Medicinal chemistry approaches to target the kinase activity of IGF-1R.
Various drug discovery approaches have been explored in recent years to modulate the function of insulin-like growth factor-1 receptor (IGF-1R). This article focuses on the contributions of low-molecular-mass inhibitors in the modulation of IGF-1R kinase activity, and provides an update on recent reviews for this type of agent. Different classes of compounds have been demonstrated to be capable of modulating the kinase activity of IGF-1R in ways that were not possible previously. Preclinical data with some of these inhibitors support the potential application of IGF-1R-targeted therapeutic strategies in the treatment of human cancers.
Garcia-Echeverria
Carlos
C
Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH-4002 Basel, Switzerland. carlos.garcia-echeverria@novartis.com
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000201:enzymology; D011034:Podophyllotoxin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D011485:Protein Binding; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011728:Pyridones / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D020032:Tyrphostins / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; C504983:BMS 536924; D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D011728:Pyridones; D011743:Pyrimidines; D011758:Pyrroles; D020032:Tyrphostins; C447031:tyrphostin AG 1024; C415032:picropodophyllin; D000255:Adenosine Triphosphate; D017526:Receptor, IGF Type 1; D011034:Podophyllotoxin; C502355:NVP ADW742