品牌	貨號	產品規格	價格(RMB)	庫存（上海）	北京	武漢	南京
源葉(MedMol)	S84817-5mg	99%	￥450.00元	8	-	-	-
源葉(MedMol)	S84817-10mg	99%	￥580.00元	6	-	-	-
源葉(MedMol)	S84817-50mg	99%	￥1970.00元	3	-	-	-

產品介紹

AVN-944 (VX-944) is an orally active, potent, selective, noncompetitive and specific inhibitor of IMPDH (inosine monophosphate dehydrogenase). AVN-944 is an essential rate-limiting enzyme in de novo guanine nucleotide synthesis. AVN-944 is also an inhibitor of arenavirus RNA synthesis, and blocks arenavirus infection. AVN-944 has broad anti-cancer activities, and can be used for multiple myeloma (MM) and acute myeloid leukemia (AML) research

產品描述： AVN-944 (VX-944) is an orally active, potent, selective, noncompetitive and specific inhibitor of IMPDH (inosine monophosphate dehydrogenase). AVN-944 is an essential rate-limiting enzyme in de novo guanine nucleotide synthesis. AVN-944 is also an inhibitor of arenavirus RNA synthesis, and blocks arenavirus infection. AVN-944 has broad anti-cancer activities, and can be used for multiple myeloma (MM) and acute myeloid leukemia (AML) research

靶點： Arenavirus;DNA/RNA Synthesis;Apoptosis;Caspase;Bcl-2 Family;Dehydrogenase

體外研究：
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 Analysis Cell 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?nM

體內研究：
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 daily Result: 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.

參考文獻：
1. Zimmermann AG, et al. Inosine-5'-monophosphate dehydrogenase: regulation of expression and role in cellular proliferation and T lymphocyte activation. Prog Nucleic Acid Res Mol Biol. 1998;61:181-209. 2. Huang M, et al. Guanine nucleotide depletion inhibits pre-ribosomal RNA synthesis and causes nucleolar disruption. Leuk Res. 2008 Jan;32(1):131-41. 3. Floryk D, et al. Antiproliferative effects of AVN944, a novel inosine 5-monophosphate dehydrogenase inhibitor, in prostate cancer cells. Int J Cancer. 2008 Nov 15;123(10):2294-302.

溶解性： Soluble in DMSO

保存條件： -20℃

配置溶液濃度參考：

	1mg	5mg	10mg
1 mM	2.094 ml	10.471 ml	20.942 ml
5 mM	0.419 ml	2.094 ml	4.188 ml
10 mM	0.209 ml	1.047 ml	2.094 ml
50 mM	0.042 ml	0.209 ml	0.419 ml

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