Poziotinib

Poziotinib (HM781-36B) is an irreversible pan-HER inhibitor, with IC50 values against HER1\HER2 and HER4 of 3.2\5.3 and 23.5 nM, respectively[1].

Epidermal growth factor receptors are receptor tyrosine kinases, including EGFR/HER1\HER2/ErbB2\HER3/ErbB3 and HER4/ErbB4, and play important roles in cell proliferation and differentiation. The EGFR family is a major target of anticancer drugs[1].

Poziotinib is an irreversible pan-HER inhibitor. In HER2-amplified gastric cancer cells SNU216 and N87, HM781-36B inhibits cell growth, with IC50 values of 4 and 1 nM, respectively. In addition, HM781-36B effectively inhibits phosphorylation of the HER family and downstream proteins such as STAT3\AKT and ERK, and induces G1 arrest and apoptosis. HM781-36B increases, in a dose-dependent manner, the levels of effector caspases (caspase-3 and caspase-7) and cleaved PARP, decreases the anti-apoptotic proteins BCL-2 and MCL-1, and induces the pro-apoptotic protein BIM[1]. In HER2-amplified breast cancer cells, HM781-36B inhibits the growth of SK-BR-3\BT474 and MDA-MB-453 cells, with IC50 values of 1\1.2 and 9.5 nM, respectively[2].

In an N87 human gastric cancer xenograft nude mouse model, HM781-36B significantly inhibits tumor growth and shows a synergistic effect when administered with chemotherapeutic agents[1].

References:
[1].? Nam HJ, Kim HP, Yoon YK, et al. Antitumor activity of HM781-36B, an irreversible Pan-HER inhibitor, alone or in combination with cytotoxic chemotherapeutic agents in gastric cancer. Cancer Lett, 2011, 302(2): 155-165.
[2].? Kim HJ, Kim HP, Yoon YK, et al. Antitumor activity of HM781-36B, a pan-HER tyrosine kinase inhibitor, in HER2-amplified breast cancer cells. Anticancer Drugs, 2012, 23(3): 288-297.