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1. (WO1998051702) METHODS AND COMPOSITIONS FOR DESTRUCTION OF SELECTED PROTEINS
Latest bibliographic data on file with the International Bureau

Pub. No.: WO/1998/051702 International Application No.: PCT/US1998/009805
Publication Date: 19.11.1998 International Filing Date: 14.05.1998
Chapter 2 Demand Filed: 21.10.1998
IPC:
C07D 225/06 (2006.01) ,C07J 17/00 (2006.01) ,C07J 43/00 (2006.01)
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
D
HETEROCYCLIC COMPOUNDS
225
Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom
04
condensed with carbocyclic rings or ring systems
06
condensed with one six-membered ring
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
J
STEROIDS
17
Normal steroids containing carbon, hydrogen, halogen, or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta[a]hydrophenanthrene skeleton
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
J
STEROIDS
43
Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta[a]hydrophenanthrene skeleton
Applicants:
SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH [US/US]; 1275 York Avenue New York, NY 10021, US (AllExceptUS)
ROSEN, Neal [US/US]; US (UsOnly)
DANISHEFSKY, Samuel [US/US]; US (UsOnly)
OUERFELLI, Ouathek [TN/US]; US (UsOnly)
KUDUK, Scott, D. [US/US]; US (UsOnly)
SEPP-LORENZINO, Laura [US/US]; US (UsOnly)
Inventors:
ROSEN, Neal; US
DANISHEFSKY, Samuel; US
OUERFELLI, Ouathek; US
KUDUK, Scott, D.; US
SEPP-LORENZINO, Laura; US
Agent:
LARSON, Marina, T.; Oppedahl & Larson LLP P.O. Box 5270 Frisco, CO 80443-5270, US
Priority Data:
60/046,45114.05.1997US
Title (EN) METHODS AND COMPOSITIONS FOR DESTRUCTION OF SELECTED PROTEINS
(FR) METHODES ET COMPOSITIONS DE DESTRUCTION DE PROTEINES SELECTIONNEES
Abstract:
(EN) Compounds having an ansamycin antibiotic, or other moiety which binds to hsp90, coupled to a targeting moiety which binds specifically to a protein, receptor or marker can provide effective targeted delivery of the ansamycin antibiotic leading to the degradation of proteins and death of the targeted cells. These compositions may have different specificity than the ansamycin alone, allowing for a more specific targeting of the therapy, and can be effective in instances where the ansamycin alone has no effect. Thus, these compounds provide an entirely new class of targeted chemotherapy agents with application, depending on the nature of the targeting moiety, to treatment of a variety of different forms of cancer. Such agents can further be used to promote selective degradation of proteins associated with the pathogenesis of other diseases, including antigens associated with autoimmune disorders and pathogenic proteins associated with Alzheimer's disease. Exemplary targeting moieties which may be employed in compounds of the invention include testosterone, estradiol, tamoxifen and wortmannin.
(FR) L'invention concerne des composés comprenant un antibiotique d'ansamycine ou une autre fraction se liant à hsp90, couplés à une fraction cible qui se lie spécifiquement à une protéine, un récepteur ou un marqueur, et capables de favoriser une libération ciblée effective de l'antibiotique d'ansamycine entraînant la dégradation de protéines et la mort des cellules ciblées. Ces compositions peuvent présenter des particularités différentes de celles de l'ansamycine seule, ce qui permet un ciblage plus spécifique du traitement, et elles peuvent être efficaces dans des cas où l'ansamycine seule n'a pas d'effet. Ainsi, ces composés forment une classe entièrement nouvelle d'agents chimiothérapeutiques ciblés avec application, selon la nature de la fraction de ciblage, au traitement de plusieurs formes différentes de cancers. De tels agents peuvent également s'utiliser pour favoriser une dégradation sélective de protéines associées à la pathogenèse d'autres affections, y compris des antigènes associés à des troubles auto-immunes et des protéines pathogènes associées à la maladie d'Alzheimer. Des fractions de ciblage pouvant s'utiliser dans des composés de l'invention comprennent par exemple, du testostérone, de l'oestradiol, du tamoxifène et de la wortmannine.
Designated States: CA, JP, US
European Patent Office (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE)
Publication Language: English (EN)
Filing Language: English (EN)
Also published as:
EP1023315JP2009256388US6670348JP2001525824 CA2287387