Gemcitabine

A synthetic pyrimidine nucleoside prodrug that works by ihibiting the enzyme ribonucleotide reductase (RNR) and blocking the creation of new DNA; a chemotherapy agent for treatment of a number of types of cancer.Chemotherapeutic Agents Approved (In Vitro) :Gemcitabine (purchased from MedChem Express, 0.003-1 μM; 3 days) kills both mouse and human senescent cells effectively and potently.Gemcitabine inhibits the growth of BxPC-3, Mia Paca-2, PANC-1, PL-45 and AsPC-1 cells with IC50s of 37.6, 42.9, 92.7, 89.3 and 131.4 nM, respectively. (In Vivo) :Gemcitabine can be administered via endotracheal spray in rats without marked toxicity with a maximum tolerated dose of 4 mg/kg once a week for 9 weeks. The toxicity of Gemcitabine is lower via lung than oral administration at dosages of 2, 4, and 6 mg/kg.Treatment of the LSL-KrasG12D/+; LSL-Trp53R172H; Pdx-1-Cre mice with either Gemcitabine (50 mg/kg, i.p.) or the combination DMAPT/Gemcitabine significantly increases the median survival time by more than 30 days compared to the placebo group (254.5 or 255 days vs. 217.5 days, respectively) .