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Small-molecule ATP-competitive dual IGF-1R and insulin receptor inhibitors: structural insights, chemical diversity and molecular evolution
- Source :
- Future Medicinal Chemistry. 4:315-328
- Publication Year :
- 2012
- Publisher :
- Future Science Ltd, 2012.
-
Abstract
- IGF-1R has been recognized as a major target in cancer drug discovery due to its strong implications in various stages of tumorigenesis based on accumulated preclinical data. Recent research on compensatory crosstalk between IGF-1R and insulin receptor (IR) signaling pathways suggests that targeting both IGF-1R and IR should result in a more therapeutically beneficial response, than targeting IGF-1R alone (e.g., IGF-1R-specific antibodies). These findings provided biological rationale and opened the door to the discovery of a variety of small-molecule dual IGF-1R and IR inhibitors. In this review we summarize the recent developments in this field, with a focus on binding modes and binding interactions of these inhibitors with IGF-1R and/or IR. Selectivity of these inhibitors has been discussed in this context as well. This is an important area to be discussed since one of the major challenges in kinase inhibitor drug discovery is to build an optimal selectivity profile based on biological rationale.
- Subjects :
- Models, Molecular
Antineoplastic Agents
Computational biology
Biology
Pharmacology
medicine.disease_cause
Receptor, IGF Type 1
Small Molecule Libraries
Adenosine Triphosphate
Neoplasms
Drug Discovery
medicine
Animals
Humans
Receptor
Protein Kinase Inhibitors
Drug discovery
Kinase
Small molecule
Receptor, Insulin
Crosstalk (biology)
Insulin receptor
biology.protein
Molecular Medicine
Signal transduction
Carcinogenesis
Subjects
Details
- ISSN :
- 17568927 and 17568919
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- Future Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....4e916e901e50f5254653375e12624414