Emerging therapeutic opportunities for integrin inhibitors.
Nat Rev Drug Discov
; 21(1): 60-78, 2022 01.
Article
in English
| MEDLINE | ID: covidwho-2008294
ABSTRACT
Integrins are cell adhesion and signalling proteins crucial to a wide range of biological functions. Effective marketed treatments have successfully targeted integrins αIIbß3, α4ß7/α4ß1 and αLß2 for cardiovascular diseases, inflammatory bowel disease/multiple sclerosis and dry eye disease, respectively. Yet, clinical development of others, notably within the RGD-binding subfamily of αv integrins, including αvß3, have faced significant challenges in the fields of cancer, ophthalmology and osteoporosis. New inhibitors of the related integrins αvß6 and αvß1 have recently come to the fore and are being investigated clinically for the treatment of fibrotic diseases, including idiopathic pulmonary fibrosis and nonalcoholic steatohepatitis. The design of integrin drugs may now be at a turning point, with opportunities to learn from previous clinical trials, to explore new modalities and to incorporate new findings in pharmacological and structural biology. This Review intertwines research from biological, clinical and medicinal chemistry disciplines to discuss historical and current RGD-binding integrin drug discovery, with an emphasis on small-molecule inhibitors of the αv integrins.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Integrins
/
Small Molecule Libraries
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Nat Rev Drug Discov
Journal subject:
Pharmacology
/
Drug Therapy
Year:
2022
Document Type:
Article
Affiliation country:
S41573-021-00284-4
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