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
Purity
>97% (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/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO:PBS (pH 7.2) (1:3) |
0.3 |
0.52 |
| DMF |
30.0 |
62.83 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
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.
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
