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HomeProduct name listAVN-944

AVN-944

AVN-944 Structural

What is AVN-944?

Description

AVN944 is a selective, noncompetitive inhibitor of inosine-5''-monophosphate dehydrogenase (IMPDH; Ki = 6-10 nM for both human IMPDH isoforms), a rate-limiting enzyme involved in the de novo synthesis of purine nucleotides. Inhibition of IMPDH results in disruption of DNA and RNA synthesis, inhibition of cell proliferation, and the induction of apoptosis. AVN944 has been shown to inhibit the proliferation of multiple myeloma cells in vitro by inducing caspase-independent apoptosis. It is also reported to have antitumor properties in androgen-sensitive and androgen-independent prostate cancer cells in vitro.

The Uses of AVN-944

AVN-944 is a novel inosine monophosphate dehydrogenase (IMPDH) inhibitor. It has antiproliferative effects and might be combined with other agents for treatment of human prostate cancer.This compound is suitable for pyruvate dehydrogenase (PDH) related research.

Enzyme inhibitor

This orally available antineoplastic agent (FW = 310.36 g/mol; CAS 297730-17-7), also known as VX-944 and (R)-1-cyanobutan-2-yl-(S)-1-(3- (3-(3-methoxy-4-(oxazol-5-yl)phenyl)ureido)phenyl)ethyl)carbamate, inhibits inosine 5’-monophosphate dehydrogenase (IMPDH), the enzyme catalyzing the conversion of IMP into XMP, leading to the biosynthesis of GMP, GDP, GTP, and ultimately dGTP. IMPDH is overexpressed in some cancer cells, particularly in hematological malignancies, and AVN944 appears to have a selective cytotoxic effect on cancer cells. Reduction of GTP in normal cells results in a temporary slowing of cell growth only.AVN944 treatment results in dose-dependent cell growth inhibition in all studied prostate cancer cells, independently of their androgen sensitivity. AVN944 treatment arrests LNCaP cells in G1-phase and and androgen independent 22Rv1, DU145 and PC-3 cells in S-phase. AVN-944 treatment leads to the rapid disappearance of nucleostemin, a positive regulator of cell proliferation that is highly expressed in a variety of stem cells, tumors, and tumor cell lines.

Properties of AVN-944

Boiling point: 597.4±50.0 °C(Predicted)
Density  1.277±0.06 g/cm3(Predicted)
storage temp.  Store at -20°C
solubility  DMSO:PBS (pH 7.2) (1:3):0.25(Max Conc. mg/mL);0.52(Max Conc. mM)
DMF:30.0(Max Conc. mg/mL);62.83(Max Conc. mM)
form  A crystalline solid
pka 11.38±0.46(Predicted)
color  White to off-white

Safety information for AVN-944

Computed Descriptors for AVN-944

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