Target Information

Target General Infomation
Target ID
T89360
Former ID
TTDS00063
Target Name
Inosine-5'-monophosphate dehydrogenase 2
Gene Name
IMPDH2
Synonyms
IMP dehydrogenase 2; IMPD 2; IMPDH-II; IMPDH2
Target Type
Successful
Disease Organ transplant rejection [ICD9: 279.5, 996; ICD10: D89.8, T86]
Pemphigus vulgaris [ICD9: 694.4; ICD10: L10.0]
Function
Catalyzesthe conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate- limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors.
BioChemical Class
Short-chain dehydrogenases reductases
Target Validation
T89360
UniProt ID
P12268
EC Number
EC 1.1.1.205
Sequence
MADYLISGGTSYVPDDGLTAQQLFNCGDGLTYNDFLILPGYIDFTADQVDLTSALTKKIT
LKTPLVSSPMDTVTEAGMAIAMALTGGIGFIHHNCTPEFQANEVRKVKKYEQGFITDPVV
LSPKDRVRDVFEAKARHGFCGIPITDTGRMGSRLVGIISSRDIDFLKEEEHDCFLEEIMT
KREDLVVAPAGITLKEANEILQRSKKGKLPIVNEDDELVAIIARTDLKKNRDYPLASKDA
KKQLLCGAAIGTHEDDKYRLDLLAQAGVDVVVLDSSQGNSIFQINMIKYIKDKYPNLQVI
GGNVVTAAQAKNLIDAGVDALRVGMGSGSICITQEVLACGRPQATAVYKVSEYARRFGVP
VIADGGIQNVGHIAKALALGASTVMMGSLLAATTEAPGEYFFSDGIRLKKYRGMGSLDAM
DKHLSSQNRYFSEADKIKVAQGVSGAVQDKGSIHKFVPYLIAGIQHSCQDIGAKSLTQVR
AMMYSGELKFEKRTSSAQVEGGVHSLHSYEKRLF
Drugs and Mode of Action
Drug(s) Mycophenolate mofetil Drug Info Approved Organ transplant rejection [1], [2]
Mycophenolate mofetil Drug Info Phase 3 Pemphigus vulgaris [1], [2]
Inhibitor 1-(3-cyano-1-methyl-1H-indol-6-yl)-3-phenylurea Drug Info [3]
1-methoxy-3-(3-(pyridin-4-yl)-1H-indol-6-yl)urea Drug Info [3]
1-methyl-1H-indole-3-carbaldehyde Drug Info [4]
1-methyl-1H-indole-3-carbonitrile Drug Info [3]
1-methyl-1H-indole-3-carboxamide Drug Info [4]
2-Benzyl-6-methoxy-5-oxazol-5-yl-1H-indole Drug Info [5]
2-methyl-3-(pyridin-4-yl)-1H-indol-6-amine Drug Info [4]
2-methyl-3-(pyridin-4-yl)-1H-indole Drug Info [4]
3-(3-cyano-1H-indol-6-yl)-1-methyl-1-phenylurea Drug Info [3]
3-(furan-3-yl)-1-methyl-1H-indole Drug Info [4]
3-(furan-3-yl)-1H-indole Drug Info [4]
3-(pyridin-4-yl)-1H-indol-6-amine Drug Info [4]
3-(pyridin-4-yl)-1H-indol-7-amine Drug Info [4]
3-(pyridin-4-yl)-1H-indole Drug Info [3]
3-(thiophen-3-yl)-1H-indol-6-amine Drug Info [4]
3-methoxy-4-(oxazol-5-yl)aniline Drug Info [4]
6-bromo-1-methyl-3-(pyridin-4-yl)-1H-indole Drug Info [4]
6-bromo-3-(pyridin-4-yl)-1H-indole Drug Info [4]
6-Chloropurine Riboside, 5'-Monophosphate Drug Info [6]
6-Methoxy-5-oxazol-5-yl-2-phenyl-1H-indole Drug Info [5]
6-phenyl-3-(pyridin-4-yl)-1H-indole Drug Info [3]
C2-MAD Drug Info [7]
C4-MAD Drug Info [7]
Ethyl 3-(pyridin-4-yl)-1H-indole-6-carboxylate Drug Info [3]
Inosinic Acid Drug Info [6]
Mycophenolate mofetil Drug Info [8]
Mycophenolic bis(sulfonamide) Drug Info [9]
Mycophenolic hydroxamic acid Drug Info [10]
N-benzyl-9-oxo-9,10-dihydroacridine-3-carboxamide Drug Info [11]
Nicotinamide-Adenine-Dinucleotide Drug Info [6]
Selenazole-4-Carboxyamide-Adenine Dinucleotide Drug Info [6]
Tiazofurin adenine dinucleotide Drug Info [12]
Pathways
BioCyc Pathway Purine nucleotides degradation
Urate biosynthesis/inosine 5&#039
-phosphate degradation
Guanosine nucleotides de novo biosynthesis
Superpathway of purine nucleotide salvage
Purine nucleotides de novo biosynthesis
Guanosine ribonucleotides de novo biosynthesis
KEGG Pathway Purine metabolism
Drug metabolism - other enzymes
Metabolic pathways
PANTHER Pathway De novo purine biosynthesis
Reactome Purine ribonucleoside monophosphate biosynthesis
References
REF 1Emerging drugs for idiopathic thrombocytopenic purpura in adults. Expert Opin Emerg Drugs. 2008 Jun;13(2):237-54.
REF 2(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6831).
REF 3Bioorg Med Chem Lett. 2006 May 1;16(9):2539-42. Epub 2006 Feb 17.Novel indole inhibitors of IMPDH from fragments: synthesis and initial structure-activity relationships.
REF 4Bioorg Med Chem Lett. 2006 May 1;16(9):2535-8. Epub 2006 Feb 17.Low molecular weight indole fragments as IMPDH inhibitors.
REF 5Bioorg Med Chem Lett. 2003 Apr 7;13(7):1273-6.Novel indole-based inhibitors of IMPDH: introduction of hydrogen bond acceptors at indole C-3.
REF 6How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
REF 7Novel mycophenolic adenine bis(phosphonate) analogues as potential differentiation agents against human leukemia. J Med Chem. 2002 Jan 31;45(3):703-12.
REF 8Clinical pipeline report, company report or official report of Roche (2009).
REF 9Bioorg Med Chem. 2008 Aug 1;16(15):7462-9. Epub 2008 Jun 10.Bis(sulfonamide) isosters of mycophenolic adenine dinucleotide analogues: inhibition of inosine monophosphate dehydrogenase.
REF 10Bioorg Med Chem. 2010 Nov 15;18(22):8106-11. Epub 2010 Sep 18.Structure-activity relationships for inhibition of inosine monophosphate dehydrogenase and differentiation induction of K562 cells amongthe mycophenolic acid derivatives.
REF 11J Med Chem. 2007 Jul 26;50(15):3730-42. Epub 2007 Jun 22.Acridone-based inhibitors of inosine 5'-monophosphate dehydrogenase: discovery and SAR leading to the identification of N-(2-(6-(4-ethylpiperazin-1-yl)pyridin-3-yl)propan-2-yl)-2- fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide (BMS-566419).
REF 12J Med Chem. 2007 Dec 27;50(26):6685-91. Epub 2007 Nov 27.Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylases for cancer treatment.

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