Title:
INHIBITORS OF PDE4 BINDING TO HSP20
Document Type and Number:
WIPO Patent Application WO/2012/046008
Kind Code:
A3
Abstract:
The present invention provides methods and materials for use in increasing HSP20 activation in a biological system, for example by increasing phosphorylation of Ser16 of HSP20. In one aspect, the invention provides a method for increasing HSP20 activation in a biological system, comprising contacting the system with an antagonist capable of inhibiting PDE4 binding to HSP20, the antagonist comprising or consisting essentially of a fragment of PDE4 or an analogue thereof. In a further aspect the invention provides a method of screening for an agent able to increase activation of HSP20. A preferred antagonist has a C-termina! lysine residue.
Inventors:
BAILLIE GEORGE (GB)
HOUSLAY MILES (GB)
DAY JON (GB)
HOUSLAY MILES (GB)
DAY JON (GB)
Application Number:
PCT/GB2011/001457
Publication Date:
October 11, 2012
Filing Date:
October 07, 2011
Export Citation:
Assignee:
UNIV GLASGOW (GB)
BAILLIE GEORGE (GB)
HOUSLAY MILES (GB)
DAY JON (GB)
BAILLIE GEORGE (GB)
HOUSLAY MILES (GB)
DAY JON (GB)
International Classes:
A61K38/46; A61P9/04
Domestic Patent References:
| WO2010115141A2 | 2010-10-07 |
Other References:
ANONYMOUS: "3rd International Meeting on Anchored cAMP Signalling Pathways, Oslo, Norway, Wednesday September 29 - Thursday September 30, 2010", 30 July 2012 (2012-07-30), pages 1 - 3, XP055034110, Retrieved from the Internet [retrieved on 20120730]
ANONYMOUS: "3rd International Meeting on Anchored cAMP Signalling Pathways", 9 November 2011 (2011-11-09), pages 1, Retrieved from the Internet [retrieved on 20120730]
SIN Y Y ET AL: "Disruption of the cyclic AMP phosphodiesterase-4 (PDE4) HSP20 complex attenuates the -agonist induced hypertrophic response in cardiac myocytes", JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, ACADEMIC PRESS, GB, vol. 50, no. 5, 10 February 2011 (2011-02-10), pages 872 - 883, XP028189058, ISSN: 0022-2828, [retrieved on 20110218], DOI: 10.1016/J.YJMCC.2011.02.006
GUO-CHANG FAN ET AL: "Small heat shock protein 20 (HspB6) in cardiac hypertrophy and failure", JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, ACADEMIC PRESS, GB, vol. 51, no. 4, 23 September 2010 (2010-09-23), pages 574 - 577, XP028292073, ISSN: 0022-2828, [retrieved on 20100923], DOI: 10.1016/J.YJMCC.2010.09.013
VICTOR J. HRUBY: "Designing peptide receptor agonists and antagonists", NATURE REVIEWS DRUG DISCOVERY, vol. 1, no. 11, 1 November 2002 (2002-11-01), pages 847 - 858, XP055034286, ISSN: 1474-1776, DOI: 10.1038/nrd939
HOUSLAY M D ET AL: "Keynote review: Phosphodiesterase-4 as a therapeutic target", DRUG DISCOVERY TODAY, ELSEVIER, RAHWAY, NJ, US, vol. 10, no. 22, 15 November 2005 (2005-11-15), pages 1503 - 1519, XP027684942, ISSN: 1359-6446, [retrieved on 20051115]
GLOVER D K ET AL: "REDUCTION OF INFARCT SIZE AND POSTISCHEMIC INFLAMMATION FROM ATL-146E, A HIGHLY SELECTIVE ADENOSINE A2A RECEPTOR AGONIST, IN REPERFUSED CANINE MYOCARDIUM", AMERICAN JOURNAL OF PHYSIOLOGY: HEART AND CIRCULATORY PHYSIOLOGY, AMERICAN PHYSIOLOGICAL SOCIETY, US, vol. 288, no. 4, 1 April 2005 (2005-04-01), pages H1851 - H1858, XP008049688, ISSN: 0363-6135, DOI: 10.1152/AJPHEART.00362.2004
ANONYMOUS: "3rd International Meeting on Anchored cAMP Signalling Pathways", 9 November 2011 (2011-11-09), pages 1, Retrieved from the Internet
SIN Y Y ET AL: "Disruption of the cyclic AMP phosphodiesterase-4 (PDE4) HSP20 complex attenuates the -agonist induced hypertrophic response in cardiac myocytes", JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, ACADEMIC PRESS, GB, vol. 50, no. 5, 10 February 2011 (2011-02-10), pages 872 - 883, XP028189058, ISSN: 0022-2828, [retrieved on 20110218], DOI: 10.1016/J.YJMCC.2011.02.006
GUO-CHANG FAN ET AL: "Small heat shock protein 20 (HspB6) in cardiac hypertrophy and failure", JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, ACADEMIC PRESS, GB, vol. 51, no. 4, 23 September 2010 (2010-09-23), pages 574 - 577, XP028292073, ISSN: 0022-2828, [retrieved on 20100923], DOI: 10.1016/J.YJMCC.2010.09.013
VICTOR J. HRUBY: "Designing peptide receptor agonists and antagonists", NATURE REVIEWS DRUG DISCOVERY, vol. 1, no. 11, 1 November 2002 (2002-11-01), pages 847 - 858, XP055034286, ISSN: 1474-1776, DOI: 10.1038/nrd939
HOUSLAY M D ET AL: "Keynote review: Phosphodiesterase-4 as a therapeutic target", DRUG DISCOVERY TODAY, ELSEVIER, RAHWAY, NJ, US, vol. 10, no. 22, 15 November 2005 (2005-11-15), pages 1503 - 1519, XP027684942, ISSN: 1359-6446, [retrieved on 20051115]
GLOVER D K ET AL: "REDUCTION OF INFARCT SIZE AND POSTISCHEMIC INFLAMMATION FROM ATL-146E, A HIGHLY SELECTIVE ADENOSINE A2A RECEPTOR AGONIST, IN REPERFUSED CANINE MYOCARDIUM", AMERICAN JOURNAL OF PHYSIOLOGY: HEART AND CIRCULATORY PHYSIOLOGY, AMERICAN PHYSIOLOGICAL SOCIETY, US, vol. 288, no. 4, 1 April 2005 (2005-04-01), pages H1851 - H1858, XP008049688, ISSN: 0363-6135, DOI: 10.1152/AJPHEART.00362.2004
Attorney, Agent or Firm:
FORREST, Graham, R. et al. (33 Gutter LaneLondon, EC2V 8AS, GB)
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