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inosine monophosphate dehydrogenase 2

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Target not currently curated in GtoImmuPdb

Target id: 2625

Nomenclature: inosine monophosphate dehydrogenase 2

Abbreviated Name: IMPDH2

Family: Nucleoside synthesis and metabolism, 1.-.-.- Oxidoreductases

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 514 3p21.31 IMPDH2 inosine monophosphate dehydrogenase 2
Mouse - 514 9 F2 Impdh2 inosine monophosphate dehydrogenase 2
Rat - 514 8q32 Impdh2 inosine monophosphate dehydrogenase 2
Previous and Unofficial Names Click here for help
IMP (inosine 5'-monophosphate) dehydrogenase 2 | inosine 5'-phosphate dehydrogenase 2
Database Links Click here for help
Alphafold P12268 (Hs), P24547 (Mm), E9PU28 (Rn)
BRENDA 1.1.1.205
CATH/Gene3D 3.20.20.70
ChEMBL Target CHEMBL2002 (Hs), CHEMBL3169 (Mm)
DrugBank Target P12268 (Hs)
Ensembl Gene ENSG00000178035 (Hs), ENSMUSG00000062867 (Mm), ENSRNOG00000031965 (Rn)
Entrez Gene 3615 (Hs), 23918 (Mm), 301005 (Rn)
Human Protein Atlas ENSG00000178035 (Hs)
KEGG Enzyme 1.1.1.205
KEGG Gene hsa:3615 (Hs), mmu:23918 (Mm), rno:301005 (Rn)
OMIM 146691 (Hs)
Pharos P12268 (Hs)
RefSeq Nucleotide NM_000884 (Hs), NM_011830 (Mm), NM_199099 (Rn)
RefSeq Protein NP_000875 (Hs), NP_035960 (Mm), NP_954530 (Rn)
UniProtKB P12268 (Hs), P24547 (Mm), E9PU28 (Rn)
Wikipedia IMPDH2 (Hs)
Enzyme Reaction Click here for help
EC Number: 1.1.1.205

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
merimepodib Small molecule or natural product Hs Inhibition 8.0 pIC50 1
⤷ pIC50 8.0 (IC50 1x10-8 M) [1]
mycophenolic acid Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pIC50 4
⤷ pIC50 7.7 (IC50 2x10-8 M) [4]
Description: Reference does not distinguish which enzyme isoform is assayed
ribavirin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.6 – 6.0 pIC50 8
⤷ pIC50 5.6 – 6.0 (IC50 2.5x10-6 – 1x10-6 M) [8]
Description: In vitro inhibition of IMPDH (isoform not specified, human and mouse assayed)
mycophenolate mofetil Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition - -
⤷ See Inhibitor Comment below
thioguanine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition - - 2,7
⤷ [2,7]
Inhibitor Comments
In general there is little evidence identifying any isoform specificity in the action of the IMPDH inhibitors.
Further information regarding the use and effectiveness of mycophenolate mofetil is contained in these references:- [5-6].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Cellular signalling
Immuno Process:  Cytokine production & signalling
General Comments
SARS-CoV-2/COVID-19
Experimental in vitro evidence, using affinity-purification mass spectrometry (AP-MS), indicates a protein-protein interaction between IMPDH2 and the SARS-CoV-2 non-structural protein 14 (Nsp14) [3], although whether this interaction is realistic based on spatial distribution of the host and viral proteins within cells was not addressed in this study. Speculatively, IMPDH inhibitors such as mycophenolic acid and merimepodib could be utilised to examine the effect of inhibiting the IMPDH2/Nsp14 protein-protein interaction on SARS-CoV-2 pathobiology.

References

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1. Dhar TG, Shen Z, Guo J, Liu C, Watterson SH, Gu HH, Pitts WJ, Fleener CA, Rouleau KA, Sherbina NZ et al.. (2002) Discovery of N-[2-[2-[[3-methoxy-4-(5-oxazolyl)phenyl]amino]-5-oxazolyl]phenyl]-N-methyl-4- morpholineacetamide as a novel and potent inhibitor of inosine monophosphate dehydrogenase with excellent in vivo activity. J Med Chem, 45 (11): 2127-30. [PMID:12014950]

2. Elgemeie GH. (2003) Thioguanine, mercaptopurine: their analogs and nucleosides as antimetabolites. Curr Pharm Des, 9 (31): 2627-42. [PMID:14529546]

3. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL et al.. (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature, 583 (7816): 459-468. [PMID:32353859]

4. Nelson PH, Eugui E, Wang CC, Allison AC. (1990) Synthesis and immunosuppressive activity of some side-chain variants of mycophenolic acid. J Med Chem, 33 (2): 833-8. [PMID:1967654]

5. Sanquer S, Maison P, Tomkiewicz C, Macquin-Mavier I, Legendre C, Barouki R, Lang P. (2008) Expression of inosine monophosphate dehydrogenase type I and type II after mycophenolate mofetil treatment: a 2-year follow-up in kidney transplantation. Clin Pharmacol Ther, 83 (2): 328-35. [PMID:17713475]

6. Sollinger HW. (1996) From mice to man: the preclinical history of mycophenolate mofetil. Clin Transplant, 10 (1 Pt 2): 85-92. [PMID:8680054]

7. Vethe NT, Bremer S, Bergan S. (2008) IMP dehydrogenase basal activity in MOLT-4 human leukaemia cells is altered by mycophenolic acid and 6-thioguanosine. Scand J Clin Lab Invest, 68 (4): 277-85. [PMID:18609073]

8. Wittine K, Stipković Babić M, Makuc D, Plavec J, Kraljević Pavelić S, Sedić M, Pavelić K, Leyssen P, Neyts J, Balzarini J et al.. (2012) Novel 1,2,4-triazole and imidazole derivatives of L-ascorbic and imino-ascorbic acid: synthesis, anti-HCV and antitumor activity evaluations. Bioorg Med Chem, 20 (11): 3675-85. [PMID:22555152]

How to cite this page

Nucleoside synthesis and metabolism: inosine monophosphate dehydrogenase 2. Last modified on 03/04/2020. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2625.