tcsc0142 PD153035 (Hydrochloride)

PD153035 (ZM 252868; AG 1517; SU 5271) is a potent EGFR inhibitor with K_i and IC₅₀ of 6 and 25 pM, respectively.

IC50 & Target: IC50: 25 pM (EGFR)^[1]

Ki: 6 pM (EGFR)^[1]

In Vitro: PD153035 inhibits EGF-stimulated receptor autophosphorylation in A431 human epidermoid carcinoma cells, with an IC₅₀ of 14 nM^[1]. PD 153035 has little effect on PDGFR, FGFR, CSF-1 receptor, the insulin receptor, or on src tyrosine kinases at concentrations as high as 50 μM. PD 153035 rapidly suppresses autophosphorylation of the EGF receptor at low nanomolar concentrations in fibroblasts or in human epidermoid carcinoma cells and selectively blocks EGF-mediated cellular processes including mitogenesis, early gene expression, and oncogenic transformation^[2]. PD153035 causes a dose-dependent growth inhibition of EGF receptor-positive cell lines, beginning at less than micromolar concentrations, and the IC₅₀ is less than 1 pM in most cases^[3].

In Vivo: PD153035 levels in the plasma and tumor rise to 50 and 22 μM within 15 minutes following a single i.p. dose of 80 mg/kg. While the plasma levels of PD 153035 falls below 1 μM by 3 hours, in the tumors it remains at micromolar concentrations for at least 12 hours. The tyrosine phosphorylation of the EGF receptor is rapidly suppressed by 80-90% in the tumors^[4].