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1. WO2010030355 - TARGETED CHEMICAL HIGH-THROUGHPUT SCREENING METHOD

Publication Number WO/2010/030355
Publication Date 18.03.2010
International Application No. PCT/US2009/005075
International Filing Date 10.09.2009
IPC
C12Q 1/68 2006.1
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
1Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
68involving nucleic acids
C12Q 1/02 2006.1
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
1Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
02involving viable microorganisms
G01N 33/50 2006.1
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33Investigating or analysing materials by specific methods not covered by groups G01N1/-G01N31/131
48Biological material, e.g. blood, urine; Haemocytometers
50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
CPC
C12Q 1/6897
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS
1Measuring or testing processes involving enzymes, nucleic acids or microorganisms
68involving nucleic acids
6897involving reporter genes operably linked to promoters
G01N 33/5041
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
48Biological material, e.g. blood, urine
50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
5005involving human or animal cells
5008for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
502for testing non-proliferative effects
5041involving analysis of members of signalling pathways
Applicants
  • NEW YORK UNIVERSITY [US]/[US] (AllExceptUS)
  • DASGUPTA, Ramanuj [IN]/[US] (UsOnly)
  • GONSALVES, Foster [IN]/[US] (UsOnly)
Inventors
  • DASGUPTA, Ramanuj
  • GONSALVES, Foster
Agents
  • FASHENA, Sarah, J.
Priority Data
61/191,72310.09.2008US
Publication Language English (en)
Filing Language English (EN)
Designated States
Title
(EN) TARGETED CHEMICAL HIGH-THROUGHPUT SCREENING METHOD
(FR) PROCÉDÉ DE CRIBLAGE CHIMIQUE À HAUT DÉBIT CIBLÉ
Abstract
(EN) A novel method which integrates a "sensitized" chemical genetic high-throughput screen (HTS) with RNA interference (RNAi) screening technology is described herein. The present inventors used this method to identify specific small molecule inhibitors and activators of the Wnt pathway. More particularly, the screening method of the present invention may be used to identify small molecule inhibitors and activators that specifically target the activity of a stabilized pool of β-catenin. A number of compounds identified using the instant method, are shown herein to be small molecule inhibitors of the Wnt pathway that specifically target the activity of the stabilized pool of β-cat. The inhibitors identified by the present method may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, cancer, and others.
(FR) La présente invention concerne un nouveau procédé qui intègre un crible génétique chimique à haut débit (HTS) « sensibilisé » doté d'une technologie de criblage par interférence ARN (ARNi). Les présents inventeurs ont utilisé ce procédé pour identifier des inhibiteurs et des activateurs spécifiques à base de petites molécules de la voie du Wnt. Plus particulièrement, le procédé de criblage de la présente invention peut être utilisé pour identifier des inhibiteurs et des activateurs à base de petites molécules qui ciblent spécifiquement l'activité d'un ensemble stabilisé de β-caténine. On montre ici qu’un certain nombre de composés identifiés en utilisant le présent procédé sont des inhibiteurs à base de petites molécules de la voie du Wnt qui ciblent spécifiquement l'activité de l'ensemble stabilisé de β-cat. Les inhibiteurs identifiés par le présent procédé peuvent être préparés sous la forme de compositions pharmaceutiques, et peuvent être utilisés pour la prévention et le traitement d'une variété d'états chez des mammifères y compris des humains, comprenant, en tant qu'exemple non limitant, le cancer, et autres.
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