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Background Information:
AVN-944 (VX-944) is an orally available, uncompetitive small molecule inhibitor of inosine monophosphate dehydrogenase (IMPDH), an enzyme catalyzing the rate limiting step in the biosynthesis of guanine nucleotides. As IMPDH is overexpressed in some cancer cells, particularly in hematological malignancies, thus inhibition of this enzyme will result in depletion of guanine nucleotide pools, cessation of DNA synthesis, cell cycle block at the Gr(1)/S interface and interference with cell division, and induction of apoptosis. The reduction in guanine nucleotide pools will also interfere with the ability of G-coupled proteins to act as intracellular signal transducers.
Reference:
1. D. Floryk, et al., Antiproliferative effects of AVN944, a novel inosine 5-monophosphate dehydrogenase inhibitor, in prostate cancer cells, International Journal of Cancer (2008), 123(10), 2294-2302.
2. J. Hamilton, et al., A phase I dose-ranging study of the pharmacokinetics, pharmacodynamics, safety, and tolerability of AVN944, an IMPDH inhibitor, in healthy male volunteers, Journal of Clinical Pharmacology (2009), 49(1), 30-38.
3. M. Huang, et al., Depletion of guanine nucleotides leads to the Mdm2-dependent proteasomal degradation of nucleostemin, Cancer Research (2009), 69(7), 3004-3012.
APIM050292: AVN944
CAS No.: 297730-17-7.
Molecular Formula: C25H27N5O5•0.35H2O.
Molecular Weight: 483.8.
Purity: >99.5% chem and stereomerical purity (HPLC and Chiral HPLC at 214 and 254 nm).
QC: HPLC-MS, 1HNMR, Chiral HPLC and Quantitative Elemental Analysis.
Solubility: Soluble in DMSO.
Storage: Store at 0°C (short term), -20°C (long term), desiccated.
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