8][9]. This combination leverages multiple mechanisms—antimetabolite activity from 5-FU/leucovorin, DNA damage from oxaliplatin, and nuclear export inhibition from selinexor—to target cancer cell survival pathways. While FOLFOX (fluorouracil + leucovorin + oxaliplatin) is established for colorectal cancer treatment[3][4], adding selinexor represents an investigational approach aiming to enhance antitumoral efficacy by combining standard chemotherapy with targeted nuclear export inhibition.

02

Targets

XPO1 (Exportin-1)DNATS (Thymidylate synthase)

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