METHODS AND COMPOSITIONS FOR RESTORING CONFORMATIONAL STABILITY OF PROTEIN OF THE p53 FAMILY

• Main Authors: BARBARA, ANN FOSTER, FARZAN, RASTINEJAD, RICHARD, DAMIAN CONNELL, HEATHER, ANNE COFFEY
• Format: Patent
• Language: English
• Published: 19.07.2005
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

The invention provides pharmaceutical non-peptidic organic compounds capable of interacting with a functionally defective form of a mutant or a wild-type tumor suppressor protein of the p53 family (such as p53, p63 or p73). The interaction allows stabilization or folding of the protein in a functional conformation, thereby restoring all or part of its wild-type normal activity. More particularly said compounds interact with the DNA binding domain of p53 family proteins, are acridine, quinoline, quinazoline or phenothiazine derivatives, and are used in cancer therapy. Also provided are methods for screening such pharmacological compounds. Pronalazak je iz oblasti tretmana raka. Naročito, ovaj pronalazak obezbedjuje farmaceutska jedinjenje sposobna da medjusobno deluju sa mutant i ne-mutant oblicima proteina koji se odnose na rak tako da mutant protein pojačava kapacitet za ispravno medjusobno delovanje sa drugim makromolekulima, čime se uspostavljaju ili stabilišu svi ili deo njihovih aktivnosti neobradjenog tipa. Regulacioni proteini uključuju članove iz p53 protein familije takve kao, na primer p53, p63 i p73. Jedinjenja iz pronalaska su korisna za tretman raka. Postupci za ekranizovanje takvih farmakoloških jedinjenja su takodje obezbedjeni.[The invention provides pharmaceutical non-peptidic organic compounds capable of interacting with a functionally defective form of a mutant or a wild-type tumor suppressor protein of the p53 family (such as p53, p63 or p73). The interaction allows stabilization or folding of the protein in a functional conformation, thereby restoring all or part of its wild-type normal activity. More particularly said compounds interact with the DNA binding domain of p53 family proteins, are acridine, quinoline, quinazoline or phenothiazine derivatives, and are used in cancer therapy. Also provided are methods for screening such pharmacological compounds.