CP-724714

CP-724714 is available commercially through several vendors, and the scientific community has been using the agent largely as a cellular probe for selective and potent inhibition of HER2/ERBB2. It has an IC₅₀ of 10 nM, and is >640-fold selective against EGFR, InsR, IRG-1R, PDGFR, VEGFR2, ABL, SRC, c-MET, etc. in cell-free assays. The published information regarding the use of CP-724714 in various cell lines and in animals makes this a valuable probe for cellular assays.

If I were going to use this compound in my studies, I would also likely include Mubritinib (TAK-165), which is a potent inhibitor of HER2/ErbB2 with IC50 of 6 nM in BT-474 cells and shows no activity against EGFR, FGFR, PDGFR, JAK1, SEC or BLK in BT-474 cell lines. 

CP-724714 is a selective, cell-permeable chemical probe for ERBB2, with minimal collateral engagement to other tyrosine kinases. It has 10 nM potency with solid cellular and biophysical characterization. It has been validated in a number of cancer cell lineages, supporting its general use as a chemical probe for cellular applications. Cellular studies should be performed with >50 nM CP-724714. CP-724714 is a potent inhibitor of ERBB2 kinase in both cell-free (IC50=10 nM) and cellular (IC50=32 nM) assays with good selectivity over EGFR kinase (>500-fold) and other representative kinases (>1000-fold). Published data supports the use of CP-724714 in both cellular and mouse models at reasonable concentrations and doses. A 25 mg/kg oral dose in mouse is rapidly absorbed and achieved plasma levels of 12.5 ug/mL at 30 min.