AVN944

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

AVN-944(VX-944) 是一种针对人 IMPDH 的选择性非竞争性酶抑制剂，对 IMPDH1/IMPDH2 的 Ki 为 6-10 nM。

AVN-944(VX-944) is a selective, noncompetitive inhibitor of the enzyme directed against human IMPDH with Ki of 6-10 nM for IMPDH1/IMPDH2.(In Vitro):AVN-944 (0-1 μM, 48 h) inhibits growth of human multiple myeloma (MM) cell lines in a dose-dependent manner.AVN-944 (800?nM, 0-72?h) induces apoptosis in MM cell lines via a caspase-independent, Bax/AIF/Endo G pathway.AVN-944 (0-200 nM) enhances the cytotoxicity of Doxorubicin (HY-15142A) and Melphalan (HY-17575).AVN-944 inhibits the proliferation of the human MV-4-11 and murine Ba/F3-Flt3-ITD-dependent cell lines with IC50 values of 26 and 30 nM, respectively.AVN-944 (0-32 μM, 48?h) shows good activity against arenavirus infection at low doses (7.5?μM) with less cytotoxicity.AVN-944 (0-6.4 μM, 48 h) does not reduce the viability of peripheral blood mononuclear cells (PBMNCs).(In Vivo):AVN-944 (0-150 mg/kg, Orally, twice daily) significantly increases the median survival time of leukemia model mice.

AVN-944 (0-1 μM, 48 h) inhibits growth of human multiple myeloma (MM) cell lines in a dose-dependent manner.AVN-944 (800?nM, 0-72?h) induces apoptosis in MM cell lines via a caspase-independent, Bax/AIF/Endo G pathway.AVN-944 (0-200 nM) enhances the cytotoxicity of Doxorubicin (HY-15142A) and Melphalan (HY-17575).AVN-944 inhibits the proliferation of the human MV-4-11 and murine Ba/F3-Flt3-ITD-dependent cell lines with IC50 values of 26 and 30 nM, respectively. AVN-944 (0-32 μM, 48?h) shows good activity against arenavirus infection at low doses (7.5?μM) with less cytotoxicity.AVN-944 (0-6.4 μM, 48 h) does not reduce the viability of peripheral blood mononuclear cells (PBMNCs). Cell Proliferation Assay Cell Line:RPMI8226, MM.1S, and U266 cells Concentration:0, 100, 200, 300, 400, 600, 1000 nM Incubation Time:48?h Result:Significantly inhibited the growth of RPMI8226, MM.1S, and U266 cells in a dose-dependent fashion, with 50% inhibition (IC50) values at 48?h of 450, 450, and 600?nM, respectively. Inhibited growth of drug-resistant cell lines, including Doxorubicin (Dox)-resistant RPMI8226-Dox40, Melphalan (Mel) resistant RPMI8226-LR5, and Dex (Dexamethasone) resistant MM.1R cells, with IC50 values similar to the parental drug-sensitive cell lines.Apoptosis AnalysisCell Line:MM.1S and RPMI8226 cells Concentration:800?nM Incubation Time:48 and 72?h Result:Induced apoptosis in MM cell lines.Western Blot Analysis Cell Line:MM.1S and RPMI8226 cells Concentration:800?nMIncubation Time:12, 24, 48?h Result:Induced modest cleavage of caspase 3, 8 and 9 in MM.1S cells and RPMI8226 cells. Markedly upregulated Bax and Bak, without significant changes in Bcl-2, Mcl-1, XIAP, and Bad. Observed translocation of mitochondrial proapoptotic proteins, apoptosis-inducing factor (AIF) and endonuclease G (Endo G) to cytosolic fractions.Cell Cytotoxicity Assay Cell Line:MM.1S cells, MM.1S cells cultured with BMSCs Concentration:0, 50, 200 nM Incubation Time:24?h Result:Enhanced the cytotoxicity of of Doxorubicin and Melphalan in MM.1S cells. Additive effects were also observed in MM.1S cells cultured with BMSCs derived from MM patient.

AVN-944 (0-150 mg/kg, Orally, twice daily) significantly increases the median survival time of leukemia model mice. Animal Model:Balb/c mice (leukemia model, using Ba/F3 cells transduced with an activating human Flt-3 mutation injected into mice) Dosage:75 or 150 mg/kg Administration:Orally, twice dailyResult:Provided a significant increase in median survival time. Three of the 12 mice treated with 150 mg/kg AVN-944 were still alive on Day 35 when the study was terminated.

AVN 944 | AVN-944 | AVN944 | VX944 | VX 944 | VX-944.

Metabolic Enzyme/Protease

Dehydrogenase

IMPDH

Cancer

——

297730-17-7

477.51

C25H27N5O5

>98% (HPLC)

DMSO: 58 mg/mL

O=C(O[C@H](CC)CC#N)N[C@H](C1=CC=CC(NC(NC2=CC=C(C3=CN=CO3)C(OC)=C2)=O)=C1)C

(R)-1-cyanobutan-2-yl ((S)-1-(3-(3-(3-methoxy-4-(oxazol-5-yl)phenyl)ureido)phenyl)ethyl)carbamate

(-20℃)

With Ice Pack

≥ 2 years