Targeting MYC: From understanding its biology to drug discovery.
Eur J Med Chem
; 213: 113137, 2021 Mar 05.
Article
in En
| MEDLINE
| ID: mdl-33460833
ABSTRACT
The MYC oncogene is considered to be a high priority target for clinical intervention in cancer patients due to its aberrant activation in more than 50% of human cancers. Direct small molecule inhibition of MYC has traditionally been hampered by its intrinsically disordered nature and lack of both binding site and enzymatic activity. In recent years, however, a number of strategies for indirectly targeting MYC have emerged, guided by the advent of protein structural information and the growing set of computational tools that can be used to accelerate the hit to lead process in medicinal chemistry. In this review, we provide an overview of small molecules developed for clinical applications of these strategies, which include stabilization of the MYC guanine quadruplex, inhibition of BET factor BRD4, and disruption of the MYCMAX heterodimer. The recent identification of novel targets for indirect MYC inhibition at the protein level is also discussed.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proto-Oncogene Proteins c-myc
/
Small Molecule Libraries
/
Drug Discovery
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Eur J Med Chem
Year:
2021
Document type:
Article
Affiliation country:
Canada