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[CAS NO. 297730-17-7] AVN-944
| Ships within | Stock | Price | Qty | Total |
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| Catalog: | HY-13560 |
| Brand: | MCE |
| CAS: | 297730-17-7 |
Overview
| MDL | MFCD22200574 |
|---|---|
| Molecular Weight | 477.51 |
| Molecular Formula | C25H27N5O5 |
| SMILES | O=C(O[C@@H](CC#N)CC)N[C@H](C1=CC=CC(NC(NC2=CC=C(C3=CN=CO3)C(OC)=C2)=O)=C1)C |
2 Publications Citing Use of MCE
Summary
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 [1] [2] [3] .
In Vitro
AVN-944 (0-1 μM, 48 h) inhibits growth of human multiple myeloma (MM) cell lines in a dose-dependent manner
[1]
.
AVN-944 (800 nM, 0-72 h) induces
apoptosis
in MM cell lines via a caspase-independent, Bax/AIF/Endo G pathway
[1]
.
AVN-944 (0-200 nM) enhances the cytotoxicity of
Doxorubicin
(HY-15142A) and
Melphalan
(HY-17575)
[1]
.
AVN-944 inhibits the proliferation of the human MV-4-11 and murine Ba/F3-Flt3-ITD-dependent cell lines with IC
50
values of 26 and 30 nM, respectively
[2]
.
AVN-944 (0-32 μM, 48 h) shows good activity against arenavirus infection at low doses (7.5 μM) with less cytotoxicity
[3]
.
AVN-944 (0-6.4 μM, 48 h) does not reduce the viability of peripheral blood mononuclear cells (PBMNCs)
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay [1]
| 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 (IC 50 ) 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 IC 50 values similar to the parental drug-sensitive cell lines. |
Apoptosis Analysis [1]
| 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 [1]
| Cell Line: | MM.1S and RPMI8226 cells |
| Concentration: | 800 nM |
| Incubation 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 [1]
| 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. |
In Vivo
AVN-944 (0-150 mg/kg, Orally, twice daily) significantly increases the median survival time of leukemia model mice [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Balb/c mice (leukemia model, using Ba/F3 cells transduced with an activating human Flt-3 mutation injected into mice) [2] |
| 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. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00273936 | Vertex Pharmaceuticals Incorporated |
Acute Leukemia|Chronic Leukemia|Multiple Myeloma|Hodgkin´s Lymphoma|Non-Hodgkin´s Lymphoma|Waldenstrom´s Macroglobulinemia
|
January 2006 | Phase 1 |
| NCT00923728 | Vertex Pharmaceuticals Incorporated|National Cancer Institute (NCI) |
Refractory Solid Tumors
|
April 2009 | Not Applicable |
| NCT00493441 | Vertex Pharmaceuticals Incorporated |
Pancreatic Cancer
|
June 2007 | Phase 2 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 100 mg/mL ( 209.42 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.0942 mL | 10.4710 mL | 20.9420 mL |
| 5 mM | 0.4188 mL | 2.0942 mL | 4.1884 mL |
| 10 mM | 0.2094 mL | 1.0471 mL | 2.0942 mL |
-
1.
-
2.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (5.24 mM); Clear solution
References
- [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.
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