22difluorodeoxycytidine

2',2'-Difluoro-2'-deoxycytidine, commonly known as gemcitabine, is a nucleoside analog used as a chemotherapeutic agent. It is an analog of deoxycytidine in which two fluorine atoms replace the hydroxyl group at the 2' position of the sugar, giving 2',2'-difluoro-2'-deoxycytidine.

Gemcitabine is taken up by cells and phosphorylated by deoxycytidine kinases to the active forms dFdCMP, dFdCDP, and dFdCTP. The triphosphate form, dFdCTP, competes with the natural nucleotide dCTP and becomes incorporated into DNA, leading to masked chain termination and inhibition of DNA synthesis. In addition, dFdCDP inhibits ribonucleotide reductase, lowering intracellular deoxynucleotide pools and enhancing the drug’s antimetabolite effects.

Pharmacokinetically, gemcitabine is administered intravenously and has a rapid plasma clearance with a short initial half-life; its cytotoxic effects are largely mediated by intracellular phosphorylation. It is primarily eliminated renally, with metabolites excreted in urine.

Indications and clinical use include treatment of pancreatic cancer, often in combination regimens such as with nab-paclitaxel, as well as non-small cell lung cancer and certain urothelial or breast cancers in various regimens. Its use is determined by tumor type, stage, and patient factors, and regimens are chosen to balance efficacy with toxicity.

Common adverse effects include myelosuppression (neutropenia and thrombocytopenia), fever, fatigue, nausea, vomiting, rash, and elevated liver enzymes. Infusion-related reactions and mucositis can occur, and renal function can influence drug exposure. gemcitabine has a well-established role in solid tumor chemotherapy, often as part of combination therapy.