Discovery of novel FUT8 inhibitors with promising affinity and in vivo efficacy for colorectal cancer therapy.
Bioorg Chem
; 149: 107492, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38820939
ABSTRACT
As a member of glycosyltransferases, fucosyltransferase 8 (FUT8) is essential to core fucosylation and has been considered as a potential therapeutic target for malignant tumors, including colorectal cancer (CRC). Based on the identification of key binding residues and probable conformation of FUT8, an integrated strategy that combines virtual screening and chemical optimization was carried out and compound 15 was identified as a potent FUT8 inhibitor with novel chemical structure and in vitro antitumor activity. Moreover, chemical pulldown experiments and binding assays confirmed that compound 15 selectively bound to FUT8. In vivo, compound 15 showed promising anti-CRC effects in SW480 xenografts. These data support that compound 15 is a potential FUT8 inhibitor for CRC treatment and deserve further optimization studies.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Enzyme Inhibitors
/
Drug Discovery
/
Fucosyltransferases
/
Antineoplastic Agents
Limits:
Animals
/
Humans
Language:
En
Journal:
Bioorg Chem
/
Bioorganic chem
/
Bioorganic chemistry
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: