4-Amino-1-[3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-2-oxolanyl]-2-pyrimidinone

개요Gemcitabine is an anticancer nucleoside analog that inhibits the growth of HL-60 promyelocytic leukemia cells with an LC50 value of 40 nM. It inhibits the growth of MX-1 mammary, CX-1, HC-1, GC3, and VRC5 colon, LX-1, Calu-6, and NCI-H460 lung, and HS766T, PaCa-2, PANC-1, and BxPC-3 pancreatic cancer tumors in mouse xenograft models (45-93% inhibition). Gemcitabine is a prodrug that is metabolized to a diphosphate and triphosphate form in cells. The triphosphate form is incorporated into DNA which induces masked chain termination and cell death. By specifically inhibiting growth arrest and DNA damage inducible protein 45 a (Gadd45a), a key mediator of active DNA demethylation, gemcitabine, at concentrations ranging from 34 to 134 nM, inhibits repair-mediated DNA demethylation in a methylation-sensitive reporter assay. Gemcitabine also has broad antiretroviral activity, decreasing MuLV cell infectivity, a murine AIDS model, in cell culture (EC50 = ~1.5 nM) and inhibits the progression of murine AIDS in vivo at a dose of 1-2 mg/kg per day.

용도Gemcitabine(Gemzar) belongs to the group of medicines called antimetabolites. It is used alone or in combination with other medicines to treat cancer of the breast, ovary, pancreas, and lung. Gemcitabine interferes with the growth of cancer cells, which a

일반 설명The drug is available as the hydrochloride salt in 200- and1,000-mg lyophilized single-dose vials for IV use.Gemcitabine is used to treat bladder cancer, breast cancer,pancreatic cancer, and NSCLC. Gemcitabine is a potent radiosensitizer,and it increases the cytotoxicity of cisplatin.The mechanism of action of this fluorine-substituted deoxycytidineanalog involves inhibition of DNA synthesis andfunction via DNA chain termination. The triphosphatemetabolite is incorporated into DNA inhibiting severalDNA polymerases and incorporated into RNA inhibitingproper function of mRNA. Resistance can occur because ofdecreased expression of the activation enzyme deoxycytidinekinase or decreased drug transport as well as increasedexpression of catabolic enzymes. Drug oral bioavailabilityis low because of deamination within the GI tract, and thedrug does not cross the blood-brain barrier. Metabolism bydeamination to 2', 2'-difluorouridine (dFdU) is extensive.Drug toxicity includes myelosuppression, fever, malaise,chills, headache, myalgias, nausea, and vomiting.