Protein Function Inhibitors / ApproachesDRUGS THAT TARGET ALTERED PROTEIN FUNCTION
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A significant spectrum of action exists among protein function inhibitors. At one end are drugs that target a unique aspect of a specific cancer type (such as L-ASPARAGINASE and IMATINIB); less specific are those that block growth factors or their receptors (such as ERLOTINIB and GEFITINIB); and at the other end are drugs that are really targeting rapidly dividing cells and/or angiogenesis (like BORTEZOMIB, VORINOSTAT, SORAFENIB and SUNITINIB). |
- development of drugs that target proteins that are mutated or overexpressed in cancer cells (especially tyrosine kinases) is an extremely active research area, and there are many "NIBs" in clinical trials
- this concept is an important aspect of personalized medicine
Targets
I. Tyrosine kinases:
- Bcr-Abl: BOSUTINIB, DASATINIB, IMATINIB, NILOTINIB
- EGFR: CETUXIMAB, ERLOTINIB, GEFITINIB, PANITUMUMAB
- HER2: PERTUZUMAB, TRASTUZUMAB [ADO-TRASTUZUMAB EMTANSINE]
- PDGF-R, VEGF-R: PAZOPANIB, SORAFENIB, SUNITINIB (discussed under angiogenesis inhibitors)
II. Altered intracellular processes
- Deplete asparagine: L-ASPARAGINASE
- Proteosome: BORTEZOMIB, CARFILZOMIB
- HDAC: ROMIDEPSIN, VORINOSTAT
- Promyelocytic protein: ARSENIC TRIOXIDE (ATO), BEXAROTENE, TRETINOIN (discussed under differentiating agents)
N.B. The signal transduction inhibitors that target Bcr-Abl and EGFR will be presented in lecture V not lecture IV, but on this website they are kept in this mechanistic class
- in other words, the "lecture" series and this website will handle these drugs a little bit differently