gemcitabine   Click here for help

GtoPdb Ligand ID: 4793

Synonyms: gemcitabine hydrochloride | Gemzar®
Approved drug PDB Ligand
gemcitabine is an approved drug (FDA (1996))
Compound class: Synthetic organic
Comment: Gemcitabine is a nucleoside analogue chemotherapeutic. Chemically, the hydrogen atoms on the 2' carbon of deoxycytidine are replaced by fluorine atoms.
2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 3
Rotatable bonds 2
Topological polar surface area 110.6
Molecular weight 263.07
XLogP 0.14
No. Lipinski's rules broken 0
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Canonical SMILES OCC1OC(C(C1O)(F)F)n1ccc(nc1=O)N
Isomeric SMILES OC[C@H]1O[C@H](C([C@@H]1O)(F)F)n1ccc(nc1=O)N
InChI InChI=1S/C9H11F2N3O4/c10-9(11)6(16)4(3-15)18-7(9)14-2-1-5(12)13-8(14)17/h1-2,4,6-7,15-16H,3H2,(H2,12,13,17)/t4-,6-,7-/m1/s1
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Summary of Clinical Use Click here for help
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 Click here for help
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].