Identifying off-target effects and hidden phenotypes of drugs in human cells

• Main Authors: SHANG ZHIDI, MICHNICK STEPHEN W, OWENS STEPHEN, BILTER GRAHAM K, MINAMI TOMOE, KEON BRIGITTE, MACDONALD MARNIE L, LAMERDIN JANE, DIAS JENNIFER, HUANG ZHENGPING, YU HELEN, WESTWICK JOHN K
• Format: Patent
• Language: English
• Published: 13.09.2007
• Subjects: BEER; BIOCHEMISTRY; CALCULATING; CHEMISTRY; COMPOSITIONS OR TEST PAPERS THEREFOR; COMPUTING; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL ORENZYMOLOGICAL PROCESSES; COUNTING; ELECTRIC DIGITAL DATA PROCESSING; ENZYMOLOGY; INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIRCHEMICAL OR PHYSICAL PROPERTIES; MEASURING; MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEICACIDS OR MICROORGANISMS; METALLURGY; MICROBIOLOGY; MUTATION OR GENETIC ENGINEERING; PHYSICS; PROCESSES OF PREPARING SUCH COMPOSITIONS; SPIRITS; TESTING; VINEGAR; WINE

This invention provides principles, methods and compositions for ascertaining the mechanism of action of pharmacologically important compounds in the context of network biology, across the entire scope of the complex pathways of living cells. Importantly, the principles, methods and compositions provided allow a rapid assessment of the on-pathway and off-pathway effects of lead compounds and drug candidates in living cells, and comparisons of lead compounds with well-characterized drugs and toxicants to identify patterns associated with efficacy and toxicity. The invention will be useful in improving the drug discovery process, in particular by identifying drug leads with desired safety and efficacy and in effecting early attrition of compounds with potential adverse effects in man.