RX-3117 (fluorocyclopentenyl cytosine): a novel specific antimetabolite for selective cancer treatment.

RX-3117 (fluorocyclopentenyl cytosine): a novel specific antimetabolite for selective cancer treatment. Expert Opin Investig Drugs. 2019 Mar 16;:1-12 Authors: Balboni B, El Hassouni B, Honeywell RJ, Sarkisjan D, Giovannetti E, Poore J, Heaton C, Peterson C, Benaim E, Lee YB, Kim DJ, Peters GJ Abstract INTRODUCTION: RX-3117 is an oral, small molecule cytidine analog anticancer agent with an improved pharmacological profile relative to gemcitabine and other nucleoside analogs. The agent has excellent activity against various cancer cell lines and xenografts including gemcitabine-resistant variants and it has excellent oral bioavailability; it is not a substrate for the degradation enzyme cytidine deaminase. RX-3117 is being evaluated at a daily oral schedule of 700 mg (5 days/week for 3 weeks) which results in plasma levels in the micromolar range that have been shown to be cytotoxic to cancer cells. It has shown clinical activity in refractory bladder cancer and pancreatic cancer. Areas covered: The review provides an overview of the relevant market and describes the mechanism of action, main pharmacokinetic/pharmacodynamic features and clinical development of this investigational small molecule. Expert opinion: RX-3117 is selectively activated by uridine-cytidine kinase 2 (UCK2), which is expressed only in tumors and has a dual mechanism of action: DNA damage and inhibition of DNA methyltransferase 1 (DNMT1). Because of its tumor sel...
Source: Expert Opinion on Investigational Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research