Structural studies of full-length receptor tyrosine kinases and their implications for drug design.
Drug design
EGFR
Kinase inhibitors
Kinases
Kit
PDGFR
Receptor kinases
Structural biology
Tyrosine kinases
Journal
Advances in protein chemistry and structural biology
ISSN: 1876-1631
Titre abrégé: Adv Protein Chem Struct Biol
Pays: Netherlands
ID NLM: 101497281
Informations de publication
Date de publication:
2021
2021
Historique:
entrez:
26
2
2021
pubmed:
27
2
2021
medline:
6
5
2021
Statut:
ppublish
Résumé
Receptor tyrosine kinases (RTKs) are important drug targets for cancer and immunological disorders. Crystal structures of individual RTK domains have contributed greatly to the structure-based drug design of clinically used drugs. Low-resolution structures from electron microscopy are now available for the RTKs, EGFR, PDGFR, and Kit. However, there are still no high-resolution structures of full-length RTKs due to the technical challenges of working with these complex, membrane proteins. Here, we review what has been learned from structural studies of these three RTKs regarding their mechanisms of ligand binding, activation, oligomerization, and inhibition. We discuss the implications for drug design. More structural data on full-length RTKs may facilitate the discovery of druggable sites and drugs with improved specificity and effectiveness against resistant mutants.
Identifiants
pubmed: 33632469
pii: S1876-1623(20)30085-7
doi: 10.1016/bs.apcsb.2020.10.007
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Neoplasm Proteins
0
Protein Kinase Inhibitors
0
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
311-336Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.