The discovery of lapatinib (GW572016).
نویسندگان
چکیده
Commentary on: David W. Rusnak, Karen Lackey, Karen Affleck, Edgar R. Wood, Krystal J. Alligood, Nelson Rhodes, Barry R. Keith, DorisM.Murray,W. BlaineKnight, Robert J.Mullin, and Tona M. Gilmer. The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumorderived cell lines in vitro and in vivo. Mol Cancer Ther 2001;1:85–94.
منابع مشابه
A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells.
GW572016 (Lapatinib) is a tyrosine kinase inhibitor in clinical development for cancer that is a potent dual inhibitor of epidermal growth factor receptor (EGFR, ErbB-1) and ErbB-2. We determined the crystal structure of EGFR bound to GW572016. The compound is bound to an inactive-like conformation of EGFR that is very different from the active-like structure bound by the selective EGFR inhibit...
متن کاملPhase I dose-escalation and pharmacokinetic trial of lapatinib (GW572016), a selective oral dual inhibitor of ErbB-1 and -2 tyrosine kinases, in Japanese patients with solid tumors.
OBJECTIVE The Phase I dose-escalation study was conducted to evaluate the safety and pharmacokinetics of lapatinib (GW572016), a dual ErbB-1 and -2 inhibitor, in Japanese patients with solid tumors that generally express ErbB-1 and/or overexpress ErbB-2. METHODS Patients received oral lapatinib once daily until disease progression or in an event of unacceptable toxicity. RESULTS Twenty-four...
متن کاملAntitumor effects of lapatinib (GW572016), a dual inhibitor of EGFR and HER-2, in combination with cisplatin or paclitaxel on head and neck squamous cell carcinoma.
The epidermal growth factor receptor (EGFR) and a related family member, HER-2, are often overexpressed simultaneously in patients with a variety of malignant tumors, and the combination may cooperatively promote cancer cell growth and survival. Heterodimerization of EGFR and HER-2 has been known to create intense proliferative signals. Lapatinib (GW572016) is a small molecule that is administr...
متن کاملThe role of efflux and uptake transporters in [N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine (GW572016, lapatinib) disposition and drug interactions.
Lapatinib [N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine, GW572016, Tykerb] is a tyrosine kinase inhibitor approved for use in combination with capecitabine to treat advanced or metastatic breast cancers overexpressing HER2 (ErbB2). In this work we investigated the role of efflux and uptake transporters in lapatinib dispositi...
متن کاملActivity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells.
Lapatinib (GW572016) is a selective inhibitor of both epidermal growth factor receptor (EGFR) and HER-2 tyrosine kinases. Here, we explore the therapeutic potential of lapatinib by testing its effect on tumor cell growth in a panel of 31 characterized human breast cancer cell lines, including trastuzumab-conditioned HER-2-positive cell lines. We further characterize its activity in combination ...
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عنوان ژورنال:
- Molecular cancer therapeutics
دوره 10 11 شماره
صفحات -
تاریخ انتشار 2011