AVN-944 (also known as VX-944) is an orally active, potent, selective, noncompetitive, and specific inhibitor of IMPDH (inosine monophosphate dehydrogenase). IMPDH is an essential rate-limiting enzyme in de novo guanine nucleotide synthesis. Additionally, AVN-944 acts as an inhibitor of arenavirus RNA synthesis, blocking arenavirus infection. It exhibits broad anti-cancer activities and is applicable to research on multiple myeloma (MM) and acute myeloid leukemia (AML) [1][2][3].
体内研究
AVN-944 (Orally, at doses ranging from 0 to 150 mg/kg, twice daily) significantly prolongs the median survival time of leukemia model mice [2].
体外研究
AVN-944 inhibits the growth of human multiple myeloma (MM) cell lines in a dose-dependent manner, with concentrations ranging from 0 to 1 μM, in a 48-hour period[1].
AVN-944 (800 nM, 0-72 h) triggers apoptosis in MM cell lines via a caspase-independent pathway involving Bax/AIF/Endo G [1].
AVN-944 (0-200 nM) potentiates the cytotoxic effects of Doxorubicin and Melphalan [1].
AVN-944 suppresses the proliferation of human MV-4-11 and murine Ba/F3-Flt3-ITD-dependent cell lines, with IC50 values of 26 and 30 nM, respectively [2].
AVN-944 (0-32 μM, 48 h) exhibits potent activity against arenavirus infection at low doses (7.5 μM) with minimal cytotoxicity [3].
AVN-944 (0-6.4 μM, 48 h) does not affect the viability of peripheral blood mononuclear cells (PBMNCs) [1].
AVN-944 细胞实验
Cell Line
Concentration
Treated Time
Description
References
K562 cells
1 µM
8 to 24 h
To study the effect of MG132 on AVN-944-induced nucleostemin degradation, results showed that MG132 almost completely prevented the loss of nucleostemin protein.
Cancer Res. 2009 Apr 1;69(7):3004-12
U2OS cells
1 µM
8 to 24 h
To study the effect of AVN-944 on nucleostemin protein, results showed that the degradation of nucleostemin protein could be reversed by withdrawal of AVN-944 and addition of guanosine.
Cancer Res. 2009 Apr 1;69(7):3004-12
NB4 cells
1 µM
4 to 24 h
To study the effect of AVN-944 on nucleolar protein nucleostemin, results showed that nucleostemin protein was reduced at 4 hours and nearly absent at 8 hours, while nucleophosmin and nucleolin protein levels remained unchanged.
Cancer Res. 2009 Apr 1;69(7):3004-12
PC-3 cells
5 μM
3 days
AVN944 inhibited proliferation of PC-3 cells and induced S-phase cell cycle block.
Int J Cancer. 2008 Nov 15;123(10):2294-302
DU145 cells
5 μM
3 days
AVN944 inhibited proliferation of DU145 cells and induced S-phase cell cycle block.
Int J Cancer. 2008 Nov 15;123(10):2294-302
CWR22Rv1 cells
5 μM
3 days
AVN944 inhibited proliferation of CWR22Rv1 cells and induced S-phase cell cycle block.
Int J Cancer. 2008 Nov 15;123(10):2294-302
LNCaP cells
5 μM
3 days
AVN944 inhibited proliferation of LNCaP cells and induced G1 phase cell cycle arrest.
Int J Cancer. 2008 Nov 15;123(10):2294-302
Vero76 cells
7.5 μM
48 h
To evaluate the inhibitory effect of AVN-944 on Tacaribe virus infection, results showed that 7.5 μM AVN-944 significantly reduced virus titers (>90%) with minimal cytotoxicity.
Antiviral Res. 2018 Sep;157:140-150
BSR-T7/5 cells
1.6 μM
48 h
To evaluate the inhibitory effect of AVN-944 on viral RNA synthesis, results showed that 1.6 μM AVN-944 significantly reduced reporter activity to background levels with no pronounced cytotoxicity.
Antiviral Res. 2018 Sep;157:140-150
16HBE cells
0.18 μM
72 h
Inhibited NC H1N1 virus replication with EC50 of 0.18 μM
J Virol. 2020 Mar 17;94(7):e02149-19
MDCK cells
0.21 μM
48 h
Inhibited BIRFLU virus replication with EC50 of 0.21 μM
J Virol. 2020 Mar 17;94(7):e02149-19
Human A549 cells
0.07 μM (GFP), 0.13 μM (Scarlet)
24 h
To evaluate the inhibitory activity of AVN-944 against recombinant vaccinia virus (rVACV). Results showed that AVN-944 significantly inhibited rVACV with low EC50 values.
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