isocitrate dehydrogenase (NADP(+)) 1, cytosolic | 1.1.1.42 Isocitrate dehydrogenases | IUPHAR/BPS Guide to PHARMACOLOGY

isocitrate dehydrogenase (NADP(+)) 1, cytosolic

Target id: 2884

Nomenclature: isocitrate dehydrogenase (NADP(+)) 1, cytosolic

Systematic Nomenclature: IDH1

Family: 1.1.1.42 Isocitrate dehydrogenases

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for isocitrate dehydrogenase (NADP(+)) 1, cytosolic in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 414 2q33.3 IDH1 isocitrate dehydrogenase (NADP(+)) 1, cytosolic
Mouse - 414 1 C2 Idh1 isocitrate dehydrogenase 1 (NADP+), soluble
Rat - 414 9q32 Idh1 isocitrate dehydrogenase (NADP(+)) 1, cytosolic
Previous and Unofficial Names
isocitrate dehydrogenase 1 (NADP+), soluble | isocitrate dehydrogenase [NADP] cytoplasmic | isocitrate dehydrogenase 1 (NADP) | isocitrate dehydrogenase 1 (NADP+) | isocitrate dehydrogenase (NADP(+)) 1
Database Links
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 1.1.1.42 Isocitrate + NADP(+) <=> 2-oxoglutarate + CO2 + NADPH
Description Reaction Reference
Isocitrate + NADP+ <=> 2-oxoglutarate + CO2 + NADPH

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
AGI-5198 Hs Inhibition 4.9 pKi
pKi 4.9 (Ki 1.3x10-5 M)
ivosidenib Hs Inhibition - - 2
[2]
Inhibitor Comments
The two ligands curated against this target are highly selective for mutant IDH1 isoforms and have low activity against wild type enzyme.
Clinically-Relevant Mutations and Pathophysiology
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human R132C, R132G, R132S, R132H, R132L 394C>T, 394C>G, 394C>A, 395G>A, 395G>T IDH1 mutations associated with cancers such as glioma and some hematological malignancies. 6,8
Clinically-Relevant Mutations and Pathophysiology Comments
The majority (80-90%) of IDH1 mutations in glioma are R132H. IDH1 is mutated in the majority of lower grade diffuse gliomas (grades II-III) and also in most secondary glioblastomas. It is rare in newly diagnosed glioblastoma.

References

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1. DiNardo CD, Stein EM, de Botton S, Roboz GJ, Altman JK, Mims AS, Swords R, Collins RH, Mannis GN, Pollyea DA et al.. (2018) Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML. N. Engl. J. Med., 378 (25): 2386-2398. [PMID:29860938]

2. Lemieux RM, Popovici-Muller J, Travins J, Cai Z, Cui D, Zhou D. (2013) Therapeutically active compounds and their methods of use. Patent number: WO2013107291. Assignee: Agios Pharmaceuticals, Inc.. Priority date: 19/01/2012. Publication date: 25/07/2013.

3. Linos K, Tafe LJ. (2018) Isocitrate Dehydrogenase 1 (IDH1) Mutations in Melanoma Frequently Co-Occur with NRAS Mutations. Histopathology, [Epub ahead of print]. [PMID:30003571]

4. Ma T, Zou F, Pusch S, Xu Y, von Deimling A, Zha X. (2018) Inhibitors of Mutant Isocitrate Dehydrogenases 1 and 2 (mIDH1/2): An Update and Perspective. J. Med. Chem., [Epub ahead of print]. [PMID:29847930]

5. Morizane C, Ueno M, Ikeda M, Okusaka T, Ishii H, Furuse J. (2018) New developments in systemic therapy for advanced biliary tract cancer. Jpn. J. Clin. Oncol., 48 (8): 703-711. [PMID:29893894]

6. Rohle D, Popovici-Muller J, Palaskas N, Turcan S, Grommes C, Campos C, Tsoi J, Clark O, Oldrini B, Komisopoulou E et al.. (2013) An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science, 340 (6132): 626-30. [PMID:23558169]

7. Sidaway P. (2018) Ivosidenib effective in IDH1-mutant AML. Nat Rev Clin Oncol, 15 (8): 472. [PMID:29925981]

8. Walter MJ, Shen D, Shao J, Ding L, White BS, Kandoth C, Miller CA, Niu B, McLellan MD, Dees ND et al.. (2013) Clonal diversity of recurrently mutated genes in myelodysplastic syndromes. Leukemia, 27 (6): 1275-82. [PMID:23443460]

9. Zhao Q, Manning JR, Sutton J, Costales A, Sendzik M, Shafer CM, Levell JR, Liu G, Caferro T, Cho YS et al.. (2018) Optimization of 3-Pyrimidin-4-yl-oxazolidin-2-ones as Orally Bioavailable and Brain Penetrant Mutant IDH1 Inhibitors. ACS Med Chem Lett, 9 (7): 746-751. [PMID:30034612]

How to cite this page

1.1.1.42 Isocitrate dehydrogenases: isocitrate dehydrogenase (NADP(+)) 1, cytosolic. Last modified on 30/07/2018. Accessed on 21/09/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2884.