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1. WO2008122038 - REGULATING AUTOPHAGY

Publication Number WO/2008/122038
Publication Date 09.10.2008
International Application No. PCT/US2008/059129
International Filing Date 02.04.2008
IPC
A61K 31/405 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
33Heterocyclic compounds
395having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
40having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
403condensed with carbocyclic rings, e.g. carbazole
404Indoles, e.g. pindolol
405Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
CPC
A61K 31/405
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
33Heterocyclic compounds
395having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
40having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
403condensed with carbocyclic rings, e.g. carbazole
404Indoles, e.g. pindolol
405Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
C07D 487/14
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
DHETEROCYCLIC COMPOUNDS
487Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by C07D451/00 - C07D477/00
12in which the condensed system contains three hetero rings
14Ortho-condensed systems
Applicants
  • PRESIDENT AND FELLOWS OF HARVARD COLLEGE [US]/[US] (AllExceptUS)
  • DANA-FARBER CANCER INSTITUTE, INC. [US]/[US] (AllExceptUS)
  • CAMBRIDGE ENTERPRISE LTD. [GB]/[GB] (AllExceptUS)
  • YALE UNIVERSITY [US]/[US] (AllExceptUS)
  • BRADNER, James, Elliot [US]/[US] (UsOnly)
  • SHEN, John, Paul [US]/[US] (UsOnly)
  • PERLSTEIN, Ethan, Oren [US]/[US] (UsOnly)
  • RUBINSZTEIN, David [GB]/[GB] (UsOnly)
  • SARKAR, Sovan [IN]/[IN] (UsOnly)
  • SCHREIBER, Stuart, L. [US]/[US] (UsOnly)
  • WOOD, John [US]/[US] (UsOnly)
Inventors
  • BRADNER, James, Elliot
  • SHEN, John, Paul
  • PERLSTEIN, Ethan, Oren
  • RUBINSZTEIN, David
  • SARKAR, Sovan
  • SCHREIBER, Stuart, L.
  • WOOD, John
Agents
  • BAKER, C., Hunter
Priority Data
60/909,64002.04.2007US
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) REGULATING AUTOPHAGY
(FR) AUTOPHAGIE RÉGULATRICE
Abstract
(EN)
Autophagy is a cellular process by which cells canabalize non-essential cellular elements such as organelles to generate metabolites, or in some cases, to cause cell death. The present invention provides modulators of autophagy, which have been identified using a high-throughput phenotypic screen of over 3500 compounds. These modulators are useful in treating diseases ranging from proliferative diseases to neurodegenerative diseases to infectious diseases to protein misfolding states. Furthermore, the invention provides the treatment of proliferative disease such as cancer with a combination of autophagy inhibitors and protein kinase inhibitors.
(FR)
L'invention concerne l'autophagie, qui est un processus cellulaire par lequel des cellules cannibalisent des éléments cellulaires non essentiels tels que des organelles pour générer des métabolites, ou dans certains cas, pour provoquer une mort cellulaire. La présente invention propose des modulateurs de l'autophagie, qui ont été identifiés en utilisant un criblage phénotypique de capacité élevée sur plus de 3 500 composés. Ces modulateurs sont utiles pour traiter des maladies allant des maladies prolifératives aux maladies neurodégénératives jusqu'aux maladies infectieuses à des états de mauvais repliement de protéine. De plus, l'invention propose un traitement d'une maladie proliférative telle que le cancer avec une combinaison d'inhibiteurs d'autophagie et d'inhibiteurs de protéine kinase.
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