Novel mutant-selective EGFR kinase inhibitors against EGFR T790M

Wenjun Zhou, Dalia Ercan, Liang Chen, Cai-Hong Yun, Danan Li, Marzia Capelletti, Alexis B. Cortot, Lucian Chirieac, Roxana E. Iacob, Robert Padera, John R. Engen, Kwok-Kin Wong, Michael J. Eck, Nathanael S. Gray () and Pasi A. Jänne ()
Additional contact information
Wenjun Zhou: Department of Cancer Biology,
Dalia Ercan: Lowe Center for Thoracic Oncology,
Liang Chen: Lowe Center for Thoracic Oncology,
Cai-Hong Yun: Department of Cancer Biology,
Danan Li: Lowe Center for Thoracic Oncology,
Marzia Capelletti: Lowe Center for Thoracic Oncology,
Alexis B. Cortot: Lowe Center for Thoracic Oncology,
Lucian Chirieac: Brigham and Women’s Hospital, Boston, Massachusetts 02115, USA
Roxana E. Iacob: The Barnett Institute of Chemical & Biological Analysis,
Robert Padera: Brigham and Women’s Hospital, Boston, Massachusetts 02115, USA
John R. Engen: The Barnett Institute of Chemical & Biological Analysis,
Kwok-Kin Wong: Lowe Center for Thoracic Oncology,
Michael J. Eck: Department of Cancer Biology,
Nathanael S. Gray: Department of Cancer Biology,
Pasi A. Jänne: Lowe Center for Thoracic Oncology,

Nature, 2009, vol. 462, issue 7276, 1070-1074

Abstract: Antitumour drugs: novel EGFR inhibitors Non-small-cell lung tumours with activating mutations in the epidermal growth factor receptor (EGFR) often show a clinical response to receptor inhibitors, but tend to develop resistance due to the additional EGFR T790M mutations. Pasi Jänne and colleagues now have developed a new class of EGFR inhibitor that selectively inhibits the mutant receptor, rather that the wild type, and also inhibits the T790M mutant. These compounds reduce tumour growth in a mouse model and may prove more clinically effective and better tolerated than current EGFR kinase inhibitors in clinical use.

Date: 2009
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DOI: 10.1038/nature08622

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