Title:
USING MULTIPLE PERTURBATIONS TO ELUCIDATE CONNECTIVITY IN NETWORK SYSTEMS
Document Type and Number:
WIPO Patent Application WO2005031584
Kind Code:
A3
Abstract:
One embodiment of the invention is a method of analyzing the effects of combined perturbers of a network system by means of a set of model predictions for various network configurations, using a set of phenomenologically-based combination surface models. This method can be used to predict the effects of combined perturbers of known networks, for example, providing mechanistic validation for therapeutic compounds. Alternatively, this method can provide constraints for constructing connectivity models from observed combination effects on networks of unknown structure, thus, for example, providing the required understanding to identify novel targets for therapeutic compounds.
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Inventors:
LEHAR JOSEPH (US)
MOLNAR RAYMOND A (US)
KEITH CURTIS T (US)
ZIMMERMANN GRANT (US)
MOLNAR RAYMOND A (US)
KEITH CURTIS T (US)
ZIMMERMANN GRANT (US)
Application Number:
PCT/US2004/032124
Publication Date:
April 13, 2006
Filing Date:
September 27, 2004
Export Citation:
Assignee:
COMBINATORX INC (US)
LEHAR JOSEPH (US)
MOLNAR RAYMOND A (US)
KEITH CURTIS T (US)
ZIMMERMANN GRANT (US)
LEHAR JOSEPH (US)
MOLNAR RAYMOND A (US)
KEITH CURTIS T (US)
ZIMMERMANN GRANT (US)
International Classes:
G06F13/00; G01N33/48; G01N33/50; G06F19/00; G06G7/48; G06G7/58; G16B5/00
Other References:
GROTEN J P ET AL: "Toxicology of simple and complex mixtures", TRENDS IN PHARMACOLOGICAL SCIENCES, ELSEVIER, HAYWARTH, GB, vol. 22, no. 6, 1 June 2001 (2001-06-01), pages 316 - 322, XP004241904, ISSN: 0165-6147
BORISY ALEXIS A ET AL: "Systematic discovery of multicomponent therapeutics.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 100, no. 13, 24 June 2003 (2003-06-24), pages 7977 - 7982, XP009061663, ISSN: 0027-8424
MELETIADIS JOSEPH ET AL: "In vitro drug interaction modeling of combinations of azoles with terbinafine against clinical Scedosporium prolificans isolates.", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 47, no. 1, January 2003 (2003-01-01), pages 106 - 117, XP009061697, ISSN: 0066-4804
GRECO W R ET AL: "APPLICATION OF A NEW APPROACH FOR THE QUANTITATION OF DRUG SYNERGISM TO THE COMBINATION OF CIS-DIAMMINEDICHLOROPLATINUM AND 1-BETA-D-ARABINOFURANOSYLCYTOSINE", CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, BALTIMORE, MD, US, vol. 50, no. 17, 1 September 1990 (1990-09-01), pages 5318 - 5327, XP001207322, ISSN: 0008-5472
JACKSON R C: "AMPHIBOLIC DRUG COMBINATIONS: THE DESIGN OF SELECTIVE ANTIMETABOLITE PROTOCOLS BASED UPON THE KINETIC PROPERTIES OF MULTIENZYME SYSTEMS", CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, BALTIMORE, MD, US, vol. 53, no. 17, 1 September 1993 (1993-09-01), pages 3998 - 4003, XP001207439, ISSN: 0008-5472
CHOU T C ET AL: "QUANTITATIVE ANALYSIS OF DOSE-EFFECT RELATIONSHIPS: THE COMBINED EFFECTS OF MULTIPLE DRUGS OR ENZYME INHIBITORS", ADVANCES IN ENZYME REGULATION, PERGAMON PRESS, OXFORD, GB, vol. 22, 1984, pages 27 - 55, XP000941165, ISSN: 0065-2571
BORISY ALEXIS A ET AL: "Systematic discovery of multicomponent therapeutics.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 100, no. 13, 24 June 2003 (2003-06-24), pages 7977 - 7982, XP009061663, ISSN: 0027-8424
MELETIADIS JOSEPH ET AL: "In vitro drug interaction modeling of combinations of azoles with terbinafine against clinical Scedosporium prolificans isolates.", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 47, no. 1, January 2003 (2003-01-01), pages 106 - 117, XP009061697, ISSN: 0066-4804
GRECO W R ET AL: "APPLICATION OF A NEW APPROACH FOR THE QUANTITATION OF DRUG SYNERGISM TO THE COMBINATION OF CIS-DIAMMINEDICHLOROPLATINUM AND 1-BETA-D-ARABINOFURANOSYLCYTOSINE", CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, BALTIMORE, MD, US, vol. 50, no. 17, 1 September 1990 (1990-09-01), pages 5318 - 5327, XP001207322, ISSN: 0008-5472
JACKSON R C: "AMPHIBOLIC DRUG COMBINATIONS: THE DESIGN OF SELECTIVE ANTIMETABOLITE PROTOCOLS BASED UPON THE KINETIC PROPERTIES OF MULTIENZYME SYSTEMS", CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, BALTIMORE, MD, US, vol. 53, no. 17, 1 September 1993 (1993-09-01), pages 3998 - 4003, XP001207439, ISSN: 0008-5472
CHOU T C ET AL: "QUANTITATIVE ANALYSIS OF DOSE-EFFECT RELATIONSHIPS: THE COMBINED EFFECTS OF MULTIPLE DRUGS OR ENZYME INHIBITORS", ADVANCES IN ENZYME REGULATION, PERGAMON PRESS, OXFORD, GB, vol. 22, 1984, pages 27 - 55, XP000941165, ISSN: 0065-2571
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