Target Information
Target General Information | Top | |||||
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Target ID |
T40111
(Former ID: TTDS00062)
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Target Name |
Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1)
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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
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Gene Name |
IMPDH1
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 5 Target-related Diseases | + | ||||
1 | Breast cancer [ICD-11: 2C60-2C6Y] | |||||
2 | Hepatitis virus infection [ICD-11: 1E50-1E51] | |||||
3 | Mature B-cell lymphoma [ICD-11: 2A85] | |||||
4 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
5 | Transplant rejection [ICD-11: NE84] | |||||
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.
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BioChemical Class |
CH-OH donor oxidoreductase
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UniProt ID | ||||||
EC Number |
EC 1.1.1.205
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Sequence |
MADYLISGGTGYVPEDGLTAQQLFASADGLTYNDFLILPGFIDFIADEVDLTSALTRKIT
LKTPLISSPMDTVTEADMAIAMALMGGIGFIHHNCTPEFQANEVRKVKKFEQGFITDPVV LSPSHTVGDVLEAKMRHGFSGIPITETGTMGSKLVGIVTSRDIDFLAEKDHTTLLSEVMT PRIELVVAPAGVTLKEANEILQRSKKGKLPIVNDCDELVAIIARTDLKKNRDYPLASKDS QKQLLCGAAVGTREDDKYRLDLLTQAGVDVIVLDSSQGNSVYQIAMVHYIKQKYPHLQVI GGNVVTAAQAKNLIDAGVDGLRVGMGCGSICITQEVMACGRPQGTAVYKVAEYARRFGVP IIADGGIQTVGHVVKALALGASTVMMGSLLAATTEAPGEYFFSDGVRLKKYRGMGSLDAM EKSSSSQKRYFSEGDKVKIAQGVSGSIQDKGSIQKFVPYLIAGIQHGCQDIGARSLSVLR SMMYSGELKFEKRTMSAQIEGGVHGLHSYEKRLY Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
HIT2.0 ID | T00RT4 |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 5 Approved Drugs | + | ||||
1 | Mercaptopurine | Drug Info | Approved | Acute lymphoblastic leukaemia | [2], [3] | |
2 | Merimepodib | Drug Info | Approved | Breast cancer | [4] | |
3 | Mizoribine | Drug Info | Approved | Transplant rejection | [5], [6] | |
4 | Ribavirin | Drug Info | Approved | Hepatitis C virus infection | [7], [8] | |
5 | Tiazofurin | Drug Info | Approved | Solid tumour/cancer | [9] | |
Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
1 | Viramidine | Drug Info | Phase 3 | Hepatitis C virus infection | [10] | |
2 | VX-944 | Drug Info | Phase 2 | Solid tumour/cancer | [11] | |
Patented Agent(s) | [+] 1 Patented Agents | + | ||||
1 | VX-148 | Drug Info | Patented | Psoriasis vulgaris | [12] | |
Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
1 | Phenacetin | Drug Info | Withdrawn from market | Analgesia | [13], [14] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 69 Inhibitor drugs | + | ||||
1 | Mercaptopurine | Drug Info | [1] | |||
2 | Merimepodib | Drug Info | [15], [16] | |||
3 | Mizoribine | Drug Info | [15], [17] | |||
4 | Ribavirin | Drug Info | [18], [19] | |||
5 | Tiazofurin | Drug Info | [20], [21], [22] | |||
6 | Viramidine | Drug Info | [23] | |||
7 | VX-944 | Drug Info | [16] | |||
8 | Carbamide derivative 10 | Drug Info | [16] | |||
9 | Carbamide derivative 11 | Drug Info | [16] | |||
10 | Carbamide derivative 4 | Drug Info | [16] | |||
11 | Carbamide derivative 5 | Drug Info | [16] | |||
12 | Carbamide derivative 6 | Drug Info | [16] | |||
13 | Carbamide derivative 7 | Drug Info | [16] | |||
14 | Carbamide derivative 8 | Drug Info | [16] | |||
15 | Carbamide derivative 9 | Drug Info | [16] | |||
16 | Mycophenolic acid/nucleotide derivative 1 | Drug Info | [16] | |||
17 | Mycophenolic acid/nucleotide derivative 10 | Drug Info | [16] | |||
18 | Mycophenolic acid/nucleotide derivative 11 | Drug Info | [16] | |||
19 | Mycophenolic acid/nucleotide derivative 12 | Drug Info | [16] | |||
20 | Mycophenolic acid/nucleotide derivative 2 | Drug Info | [16] | |||
21 | Mycophenolic acid/nucleotide derivative 3 | Drug Info | [16] | |||
22 | Mycophenolic acid/nucleotide derivative 4 | Drug Info | [16] | |||
23 | Mycophenolic acid/nucleotide derivative 5 | Drug Info | [16] | |||
24 | Mycophenolic acid/nucleotide derivative 6 | Drug Info | [16] | |||
25 | Mycophenolic acid/nucleotide derivative 7 | Drug Info | [16] | |||
26 | Mycophenolic acid/nucleotide derivative 8 | Drug Info | [16] | |||
27 | Mycophenolic acid/nucleotide derivative 9 | Drug Info | [16] | |||
28 | PMID28074661-Compound-US20100022547C80 | Drug Info | [16] | |||
29 | PMID28074661-Compound-US20100022547C81 | Drug Info | [16] | |||
30 | PMID28074661-Compound-US20100022547C82 | Drug Info | [16] | |||
31 | PMID28074661-Compound-US20100022547C83 | Drug Info | [16] | |||
32 | PMID28074661-Compound-US20100022547C86 | Drug Info | [16] | |||
33 | PMID28074661-Compound-US20100022547C87 | Drug Info | [16] | |||
34 | PMID28074661-Compound-US20100022547C88 | Drug Info | [16] | |||
35 | PMID28074661-Compound-US20120264760C80 | Drug Info | [16] | |||
36 | PMID28074661-Compound-US20120264760C81 | Drug Info | [16] | |||
37 | PMID28074661-Compound-US20120264760C82 | Drug Info | [16] | |||
38 | PMID28074661-Compound-US20120264760C83 | Drug Info | [16] | |||
39 | PMID28074661-Compound-US20120264760C86 | Drug Info | [16] | |||
40 | PMID28074661-Compound-US20120264760C87 | Drug Info | [16] | |||
41 | PMID28074661-Compound-US20120264760C88 | Drug Info | [16] | |||
42 | PMID28074661-Compound-US20128202889C90 | Drug Info | [16] | |||
43 | PMID28074661-Compound-US20158969342C84 | Drug Info | [16] | |||
44 | PMID28074661-Compound-US20169447134C85 | Drug Info | [16] | |||
45 | PMID28074661-Compound-WO2009018344C78 | Drug Info | [16] | |||
46 | PMID28074661-Compound-WO2009018344C79 | Drug Info | [16] | |||
47 | Quinazolinone derivative 1 | Drug Info | [16] | |||
48 | Quinazolinone derivative 2 | Drug Info | [16] | |||
49 | Quinolone derivative 1 | Drug Info | [16] | |||
50 | Urea and carbamate bioisostere derivative 10 | Drug Info | [16] | |||
51 | Urea and carbamate bioisostere derivative 11 | Drug Info | [16] | |||
52 | Urea and carbamate bioisostere derivative 13 | Drug Info | [16] | |||
53 | Urea and carbamate bioisostere derivative 14 | Drug Info | [16] | |||
54 | Urea and carbamate bioisostere derivative 15 | Drug Info | [16] | |||
55 | Urea and carbamate bioisostere derivative 16 | Drug Info | [16] | |||
56 | Urea and carbamate bioisostere derivative 18 | Drug Info | [16] | |||
57 | Urea and carbamate bioisostere derivative 2 | Drug Info | [16] | |||
58 | Urea and carbamate bioisostere derivative 3 | Drug Info | [16] | |||
59 | Urea and carbamate bioisostere derivative 4 | Drug Info | [16] | |||
60 | Urea and carbamate bioisostere derivative 5 | Drug Info | [16] | |||
61 | Urea and carbamate bioisostere derivative 6 | Drug Info | [16] | |||
62 | Urea and carbamate bioisostere derivative 7 | Drug Info | [16] | |||
63 | Urea and carbamate bioisostere derivative 9 | Drug Info | [16] | |||
64 | VX-148 | Drug Info | [24], [16] | |||
65 | Phenacetin | Drug Info | [25] | |||
66 | 6-Cl-IMP | Drug Info | [26] | |||
67 | Inosinic Acid | Drug Info | [27] | |||
68 | Selenazofurin | Drug Info | [20] | |||
69 | TAD | Drug Info | [28] |
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Co-Targets | Top | |||||
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Co-Targets |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol. 2008 Aug;64(8):753-67. | |||||
REF 2 | URL: 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: 7226). | |||||
REF 3 | S-adenosylmethionine regulates thiopurine methyltransferase activity and decreases 6-mercaptopurine cytotoxicity in MOLT lymphoblasts. Biochem Pharmacol. 2009 Jun 15;77(12):1845-53. | |||||
REF 4 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 022059. | |||||
REF 5 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
REF 6 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
REF 7 | URL: 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: 6842). | |||||
REF 8 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 076192. | |||||
REF 9 | De novo synthesis of two new cytotoxic tiazofurin analogues with modified sugar moieties. Bioorg Med Chem Lett. 2003 Oct 6;13(19):3167-70. | |||||
REF 10 | A phase III study of the safety and efficacy of viramidine versus ribavirin in treatment-na ve patients with chronic hepatitis C: ViSER1 results. Hepatology. 2009 Sep;50(3):717-26. | |||||
REF 11 | ClinicalTrials.gov (NCT00493441) AVN944 in Combination With Gemcitabine for the Treatment of Pancreatic Cancer. U.S. National Institutes of Health. | |||||
REF 12 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013965) | |||||
REF 13 | URL: 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: 7402). | |||||
REF 14 | An epidemiologic study of abuse of analgesic drugs. Effects of phenacetin and salicylate on mortality and cardiovascular morbidity (1968 to 1987)Dubach UC1, Rosner B, St rmer T.Author information1Department of Internal Medicine, Kantonsspital, Basel, Switzerland.AbstractBACKGROUND: Phenacetin abuse is known to produce kidney disease; salicylate use is supposed to prevent cardiovascular disease. We conducted a prospective, longitudinal epidemiologic study to examine the effects of these drugs on cause-specific mortality and on cardiovascular morbidity.METHODS: In 1968 we evaluated a study group of 623 healthy women 30 to 49 years old who had evidence of a regular intake of phenacetin, as measured by urinary excretion of its metabolites, and a matched control group of 621 women. Salicylate excretion was also measured. All subjects were examined over a period of 20 years.RESULTS: Life-table analyses of mortality during the 20 years, with adjustment for the year of birth, cigarette smoking, and length of follow-up, revealed significant differences between the groups in overall mortality (study group vs. control group, 74 vs. 27 deaths; relative risk, 2.2; 95 percent confidence interval, 1.5 to 3.3), deaths due to urologic or renal disease (relative risk, 16.1; 95 percent confidence interval, 3.9 to 66.1), deaths due to cancer (relative risk, 1.9; 95 percent confidence interval, 1.1 to 3.3), and deaths due to cardiovascular disease (relative risk, 2.9; 95 percent confidence interval, 1.5 to 5.5). The relative risk of cardiovascular disease (fatal or nonfatal myocardial infarction, heart failure, or stroke) was 1.8, and the 95 percent confidence interval 1.3 to 2.6. The odds ratio for the incidence of hypertension was 1.6, and the 95 percent confidence interval 1.2 to 2.1. The effects of phenacetin on morbidity and mortality, with adjustment for base-line salicylate excretion, were similar. In contrast, salicylate use had no effect on either mortality or morbidity.CONCLUSIONS: Regular use of analgesic drugs containing phenacetin is associated with an increased risk of hypertension and mortality and morbidity due to cardiovascular disease, as well as an increased riskof mortality due to cancer and urologic or renal disease. The use of salicylates carries no such risk.Comment inThe risks of phenacetin use. [N Engl J Med. 1991]PMID: 1984193 [PubMed - indexed for MEDLINE] Free full textSharePublication Types, MeSH Terms, SubstancesPublication TypesResearch Support, Non-U.S. Gov'tMeSH TermsAdultAgedAspirin/adverse effects*Cardiovascular Diseases/epidemiology*Cardiovascular Diseases/mortalityDose-Response Relationship, DrugFemaleHumansHypertension/epidemiologyKidney Diseases/mortalityLongitudinal StudiesMiddle AgedMortality*Neoplasms/mortalityPhenacetin/adverse effects*Prospective StudiesRiskSubstance-Related Disorders*Urologic Diseases/mortalitySubstancesPhenacetinAspirinLinkOut - more resourcesFull Text SourcesAtypon - PDFAtyponOvid Technologies, Inc.MedicalDrug Abuse - MedlinePlus Health InformationMiscellaneousACETYLSALICYLIC ACID - Hazardous Substances Data BankPHENACETIN - Hazardous Substances Data BankPubMed Commons home N Engl J Med. 1991 Jan 17;324(3):155-60. | |||||
REF 15 | VX-497: a novel, selective IMPDH inhibitor and immunosuppressive agent. J Pharm Sci. 2001 May;90(5):625-37. | |||||
REF 16 | Inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitors: a patent and scientific literature review (2002-2016).Expert Opin Ther Pat. 2017 Jun;27(6):677-690. | |||||
REF 17 | 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. | |||||
REF 18 | Treating HCV with ribavirin analogues and ribavirin-like molecules. J Antimicrob Chemother. 2006 Jan;57(1):8-13. | |||||
REF 19 | 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. | |||||
REF 20 | In vitro and in vivo antiproliferative activity of IPCAR, a new pyrazole nucleoside analog. Anticancer Res. 1998 Jul-Aug;18(4A):2623-30. | |||||
REF 21 | Sequential impact of tiazofurin and ribavirin on the enzymic program of the bone marrow. Cancer Res. 1993 Dec 15;53(24):5982-6. | |||||
REF 22 | Relationships between the cytotoxicity of tiazofurin and its metabolism by cultured human lung cancer cells. J Clin Invest. 1985 Jan;75(1):175-82. | |||||
REF 23 | Antiviral agents active against influenza A viruses. Nat Rev Drug Discov. 2006 Dec;5(12):1015-25. | |||||
REF 24 | 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. | |||||
REF 25 | A potent "fat base" nucleotide inhibitor of IMP dehydrogenase. Biochemistry. 1998 Aug 25;37(34):11949-52. | |||||
REF 26 | Identification of the IMP binding site in the IMP dehydrogenase from Tritrichomonas foetus. Biochemistry. 1995 Oct 24;34(42):13889-94. | |||||
REF 27 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
REF 28 | 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. |
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