Insulin-Like Growth Factor System in Cancer: Novel Targeted Therapies

Table 5

Few examples of small molecule TKIs (tyrosine kinase inhibitors) directed against IGF receptors.

Small molecule inhibitor	Mode of action	Effects	Reference
NVP-AEW541; NVP-AEW54 in combination with gemcitabine	Kinase inhibition	Antineoplastic, tumour regression and inhibition of metastasis	[216, 217]
Picropodophyllin (PPP)	Against autophosphorylation at the substrate level	Inhibition and downregulation of IGF-1R	[218–221]
BMS-554417	ATP-competitive, dual kinase inhibition	Antiproliferative activity	[222]
INSM-18	Reversible; ATP-competitive	Inhibitor of transcription (blocking also cdc2, survivin, and VEGF)	[223]
OSI-906	Reversible; ATP-competitive	Derived from compound-1, also known as PQIP	[223]
XL-228 (XL-2280)		Inhibits bcr-abl, scr, and IGF-1R	[224]
BVP-51004 Biovitrum (Cyclolignan PPP)	Non-ATP-competitive	Causes IGF-1R downregulation, probably through the induction of ubiquitination.	[223]