Ligand id: 4793

Name: gemcitabine

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 7
Hydrogen bond donors 4
Rotatable bonds 2
Topological polar surface area 108.05
Molecular weight 264.08
XLogP -0.77
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
Gemcitabine in combination with carboplatin is indicated for the treatment of relapsed ovarian cancer and inoperable, locally advanced or metastatic non-small cell lung cancer. Gemcitabine in combination with paclitaxel is used to treat metastatic breast cancer. As a single therapy, gemcitabine is used to treat locally advanced, nonresectable or metastatic adenocarcinoma of the pancreas.
Mechanism Of Action and Pharmacodynamic Effects
Gemcitabine is a nucleoside analogue and its cytotoxicity is correlated with incorporation into genomic DNA and concomitant inhibition of DNA synthesis. Gemcitabine is metabolised by nucleoside kinases to the active diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleosides: Gemcitabine diphosphate inhibits ribonucleotide reductase resulting in a reduction in the concentrations of deoxynucleotides, including dCTP in the cell. Concommitantly the gemcitabine triphosphate is preferentially incorporated into the DNA as a result of the diphosphate induced reduction in the dCTP level. In combination, these actions lead to inability of the cell to synthesise new DNA or repair damaged DNA and cells undergo apoptosis. Gemcitabine is also believed to inhibit topoisomerase I, since mouse leukemia cells with no topoisomerase I are resistant to gemcitabine induced-growth inhibition [3].