生物活性

• 靶点

  EGFR IC50:3nM

  ERBB4 IC50:23nM

  HER2 IC50:5nM

• 描述EGFR (epidermal growth factor receptor) family consists of four members that belong to the ErbB lineage of proteins (ErbB1 - 4) with an external domain that binds activating ligands, such as EGF, and is overexpressed in a significant percentage of carcinomas and contributes to the malignant phenotype. Poziotinib is an irreversible pan-ErbB inhibitor with IC50 values of 3.2 nM, 5.3 nM and 23.5 nM for ErbB1, ErbB2 and ErbB4 (measured by in vitro kinase assays), respectively. Compared to other HER family TKIs like Lapatinib, Cl-1033, Gefitinib and BIBW-2992, Poziotinib has potent growth inhibitory activity against ErbB2 amplified gastric cancer cells, including SNU-1, 5, 16, 216, 484, 601, 620, 638, 668, 719, N87 and AGS, along with more potent inhibition on the phosphorylation of HER family and the key components of downstream signaling cascades such as STAT3, AKT and ERK, and also induces G1 cell cycle arrest and apoptosis with activation on the mitochondrial pathway. In vivo study showed that Poziotinib (0.5 mg/kg) exerted a synergistic effect with 5-FU (50 mg/kg) in a nude mouse bearing N87 human gastric cancer xenograft model^[1].
• 作用机制Poziotinib can covalently bind and inhibit mutant EGFR and HER2 kinases^[2].

• 动物研究
  剂量	Mice: 0.3 mg/kg21732342 (p.o.)
  给药途径	p.o.
  动物药代数据	Animal Dogs[3] Dose 0.3 mg/kg Administration p.o. Cmax 321.2 ± 51.8 ng/ml T1/2 4.4 ± 1.0 h AUClast 1712.5 ± 835.6 ng·h/ml Tmax 0.7 ± 0.3 h

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03292250	HNSCC Head an... more >>d Neck Neoplasms Collapse <<	Phase 2	Recruiting	December 31, 2020	Korea, Republic of ... more >> Seoul National University Hospital Recruiting Seoul, Korea, Republic of, 110-744 Contact: Bhumsuk Keam, MD    82-2-2072-7215    bhumsuk@snu.ac.kr    Principal Investigator: Hye Ryun Kim          Principal Investigator: Hwan Jung Yun          Principal Investigator: Myung-Ju Ahn          Principal Investigator: Sung Bae Kim          Principal Investigator: Hyun Chang          Principal Investigator: Sang Hoon Chun          Principal Investigator: InSook Woo          Principal Investigator: Yoon Ho Ko          Principal Investigator: Ji Hyung Hong          Principal Investigator: jung hye kwon          Principal Investigator: Heui-june Ahn          Principal Investigator: Yun Gyoo Lee          Principal Investigator: Keonuk Park          Principal Investigator: Eun Joo Kang          Principal Investigator: Seong-Hoon Shin          Principal Investigator: Tak Yun          Principal Investigator: Yoon Hee Choi          Principal Investigator: Keun-Wook Lee          Principal Investigator: Joo-Hang Kim          Principal Investigator: JinSoo Kim          Principal Investigator: Sang-Cheol Lee          Principal Investigator: Hyun Woo Lee          Principal Investigator: Min Kyoung Kim          Principal Investigator: Hyeok Shim          Principal Investigator: Seung taek Lim          Principal Investigator: Kyoung Eun Lee          Principal Investigator: Moon Young Choi          Principal Investigator: Joohan Lim          Principal Investigator: In Gyu Hwang          Principal Investigator: Hyo Jung Kim          Principal Investigator: Jun Eul Hwang          Principal Investigator: Ho Jung An          Principal Investigator: So Yeon Oh          Principal Investigator: Sang-Gon Park          Principal Investigator: Hee Kyoung Ahn          Principal Investigator: Sun Min Lim Collapse <<
  NCT01455571	Advanced Solid Tumor	Phase 1	Completed	-	Korea, Republic of ... more >> Seoul National University Hospital Seoul, Korea, Republic of Collapse <<
  NCT02216916	HNSCC	Phase 2	Unknown	August 2016	Korea, Republic of ... more >> Yonsei University Recruiting Seoul, Korea, Republic of Contact: Cho Byung Chul    82-10-5212-8867 ext 84320    cbc1971@yuhs.ac Collapse <<

• 更多
• 参考文献

• [1] Nam HJ, Kim HP, 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 Mar 28;302(2):155-65.

  [2] Cha MY, Lee KO, et al. Antitumor activity of HM781-36B, a highly effective pan-HER inhibitor in erlotinib-resistant NSCLC and other EGFR-dependent cancer models. Int J Cancer. 2012 May 15;130(10):2445-54.

  [3] Kim E, Kim H, et al. Metabolite identification of a new tyrosine kinase inhibitor, HM781-36B, and a pharmacokinetic study by liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 2013 Jun 15;27(11):1183-95.