acyl-CoA synthetase short chain family member 2 | Acyl-CoA synthetases | IUPHAR/BPS Guide to PHARMACOLOGY

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acyl-CoA synthetase short chain family member 2

Target not currently curated in GtoImmuPdb

Target id: 3128

Nomenclature: acyl-CoA synthetase short chain family member 2

Family: Acyl-CoA synthetases

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

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 701 20q11.22 ACSS2 acyl-CoA synthetase short chain family member 2
Gene and Protein Information Comments
Alternative splicing results in multiple transcript variants and isozymes.
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
example 265 [WO2019097515A1] Hs Inhibition 8.4 pIC50 4
pIC50 8.4 (IC50 4.5x10-9 M) [4]
Description: Measuring in vitro inhibition of ACSS2-mediated Fatty-acid synthesis in MDA-MB-468 cells under hypoxic conditions.
ADG-207 Mm Inhibition - - 3
[3]
Description: As determined from in vivo exposure in mice.
View species-specific inhibitor tables
General Comments
Acyl-CoA synthetase short chain family member 2 (ACSS2) is a monomeric cytosolic enzyme that catalyses the activation of acetate for use in lipid synthesis and energy generation. Cellular stress induced by oxygen or glucose deprivation increases intracellular acetate levels. Under these conditions ACSS2 translocates to the nucleus where it promotes acetylation of the stress-responsive hypoxia Inducible factor 2αα and increases histone H3K27 acetylation [1]. The acetate/ACSS2/histone acetylation influence on epithelial-mesenchymal transition (EMT) and cancer cell metastasis is being investigated [5], and ACSS2 inhibitor development is underway [2,4].

References

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1. Chen R, Xu M, Nagati J, Garcia JA. (2017) Coordinate regulation of stress signaling and epigenetic events by Acss2 and HIF-2 in cancer cells. PLoS ONE, 12 (12): e0190241. [PMID:29281714]

2. Kargbo RB. (2019) Inhibition of ACSS2 for Treatment of Cancer and Neuropsychiatric Diseases. ACS Med Chem Lett, 10 (8): 1100-1101. [PMID:31413791]

3. Mews P, Berger Sl, Winkler JD, Glass A. (2019) Compositions and methods for inhibiting acss2. Patent number: WO2019067528A1. Assignee: The Trustees Of The University Of Pennsylvania. Priority date: 26/09/2017. Publication date: 04/04/2019.

4. Nakache P, Erez O, Botti S, Goutopoulos A, Labelle M. (2019) Acss2 inhibitors and methods of use thereof. Patent number: WO2019097515A1. Assignee: Metabomed Ltd. Priority date: 15/11/2017. Publication date: 23/05/2019.

5. Yao L, Jiang L, Zhang F, Li M, Yang B, Zhang F, Guo X. (2020) Acetate promotes SNAI1 expression by ACSS2-mediated histone acetylation under glucose limitation in renal cell carcinoma cell. Biosci. Rep., 40 (6). DOI: 10.1042/BSR20200382 [PMID:32458971]

How to cite this page

Acyl-CoA synthetases: acyl-CoA synthetase short chain family member 2. Last modified on 18/06/2020. Accessed on 10/07/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3128.