AVN-944
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.
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
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
| Chemical | |
|---|---|
| CAS Num | 297730-17-7 |
| Chemical Formula | C25H27N5O5 |
| Molecular Weight | 477.51 |
| IUPAC Chemical Name | (R)-1-cyanobutan-2-yl ((S)-1-(3-(3-(3-methoxy-4-(oxazol-5-yl)phenyl)ureido)phenyl)ethyl)carbamate |
| Exact Mass | 477.20122 |
| 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. |
| Solubility | Soluble in DMSO, not in water |
| 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 |
| Biological | |
| Targets and Effects | N/A |
| Pathways | Apoptosis |
| Physical | |
| 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). |
| Shelf Life | >2 years if stored properly |
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