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LY2334737 is an orally available valproic acid ester of gemcitabine, a broad-spectrum antimetabolite with antineoplastic activity. Gemcitabine is converted into the active metabolites difluorodeoxycytidine diphosphate and triphosphate (dFdCDP and dFdCTP) by deoxycytidine kinase. dFdCDP inhibits ribonucleotide reductase, thereby decreasing the deoxynucleotide pool available for DNA replication; dFdCTP is incorporated into DNA, resulting in premature termination of DNA replication and eventually the induction of apoptosis.
In vivo: Oral treatment of xenograft models with 3.2 mg/kg LY2334737 once a day for 21 days showed greater tumor growth inhibition of CES2 transfectant than the mock transfectant (P ≤ 0.001).
| Molecular Weight | 389.39 |
| Formula | C17H25F2N3O5 |
| CAS Number | 892128-60-8 |
| Form | Solid |
| Solubility (25°C) | DMSO 10 mM |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related DNA/RNA Synthesis Products |
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| Clofarabine
Clofarabine inhibits the enzymatic activities of ribonucleotide reductase (IC50 = 65 nM) and DNA polymerase. |
| Gemcitabine Hydrochloride
Gemcitabine (Gemzar, LY188011) inhibits DNA synthesis with an IC50 of 0.06 µM. |
| Nelarabine
Nelarabine is a novel purine antimetabolite antineoplastic agent. |
| Mizoribine
Mizoribine (Bredinin) is an imidazole nucleoside and an immunosuppressive agent with an IC50 of approximately 100 μM. Mizoribine inhibits replication of SARS-CoV with IC50s of 3.5 μg/mL and 16 μg/mL for SARS-CoV Frankfurt-1 and SARS-CoV HKU39849, respectively. |
| Capecitabine
Capecitabine is an orally-administered chemotherapeutic agent. Capecitabine is a precursor, that is enzymatically converted to 5-fluorouracil in the tumor, where it inhibits DNA synthesis and slows growth of tumor tissue. Capecitabine may inhibit cytochrome CYP2C9 enzyme, and therefore increase levels of substrates such as phenytoin and other substrates of CYP2C9. |
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