Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTL7C8Q)

DTT Name Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1)
Synonyms
Superoxide-inducible protein 12; SOI12; Probable inosine-5'-monophosphate dehydrogenase IMD1; NAD-dependent inosine monophosphate dehydrogenase; Inosine dehydrogenase; IMPDH-I; IMPDH 1; IMPDH; IMPD1; IMPD 1; IMPD; IMP dehydrogenase 1; IMP dehydrogenase
Gene Name IMPDH1
DTT Type
Successful target
 [1]
Related Disease
Breast cancer [ICD-11: 2C60-2C6Y]
Hepatitis virus infection [ICD-11: 1E50-1E51]
Mature B-cell lymphoma [ICD-11: 2A85]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Transplant rejection [ICD-11: NE84]
BioChemical Class
CH-OH donor oxidoreductase
UniProt ID
IMDH1_HUMAN
TTD ID
T40111
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 1.1.1.205
Sequence
MADYLISGGTGYVPEDGLTAQQLFASADGLTYNDFLILPGFIDFIADEVDLTSALTRKIT
LKTPLISSPMDTVTEADMAIAMALMGGIGFIHHNCTPEFQANEVRKVKKFEQGFITDPVV
LSPSHTVGDVLEAKMRHGFSGIPITETGTMGSKLVGIVTSRDIDFLAEKDHTTLLSEVMT
PRIELVVAPAGVTLKEANEILQRSKKGKLPIVNDCDELVAIIARTDLKKNRDYPLASKDS
QKQLLCGAAVGTREDDKYRLDLLTQAGVDVIVLDSSQGNSVYQIAMVHYIKQKYPHLQVI
GGNVVTAAQAKNLIDAGVDGLRVGMGCGSICITQEVMACGRPQGTAVYKVAEYARRFGVP
IIADGGIQTVGHVVKALALGASTVMMGSLLAATTEAPGEYFFSDGVRLKKYRGMGSLDAM
EKSSSSQKRYFSEGDKVKIAQGVSGSIQDKGSIQKFVPYLIAGIQHGCQDIGARSLSVLR
SMMYSGELKFEKRTMSAQIEGGVHGLHSYEKRLY
Function
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. Catalyzes the 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.
KEGG Pathway
Purine metabolism (hsa00230 )
Drug metabolism - other enzymes (hsa00983 )
Metabolic pathways (hsa01100 )
Nucleotide metabolism (hsa01232 )
Reactome Pathway
Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817 )
Potential therapeutics for SARS (R-HSA-9679191 )
Azathioprine ADME (R-HSA-9748787 )
Neutrophil degranulation (R-HSA-6798695 )
BioCyc Pathway
MetaCyc:HS02896-MON

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
5 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Mercaptopurine DMTM2IK Acute lymphoblastic leukaemia 2A85 Approved [1]
Merimepodib DM0HS92 Breast cancer 2C60-2C65 Approved [2], [3]
Mizoribine DMW6F0S Transplant rejection NE84 Approved [2], [4]
Ribavirin DMEYLH9 Hepatitis C virus infection 1E51.1 Approved [5], [6]
Tiazofurin DM5JWV9 Solid tumour/cancer 2A00-2F9Z Approved [7], [8], [9]
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2 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Viramidine DMJFNR9 Hepatitis C virus infection 1E51.1 Phase 3 [10]
VX-944 DME321B Solid tumour/cancer 2A00-2F9Z Phase 2 [3]
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57 Patented Agent(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Carbamide derivative 10 DM9O56W N. A. N. A. Patented [3]
Carbamide derivative 11 DMK7DJR N. A. N. A. Patented [3]
Carbamide derivative 4 DM5V2D9 N. A. N. A. Patented [3]
Carbamide derivative 5 DM951HL N. A. N. A. Patented [3]
Carbamide derivative 6 DMORBE3 N. A. N. A. Patented [3]
Carbamide derivative 7 DMWKXN4 N. A. N. A. Patented [3]
Carbamide derivative 8 DMZ3FJO N. A. N. A. Patented [3]
Carbamide derivative 9 DMY06VC N. A. N. A. Patented [3]
Mycophenolic acid/nucleotide derivative 1 DMOZTUE N. A. N. A. Patented [3]
Mycophenolic acid/nucleotide derivative 10 DMHD8RK N. A. N. A. Patented [3]
Mycophenolic acid/nucleotide derivative 11 DMXWOAG N. A. N. A. Patented [3]
Mycophenolic acid/nucleotide derivative 12 DM47L9Q N. A. N. A. Patented [3]
Mycophenolic acid/nucleotide derivative 2 DMAT9NE N. A. N. A. Patented [3]
Mycophenolic acid/nucleotide derivative 3 DM5UX7B N. A. N. A. Patented [3]
Mycophenolic acid/nucleotide derivative 4 DMEHMKY N. A. N. A. Patented [3]
Mycophenolic acid/nucleotide derivative 5 DM74UP5 N. A. N. A. Patented [3]
Mycophenolic acid/nucleotide derivative 6 DMGFORB N. A. N. A. Patented [3]
Mycophenolic acid/nucleotide derivative 7 DMC27TO N. A. N. A. Patented [3]
Mycophenolic acid/nucleotide derivative 8 DMWGIJS N. A. N. A. Patented [3]
Mycophenolic acid/nucleotide derivative 9 DMYQTLK N. A. N. A. Patented [3]
PMID28074661-Compound-US20100022547C80 DMQW470 N. A. N. A. Patented [3]
PMID28074661-Compound-US20100022547C81 DMM9E1U N. A. N. A. Patented [3]
PMID28074661-Compound-US20100022547C82 DM94MT3 N. A. N. A. Patented [3]
PMID28074661-Compound-US20100022547C83 DM18LO7 N. A. N. A. Patented [3]
PMID28074661-Compound-US20100022547C86 DMONEJ4 N. A. N. A. Patented [3]
PMID28074661-Compound-US20100022547C87 DM8E702 N. A. N. A. Patented [3]
PMID28074661-Compound-US20100022547C88 DMNUR8E N. A. N. A. Patented [3]
PMID28074661-Compound-US20120264760C80 DM75QVW N. A. N. A. Patented [3]
PMID28074661-Compound-US20120264760C81 DMH249S N. A. N. A. Patented [3]
PMID28074661-Compound-US20120264760C82 DM18PRU N. A. N. A. Patented [3]
PMID28074661-Compound-US20120264760C83 DMD7AU3 N. A. N. A. Patented [3]
PMID28074661-Compound-US20120264760C86 DMKFEO4 N. A. N. A. Patented [3]
PMID28074661-Compound-US20120264760C87 DM85XKT N. A. N. A. Patented [3]
PMID28074661-Compound-US20120264760C88 DMIKRCM N. A. N. A. Patented [3]
PMID28074661-Compound-US20128202889C90 DMEJ4LW N. A. N. A. Patented [3]
PMID28074661-Compound-US20158969342C84 DM1QUN0 N. A. N. A. Patented [3]
PMID28074661-Compound-US20169447134C85 DMMYH82 N. A. N. A. Patented [3]
PMID28074661-Compound-WO2009018344C78 DMFORUW N. A. N. A. Patented [3]
PMID28074661-Compound-WO2009018344C79 DM64QNL N. A. N. A. Patented [3]
Quinazolinone derivative 1 DMSU1PC N. A. N. A. Patented [3]
Quinazolinone derivative 2 DM0XVQY N. A. N. A. Patented [3]
Quinolone derivative 1 DME6P7T N. A. N. A. Patented [3]
Urea and carbamate bioisostere derivative 10 DMWNR8I N. A. N. A. Patented [3]
Urea and carbamate bioisostere derivative 11 DMAP6YS N. A. N. A. Patented [3]
Urea and carbamate bioisostere derivative 13 DM6BJEW N. A. N. A. Patented [3]
Urea and carbamate bioisostere derivative 14 DMDP09N N. A. N. A. Patented [3]
Urea and carbamate bioisostere derivative 15 DM3SQUD N. A. N. A. Patented [3]
Urea and carbamate bioisostere derivative 16 DMRLC4X N. A. N. A. Patented [3]
Urea and carbamate bioisostere derivative 18 DM7PSB1 N. A. N. A. Patented [3]
Urea and carbamate bioisostere derivative 2 DMRTJSC N. A. N. A. Patented [3]
Urea and carbamate bioisostere derivative 3 DMPXVWE N. A. N. A. Patented [3]
Urea and carbamate bioisostere derivative 4 DM5GZNS N. A. N. A. Patented [3]
Urea and carbamate bioisostere derivative 5 DM02ZM4 N. A. N. A. Patented [3]
Urea and carbamate bioisostere derivative 6 DMP29I0 N. A. N. A. Patented [3]
Urea and carbamate bioisostere derivative 7 DM2GPLQ N. A. N. A. Patented [3]
Urea and carbamate bioisostere derivative 9 DMIYD41 N. A. N. A. Patented [3]
VX-148 DML32R8 Psoriasis vulgaris EA90 Patented [11], [3]
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⏷ Show the Full List of 57 Patented Agent(s)
1 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Phenacetin DMRQAM0 Analgesia MB40.8 Withdrawn from market [12]
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4 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
6-Cl-IMP DMNTDFV Discovery agent N.A. Investigative [13]
Inosinic Acid DMLR86H Discovery agent N.A. Investigative [14]
Selenazofurin DMKSIVL Discovery agent N.A. Investigative [7]
TAD DMCIEQO Discovery agent N.A. Investigative [15]
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References

1 Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol. 2008 Aug;64(8):753-67.
2 VX-497: a novel, selective IMPDH inhibitor and immunosuppressive agent. J Pharm Sci. 2001 May;90(5):625-37.
3 Inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitors: a patent and scientific literature review (2002-2016).Expert Opin Ther Pat. 2017 Jun;27(6):677-690.
4 Cofactor mimics as selective inhibitors of NAD-dependent inosine monophosphate dehydrogenase (IMPDH)--the major therapeutic target. Curr Med Chem. 2004 Apr;11(7):887-900.
5 Treating HCV with ribavirin analogues and ribavirin-like molecules. J Antimicrob Chemother. 2006 Jan;57(1):8-13.
6 A 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.
7 In vitro and in vivo antiproliferative activity of IPCAR, a new pyrazole nucleoside analog. Anticancer Res. 1998 Jul-Aug;18(4A):2623-30.
8 Sequential impact of tiazofurin and ribavirin on the enzymic program of the bone marrow. Cancer Res. 1993 Dec 15;53(24):5982-6.
9 Relationships between the cytotoxicity of tiazofurin and its metabolism by cultured human lung cancer cells. J Clin Invest. 1985 Jan;75(1):175-82.
10 Antiviral agents active against influenza A viruses. Nat Rev Drug Discov. 2006 Dec;5(12):1015-25.
11 Characterization 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.
12 A potent "fat base" nucleotide inhibitor of IMP dehydrogenase. Biochemistry. 1998 Aug 25;37(34):11949-52.
13 Identification of the IMP binding site in the IMP dehydrogenase from Tritrichomonas foetus. Biochemistry. 1995 Oct 24;34(42):13889-94.
14 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
15 Crystal 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.