WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200390
CAS#: 297730-17-7
Description: AVN-944 (VX-944) is an orally available, synthetic small molecule with potential antineoplastic activity. AVN944 inhibits inosine monosphosphate dehydrogenase (IMPDH), an enzyme involved in the de novo synthesis of guanosine triphosphate (GTP), a purine molecule required for DNA and RNA synthesis. Inhibition of IMPDH deprives cancer cells of GTP, resulting in disruption of DNA and RNA synthesis, inhibition of cell proliferation, and the induction of apoptosis. AVN944 appears to have a selective effect on cancer cells in that deprivation of GTP in normal cells results in a temporary slowing of cell growth only. IMPDH is overexpressed in some cancer cells, particularly in hematological malignancies.
MedKoo Cat#: 200390
Name: AVN-944
CAS#: 297730-17-7
Chemical Formula: C25H27N5O5
Exact Mass: 477.20122
Molecular Weight: 477.51
Elemental Analysis: C, 62.88; H, 5.70; N, 14.67; O, 16.75
Synonym: AVN 944; AVN-944; AVN944; VX944; VX 944; VX-944.
IUPAC/Chemical Name: (R)-1-cyanobutan-2-yl ((S)-1-(3-(3-(3-methoxy-4-(oxazol-5-yl)phenyl)ureido)phenyl)ethyl)carbamate
InChi Key: GYCPCOJTCINIFZ-OXJNMPFZSA-N
InChi Code: InChI=1S/C25H27N5O5/c1-4-20(10-11-26)35-25(32)28-16(2)17-6-5-7-18(12-17)29-24(31)30-19-8-9-21(22(13-19)33-3)23-14-27-15-34-23/h5-9,12-16,20H,4,10H2,1-3H3,(H,28,32)(H2,29,30,31)/t16-,20+/m0/s1
SMILES Code: 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
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | 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 activity: | The effect of VX-944 on growth of MM cell lines was determined using the MTT assay. VX-944 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. VX-944 also 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 (Figure 1a). Reference: Oncogene. 2005 Sep 1;24(38):5888-96. https://pubmed.ncbi.nlm.nih.gov/15940263/ |
| In vivo activity: | TBD |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO:PBS (pH 7.2) (1:3) | 0.25 | 0.52 | |
| DMF | 30.0 | 62.83 |
The following data is based on the product molecular weight 477.51 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Dunham EC, Leske A, Shifflett K, Watt A, Feldmann H, Hoenen T, Groseth A. Lifecycle modelling systems support inosine monophosphate dehydrogenase (IMPDH) as a pro-viral factor and antiviral target for New World arenaviruses. Antiviral Res. 2018 Sep;157:140-150. doi: 10.1016/j.antiviral.2018.07.009. Epub 2018 Jul 19. PMID: 30031760. 2. Ishitsuka K, Hideshima T, Hamasaki M, Raje N, Kumar S, Podar K, Le Gouill S, Shiraishi N, Yasui H, Roccaro AM, Tai YZ, Chauhan D, Fram R, Tamura K, Jain J, Anderson KC. Novel inosine monophosphate dehydrogenase inhibitor VX-944 induces apoptosis in multiple myeloma cells primarily via caspase-independent AIF/Endo G pathway. Oncogene. 2005 Sep 1;24(38):5888-96. doi: 10.1038/sj.onc.1208739. PMID: 15940263. |
| In vitro protocol: | 1. Dunham EC, Leske A, Shifflett K, Watt A, Feldmann H, Hoenen T, Groseth A. Lifecycle modelling systems support inosine monophosphate dehydrogenase (IMPDH) as a pro-viral factor and antiviral target for New World arenaviruses. Antiviral Res. 2018 Sep;157:140-150. doi: 10.1016/j.antiviral.2018.07.009. Epub 2018 Jul 19. PMID: 30031760. 2. Ishitsuka K, Hideshima T, Hamasaki M, Raje N, Kumar S, Podar K, Le Gouill S, Shiraishi N, Yasui H, Roccaro AM, Tai YZ, Chauhan D, Fram R, Tamura K, Jain J, Anderson KC. Novel inosine monophosphate dehydrogenase inhibitor VX-944 induces apoptosis in multiple myeloma cells primarily via caspase-independent AIF/Endo G pathway. Oncogene. 2005 Sep 1;24(38):5888-96. doi: 10.1038/sj.onc.1208739. PMID: 15940263. |
| In vivo protocol: | TBD |
1: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Mar;31(2):107-46. PubMed PMID: 19455266.
2: Huang M, Itahana K, Zhang Y, Mitchell BS. Depletion of guanine nucleotides leads to the Mdm2-dependent proteasomal degradation of nucleostemin. Cancer Res. 2009 Apr 1;69(7):3004-12. doi: 10.1158/0008-5472.CAN-08-3413. Epub 2009 Mar 24. PubMed PMID: 19318567.
3: Hamilton JM, Harding MW, Genna T, Bol DK. A phase I dose-ranging study of the pharmacokinetics, pharmacodynamics, safety, and tolerability of AVN944, an IMPDH inhibitor, in healthy male volunteers. J Clin Pharmacol. 2009 Jan;49(1):30-8. doi: 10.1177/0091270008325149. Epub 2008 Oct 29. PubMed PMID: 18971325.
4: Floryk D, Thompson TC. 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. doi: 10.1002/ijc.23788. PubMed PMID: 18712736; PubMed Central PMCID: PMC2887704.
5: Chen L, Pankiewicz KW. Recent development of IMP dehydrogenase inhibitors for the treatment of cancer. Curr Opin Drug Discov Devel. 2007 Jul;10(4):403-12. Review. PubMed PMID: 17659481.
6: Huang M, Ji Y, Itahana K, Zhang Y, Mitchell B. Guanine nucleotide depletion inhibits pre-ribosomal RNA synthesis and causes nucleolar disruption. Leuk Res. 2008 Jan;32(1):131-41. Epub 2007 Apr 25. PubMed PMID: 17462731
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