Title:
INHIBITOR OR DOWN- REGULATOR OF THE EXPRESSION OF ONE OR BOTH OF TBK1 IKK-EPSILON FOR USE IN THE TREATMENT OF PI3KINASE DEPENDENT CANCER
Document Type and Number:
WIPO Patent Application WO/2013/024282
Kind Code:
A3
Abstract:
The invention provides a compound that is an inhibitor of one or both of TBK1 and IKKε, or a down-regulator of the expression of one or both of TBK1 and IKKε, for use in a method of treating a cancer that is dependent on the PI3kinase pathway. The invention further provides a method of treating cancer in an individual in whom the cancer is dependent on the PI3kinase pathway, comprising administering to the individual a compound that is an inhibitor of one or both of TBK1 and IKKε, or a down-regulator of the expression of one or both of TBK1 and IKKε.
Inventors:
NEWTON GARY (GB)
PERRIOR TREVOR (GB)
ASHWORTH ALAN (GB)
LORD CHRISTOPHER JAMES (GB)
PERRIOR TREVOR (GB)
ASHWORTH ALAN (GB)
LORD CHRISTOPHER JAMES (GB)
Application Number:
PCT/GB2012/051978
Publication Date:
May 16, 2013
Filing Date:
August 14, 2012
Export Citation:
Assignee:
DOMAINEX LTD (GB)
NEWTON GARY (GB)
PERRIOR TREVOR (GB)
ASHWORTH ALAN (GB)
LORD CHRISTOPHER JAMES (GB)
NEWTON GARY (GB)
PERRIOR TREVOR (GB)
ASHWORTH ALAN (GB)
LORD CHRISTOPHER JAMES (GB)
International Classes:
A61K31/506; A61K31/404; A61K31/4184; A61K31/427; A61K31/437; A61K31/519; A61P35/00
Domestic Patent References:
| WO2005034978A2 | 2005-04-21 | |||
| WO2011046970A1 | 2011-04-21 | |||
| WO2009030890A1 | 2009-03-12 | |||
| WO2009122180A1 | 2009-10-08 | |||
| WO2010100431A1 | 2010-09-10 | |||
| WO2012010826A1 | 2012-01-26 | |||
| WO2009103790A2 | 2009-08-27 |
Foreign References:
| US20070149469A1 | 2007-06-28 |
Other References:
YI-HUNG OU ET AL: "TBK1 Directly Engages Akt/PKB Survival Signaling to Support Oncogenic Transformation", MOLECULAR CELL, CELL PRESS, CAMBRIDGE, MA, US, vol. 41, no. 4, 24 December 2010 (2010-12-24), pages 458 - 470, XP028169620, ISSN: 1097-2765, [retrieved on 20110129], DOI: 10.1016/J.MOLCEL.2011.01.019
SERVANT, M.J. ET AL.: "The IKK-related kinases, unsuspected culprits in oncogenesis?", March 2009 (2009-03-01), XP002685965, Retrieved from the Internet [retrieved on 20121024]
XIE XIAODUO ET AL: "IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 19 APR 2011 LNKD- PUBMED:21464307, vol. 108, no. 16, 19 April 2011 (2011-04-19), pages 6474 - 6479, XP002685966, ISSN: 1091-6490
ENGELMAN JEFFREY A: "Targeting PI3K signalling in cancer: opportunities, challenges and limitations", NATURE REVIEWS CANCER, vol. 9, no. 8, August 2009 (2009-08-01), pages 550 - 562, XP002693047, ISSN: 1474-175X
GARCIA-ECHEVERRIA AND W R SELLERS C: "Drug discovery approaches targeting the PI3K/Akt pathway in cancer", ONCOGENE, NATURE PUBLISHING GROUP, GB, vol. 27, no. 41, 1 January 2008 (2008-01-01), pages 5511 - 5526, XP008153878, ISSN: 0950-9232, DOI: 10.1038/ONC.2008.246
NAGATA YOICHI ET AL: "PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients", CANCER CELL, CELL PRESS, US, vol. 6, no. 2, 1 August 2004 (2004-08-01), pages 117 - 127, XP002449979, ISSN: 1535-6108, DOI: 10.1016/J.CCR.2004.06.022
SANSAL I ET AL: "The Biology and Clinical Relevance of the PTEN Tumor Suppressor Pathway", JOURNAL OF CLINICAL ONCOLOGY, AMERICAN SOCIETY OF CLINICAL ONCOLOGY, US, vol. 22, no. 14, 15 July 2004 (2004-07-15), pages 2954 - 2963, XP003011859, ISSN: 0732-183X, DOI: 10.1200/JCO.2004.02.141
BOEHM JESSE S ET AL: "Integrative genomic approaches identify IKBKE as a breast cancer oncogene", CELL, CELL PRESS, US, vol. 129, no. 6, 1 June 2007 (2007-06-01), pages 1065 - 1079, XP002498282, ISSN: 0092-8674, DOI: 10.1016/J.CELL.2007.03.052
VASUDEVAN KRISHNA M ET AL: "AKT-Independent Signaling Downstream of Oncogenic PIK3CA Mutations in Human Cancer", CANCER CELL, vol. 16, no. 1, July 2009 (2009-07-01), pages 21 - 32, XP002693048, ISSN: 1535-6108
SERVANT, M.J. ET AL.: "The IKK-related kinases, unsuspected culprits in oncogenesis?", March 2009 (2009-03-01), XP002685965, Retrieved from the Internet
XIE XIAODUO ET AL: "IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 19 APR 2011 LNKD- PUBMED:21464307, vol. 108, no. 16, 19 April 2011 (2011-04-19), pages 6474 - 6479, XP002685966, ISSN: 1091-6490
ENGELMAN JEFFREY A: "Targeting PI3K signalling in cancer: opportunities, challenges and limitations", NATURE REVIEWS CANCER, vol. 9, no. 8, August 2009 (2009-08-01), pages 550 - 562, XP002693047, ISSN: 1474-175X
GARCIA-ECHEVERRIA AND W R SELLERS C: "Drug discovery approaches targeting the PI3K/Akt pathway in cancer", ONCOGENE, NATURE PUBLISHING GROUP, GB, vol. 27, no. 41, 1 January 2008 (2008-01-01), pages 5511 - 5526, XP008153878, ISSN: 0950-9232, DOI: 10.1038/ONC.2008.246
NAGATA YOICHI ET AL: "PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients", CANCER CELL, CELL PRESS, US, vol. 6, no. 2, 1 August 2004 (2004-08-01), pages 117 - 127, XP002449979, ISSN: 1535-6108, DOI: 10.1016/J.CCR.2004.06.022
SANSAL I ET AL: "The Biology and Clinical Relevance of the PTEN Tumor Suppressor Pathway", JOURNAL OF CLINICAL ONCOLOGY, AMERICAN SOCIETY OF CLINICAL ONCOLOGY, US, vol. 22, no. 14, 15 July 2004 (2004-07-15), pages 2954 - 2963, XP003011859, ISSN: 0732-183X, DOI: 10.1200/JCO.2004.02.141
BOEHM JESSE S ET AL: "Integrative genomic approaches identify IKBKE as a breast cancer oncogene", CELL, CELL PRESS, US, vol. 129, no. 6, 1 June 2007 (2007-06-01), pages 1065 - 1079, XP002498282, ISSN: 0092-8674, DOI: 10.1016/J.CELL.2007.03.052
VASUDEVAN KRISHNA M ET AL: "AKT-Independent Signaling Downstream of Oncogenic PIK3CA Mutations in Human Cancer", CANCER CELL, vol. 16, no. 1, July 2009 (2009-07-01), pages 21 - 32, XP002693048, ISSN: 1535-6108
Attorney, Agent or Firm:
SCOTT, Susan Margaret et al. (20 Red Lion Street, London WC1R 4PQ, GB)
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