Biological Activity

• Target

  EGFR IC50:29pM

  IKKε IC50:1-2μM

• DescriptionMany of the tyrosine kinase enzymes which are early components of the growth signal transduction pathway in mammalian cells are encoded by proto-oncogenes, and their transformation or overexpression has been shown to occur in a large percentage of clinical cancers. The epidermal growth factor receptor (EGFR), one of the tyrosine kinase enzymes, has thus become important target for cancer therapy. PD153035 is a potent and selective inhibitor against EGFR with an IC₅₀ value of 25 pM and K_i value of 6 pM. PD153035 inhibited EGF-stimulated receptor autophosphorylation in A431 human epidermoid carcinoma cells, with IC₅₀ of 14 nM ^[3]. In cell lines with the highest level of EGFR overexpression, PD153035 concentrations of ≥ 75 nM resulted in complete inhibition of receptor autophosphorylation. PD153035 caused a dose-dependent growth inhibition of EGFR-positive cell lines, beginning at less than micromolar concentrations, and the IC₅₀ was less than 1 μM in most cases ^[4].
• MechanismPD153035 binds at the ATP site of EGFR .
• References

• [1] Bos M, Mendelsohn J, et al. PD153035, a tyrosine kinase inhibitor, prevents epidermal growth factor receptor activation and inhibits growth of cancer cells in a receptor number-dependent manner. Clin Cancer Res. 1997 Nov;3(11):2099-106.

  [2] Fry DW, Kraker AJ, et al. A specific inhibitor of the epidermal growth factor receptor tyrosine kinase. Science. 1994 Aug 19;265(5175):1093-5.

  [3] Bridges AJ, Zhou H, Cody DR, Rewcastle GW, McMichael A, Showalter HD, Fry DW, Kraker AJ, Denny WA. Tyrosine kinase inhibitors. 8. An unusually steep structure-activity relationship for analogues of 4-(3-bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a potent inhibitor of the epidermal growth factor receptor. J Med Chem. 1996 Jan 5;39(1):267-76. doi: 10.1021/jm9503613. PMID: 8568816.

  [4] Bos M, Mendelsohn J, Kim YM, Albanell J, Fry DW, Baselga J. PD153035, a tyrosine kinase inhibitor, prevents epidermal growth factor receptor activation and inhibits growth of cancer cells in a receptor number-dependent manner. Clin Cancer Res. 1997 Nov;3(11):2099-106. PMID: 9815602.