The current toolbox for APOBEC drug discovery.
APOBEC
DNA deaminase inhibitors
chemical probes
drug discovery
screening
Journal
Trends in pharmacological sciences
ISSN: 1873-3735
Titre abrégé: Trends Pharmacol Sci
Pays: England
ID NLM: 7906158
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
08
09
2021
revised:
03
02
2022
accepted:
09
02
2022
pubmed:
12
3
2022
medline:
20
4
2022
entrez:
11
3
2022
Statut:
ppublish
Résumé
Mutational processes driving genome evolution and heterogeneity contribute to immune evasion and therapy resistance in viral infections and cancer. APOBEC3 (A3) enzymes promote such mutations by catalyzing the deamination of cytosines to uracils in single-stranded DNA. Chemical inhibition of A3 enzymes may yield an antimutation therapeutic strategy to improve the durability of current drug therapies that are prone to resistance mutations. A3 small-molecule drug discovery efforts to date have been restricted to a single high-throughput biochemical activity assay; however, the arsenal of discovery assays has significantly expanded in recent years. The assays used to study A3 enzymes are reviewed here with an eye towards their potential for small-molecule discovery efforts.
Identifiants
pubmed: 35272863
pii: S0165-6147(22)00031-1
doi: 10.1016/j.tips.2022.02.007
pmc: PMC9018551
mid: NIHMS1787010
pii:
doi:
Substances chimiques
Cytidine Deaminase
EC 3.5.4.5
Types de publication
Journal Article
Review
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
362-377Subventions
Organisme : NCI NIH HHS
ID : P01 CA234228
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI064046
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests R.S.H. and D.A.H. were cofounders of ApoGen Biotechnologies, Inc., which closed operations in April 2021. The other authors declare no conflicts of interest.
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