Therapeutic Targets Database
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TTD Target ID: TTDS00062

Target Information
NameInosine-5'-monophosphate dehydrogenase    
Type of targetSuccessful target    
SynonymsIMP dehydrogenase    
IMPD    
IMPDH    
Inosine dehydrogenase    
NAD-dependent inosine monophosphate dehydrogenase    
Probable inosine-5'-monophosphate dehydrogenase IMD1    
SOI12    
Superoxide-inducible protein 12    
DiseaseCancer, unspecific
[ICD9: 140-229   ICD10: C00-C96]
[1][2][3]
Hepatitis C
[ICD9: 070.4, 070.5, 070.70   ICD10: B17.1, B18.2]
[4]
Immunosuppression[5][3][6]
Infections
[ICD9: 001-139   ICD10: A00-B99]
[7]
Influenza A virus infection
[ICD9: 001-139, 042-075, 487, 488   ICD10: A00-B99, A80-A99, B00-B34, J10, J11]
[8]
Leukemia, unspecified
[ICD9: 208.9   ICD10: C91-C95]
[9]
Lung cancer
[ICD9: 162   ICD10: C33-C34]
[10]
Malaria
[ICD9: 084   ICD10: B50-B54]
[11]
Microbial infections
[ICD9: 001-139   ICD10: A00-B99]
[12][13]
Parasitic diseases[14]
Severe acute respiratory syndrome[15]
Trichomoniasis
[ICD9: 131   ICD10: A59]
[16]
Trichomoniasis
[ICD9: 131   ICD10: A59]
[14][17][16]
Tritrichomonial infection
[ICD9: 001-139   ICD10: A00-B99]
[14][17][16]
Viral infection, unspecified
[ICD9: 001-139, 042-075   ICD10: A00-B99, A80-A99, B00-B34]
[6][12][3]
Drug(s)MercaptopurineApprovedAcute lymphatic leukemia[18]
MizoribineApprovedHyperuricemia[19][4]
RibavirinApprovedHepatitis C and respiratory tract infections[20][21]
TiazofurinApprovedCancer[22][23][10]
ViramidinePhase III completedVirus Infection[24]
BioChemical ClassOxidoreductases acting on the CH-OH group of donors    
EC NumberEC 1.1.1.205
PathwayDrug metabolism - other enzymes
Metabolic pathways
Purine metabolism
UniProt IDO96387
P06981
P49058
P50097
PDB Structure1AK5; 1LRT; 1ME7; 1ME8; 1ME9; 1MEH; 1MEI; 1MEW; 1PVN.    
SequenceMASGWKADEVFGGVMSYTYDVIICMPGYIDFALSDIDLTNNMTDNITLKTPVISSPMDTV TGHKMSIALALSGGLGVIHNNMSIEKQIEEVKKVKRFENGFIFDPYTFSPEHTVADVLET KNRVGYKSYPITVDGKVGSKLVGIITGIDYLYLTNKSMKIGDIMTTDVVTGSYPINLSDA NKVLCDEKKSVLPIVNKNNELIALVCRNDMHKNRIFPHASKSQNKQLIVGASISTREHDL ERANQLIKNMIDVICIDSSQGNSIYQIDTIKKIKSAHPDIPIIGGNVVTSQQAKNLIDAG ADVLRIGMGSGSICTTQDVCAVGRAQGTAVYHVSKYAHTRNIKTIADGGIKNSGNIVKAL SLGADFVMLGNLLAATEESCSEYYFENNVRLKIYRGMGSMEAMYNKGFNSKSRYLVDERK NEYTDENIDEIKVSQGVSASLVDKGSVLNLIPHLFKAVKHGFQSMGIRNIPELHSKLYSG DIRFDVRSFNTIKEGKVSDNLIFNNKKFTT
Related US Patent6,395,763
6,498,178
6,541,496
6,617,323
6,653,309
Target ValidationClick to Find Target Validation Information.    
Inhibitor6-Cl-IMP[16]
CellCept[19]
Imidazo[4,5-e][1, 4]diazapine nucleotide (I)[13]
Inosinic Acid[25]
Mercaptopurine[18]
Mizoribine[19][4]
Mycophenolic acid [26]
Mycophenolic acid glucuronide[27]
Ribavirin[20][21]
Selenazofurin[22]
TAD[28]
Tiazofurin[22][23][10]
VX-148[5]
VX-497[19]
Viramidine[24]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1The chemistry of nicotinamide adenine dinucleotide (NAD) analogues containing C-nucleosides related to nicotinamide riboside. Curr Med Chem. 2002 Apr;9(7):733-41. To Reference
Ref 23-cyanoindole-based inhibitors of inosine monophosphate dehydrogenase: synthesis and initial structure-activity relationships. Bioorg Med Chem Lett. 2003 Oct 20;13(20):3557-60. To Reference
Ref 3Novel guanidine-based inhibitors of inosine monophosphate dehydrogenase. Bioorg Med Chem Lett. 2002 Oct 21;12(20):2931-4. To Reference
Ref 4Cofactor mimics as selective inhibitors of NAD-dependent inosine monophosphate dehydrogenase (IMPDH)--the major therapeutic target. Curr Med Chem. 2004 Apr;11(7):887-900. To Reference
Ref 5Characterization of pharmacological efficacy of VX-148, a new, potent immunosuppressive inosine 5'-monophosphate dehydrogenase inhibitor. J Pharmacol Exp Ther. 2002 Sep;302(3):1272-7. To Reference
Ref 6IMP dehydrogenase: the dynamics of drug selectivity. Nucleic Acids Res Suppl. 2003;(3):97-8. To Reference
Ref 7Crystal structure at 2.4 A resolution of Borrelia burgdorferi inosine 5'-monophosphate dehydrogenase: evidence of a substrate-induced hinged-lid motion by loop 6. Biochemistry. 2000 Apr 18;39(15):4533-42. To Reference
Ref 8Mechanism and specificity of action of ribavirin. Antimicrob Agents Chemother. 1979 Jun;15(6):747-53. To Reference
Ref 9IMP dehydrogenase : structural aspects of inhibitor binding. Curr Med Chem. 1999 Jul;6(7):519-36. To Reference
Ref 10Relationships between the cytotoxicity of tiazofurin and its metabolism by cultured human lung cancer cells. J Clin Invest. 1985 Jan;75(1):175-82. To Reference
Ref 11Mechanism-Based Inhibitors: Development of a High Throughput Coupled Enzyme Assay to Screen for Novel Antimalarials. J Biomol Screen. 1999;4(4):187-192. To Reference
Ref 12IMP dehydrogenase: mechanism of action and inhibition. Curr Med Chem. 1999 Jul;6(7):545-60. To Reference
Ref 13A potent "fat base" nucleotide inhibitor of IMP dehydrogenase. Biochemistry. 1998 Aug 25;37(34):11949-52. To Reference
Ref 14Tritrichomonas foetus: a strategy for structure-based inhibitor design of a protozoan inosine-5'-monophosphate dehydrogenase. Exp Parasitol. 1997 Nov;87(3):203-11. To Reference
Ref 15Ribavirin in the treatment of SARS: A new trick for an old drug? CMAJ. 2003 May 13;168(10):1289-92. To Reference
Ref 16Identification of the IMP binding site in the IMP dehydrogenase from Tritrichomonas foetus. Biochemistry. 1995 Oct 24;34(42):13889-94. To Reference
Ref 17Crystal structure of Tritrichomonas foetus inosine-5'-monophosphate dehydrogenase and the enzyme-product complex. Biochemistry. 1997 Sep 2;36(35):10666-74. To Reference
Ref 18Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol. 2008 Aug;64(8):753-67. Epub 2008 May 28. To Reference
Ref 19VX-497: a novel, selective IMPDH inhibitor and immunosuppressive agent. J Pharm Sci. 2001 May;90(5):625-37. To Reference
Ref 20Treating HCV with ribavirin analogues and ribavirin-like molecules. J Antimicrob Chemother. 2006 Jan;57(1):8-13. Epub 2005 Nov 17. To Reference
Ref 21A randomized, double-blind, placebo-controlled dose-escalation trial of merimepodib (VX-497) and interferon-alpha in previously untreated patients with chronic hepatitis C. Antivir Ther. 2005;10(5):635-43. To Reference
Ref 22In vitro and in vivo antiproliferative activity of IPCAR, a new pyrazole nucleoside analog. Anticancer Res. 1998 Jul-Aug;18(4A):2623-30. To Reference
Ref 23Sequential impact of tiazofurin and ribavirin on the enzymic program of the bone marrow. Cancer Res. 1993 Dec 15;53(24):5982-6. To Reference
Ref 24Antiviral agents active against influenza A viruses. Nat Rev Drug Discov. 2006 Dec;5(12):1015-25. To Reference
Ref 25Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. To Reference
Ref 2621070810 To Reference
Ref 27The apparent inhibition of inosine monophosphate dehydrogenase by mycophenolic acid glucuronide is attributable to the presence of trace quantities of mycophenolic acid. Clin Chem. 1999 Jul;45(7):1047-50. To Reference
Ref 28Crystal structure of a ternary complex of Tritrichomonas foetus inosine 5'-monophosphate dehydrogenase: NAD+ orients the active site loop for catalysis. Biochemistry. 2002 Nov 5;41(44):13309-17. To Reference



 

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