Title:
MODIFIED GLUCOCORTICOID RECEPTORS, GLUCOCORTICOID RECEPTORS/PROGESTERONE RECEPTORS HYBRIDS
Document Type and Number:
WIPO Patent Application WO1998018925
Kind Code:
A3
Abstract:
The present invention provides mutant proteins of steroid hormone receptors. These mutant proteins are useful in methods of distinguishing a steroid hormone receptor antagonist from a steroid hormone receptor agonist. The present invention also provides plasmids containing mutated steroid hormone receptor proteins and cells transfected with those plasmids. In addition, the present invention provides methods for determining whether a compound is a steroid hormone receptor antagonist or agonist. Also, the present invention provides methods of determining endogenous ligands for steroid hormone receptors. The invention further provides a molecular switch protein for regulating expression in gene therapy.
Inventors:
O'MALLEY BERT (US)
TSAI MING-JER (US)
TSAI SOPHIA Y (US)
KITTLE JOSEPH D JR (US)
LEDEBUR HARRY C JR (US)
WANG YAOLIN (US)
TSAI MING-JER (US)
TSAI SOPHIA Y (US)
KITTLE JOSEPH D JR (US)
LEDEBUR HARRY C JR (US)
WANG YAOLIN (US)
Application Number:
PCT/US1997/019607
Publication Date:
October 15, 1998
Filing Date:
October 28, 1997
Export Citation:
Assignee:
GENEMEDICINE INC (US)
BAYLOR COLLEGE MEDICINE (US)
MALLEY BERT O (US)
TSAI MING JER (US)
TSAI SOPHIA Y (US)
KITTLE JOSEPH D JR (US)
LEDEBUR HARRY C JR (US)
WANG YAOLIN (US)
BAYLOR COLLEGE MEDICINE (US)
MALLEY BERT O (US)
TSAI MING JER (US)
TSAI SOPHIA Y (US)
KITTLE JOSEPH D JR (US)
LEDEBUR HARRY C JR (US)
WANG YAOLIN (US)
International Classes:
A01K67/027; A61K38/00; A61K48/00; A61P11/06; A61P19/02; A61P25/28; C07K14/72; C12N5/10; C12N15/09; C12N15/12; C12N15/63; C12N15/82; G01N33/566; G01N33/74; (IPC1-7): C12N15/12; C12N15/62; C07K14/72; A61K38/17; A01K67/027
Domestic Patent References:
| WO1996040911A1 | 1996-12-19 | |||
| WO1993023431A1 | 1993-11-25 | |||
| WO1990007517A1 | 1990-07-12 | |||
| WO1990014356A1 | 1990-11-29 | |||
| WO1992022567A1 | 1992-12-23 |
Foreign References:
| EP0371820A2 | 1990-06-06 |
Other References:
VINCENT LAUDET, DOMINIQUE STÉHELIN: "Les récepteurs nucléaires", POUR LA SCIENCE, PARIS, vol. 183, January 1993 (1993-01-01), pages 32 - 39, XP002058341
KELLENDONK ET AL.: "Regulation of Cre recombinase activity by the synthetic steroid RU 486", NUCLEIC ACIDS RESEARCH., vol. 24, no. 8, OXFORD GB, pages 1404 - 1411, XP002071703
VELDSCHOLTE J ET AL.: "Anti-androgens and the mutated androgen receptor of LNCaP cells: differential effects on binding affinity, heat-shock protein interaction, and transcription activation.", BIOCHEMISTRY., vol. 31, 1992, EASTON, PA US, pages 2393 - 2399, XP002071704
LANZ RB;RUSCONI S: "A conserved carboxy-terminal subdomain is important for ligand interpretation and transactivation by nuclear receptors.", ENDOCRINOLOGY, vol. 135, no. 5, 1994, pages 2183 - 2195, XP002071705
LEWIN, BENJAMIN: "Genes V", 1994, OXFORD UNIVERSTITY PRESS, OXFORD, GB, XP002058342, 205070
MALCHOFF D M ET AL: "A MUTATION OF THE GLUCOCORTICOID RECEPTOR IN PRIMARY CORTISOL RESISTANCE", JOURNAL OF CLINICAL INVESTIGATION, vol. 91, no. 5, May 1993 (1993-05-01), pages 1918 - 1925, XP000610522
WURTZ J -M ET AL: "A CANONICAL STRUCTURE FOR THE LIGAND-BINDING DOMAIN OF NUCLEAR RECEPTORS", NATURAL STRUCTURAL BIOLOGY, vol. 3, 1996, pages 87 - 94, XP000610199
LANZ, R.B. ETAL.;: "Active, interactive, and inactive steroid receptos mutants", STEOIDS, no. 59, September 1994 (1994-09-01), pages 148 - 152, XP002071954
KELLENDONK ET AL.: "Regulation of Cre recombinase activity by the synthetic steroid RU 486", NUCLEIC ACIDS RESEARCH., vol. 24, no. 8, OXFORD GB, pages 1404 - 1411, XP002071703
VELDSCHOLTE J ET AL.: "Anti-androgens and the mutated androgen receptor of LNCaP cells: differential effects on binding affinity, heat-shock protein interaction, and transcription activation.", BIOCHEMISTRY., vol. 31, 1992, EASTON, PA US, pages 2393 - 2399, XP002071704
LANZ RB;RUSCONI S: "A conserved carboxy-terminal subdomain is important for ligand interpretation and transactivation by nuclear receptors.", ENDOCRINOLOGY, vol. 135, no. 5, 1994, pages 2183 - 2195, XP002071705
LEWIN, BENJAMIN: "Genes V", 1994, OXFORD UNIVERSTITY PRESS, OXFORD, GB, XP002058342, 205070
MALCHOFF D M ET AL: "A MUTATION OF THE GLUCOCORTICOID RECEPTOR IN PRIMARY CORTISOL RESISTANCE", JOURNAL OF CLINICAL INVESTIGATION, vol. 91, no. 5, May 1993 (1993-05-01), pages 1918 - 1925, XP000610522
WURTZ J -M ET AL: "A CANONICAL STRUCTURE FOR THE LIGAND-BINDING DOMAIN OF NUCLEAR RECEPTORS", NATURAL STRUCTURAL BIOLOGY, vol. 3, 1996, pages 87 - 94, XP000610199
LANZ, R.B. ETAL.;: "Active, interactive, and inactive steroid receptos mutants", STEOIDS, no. 59, September 1994 (1994-09-01), pages 148 - 152, XP002071954
Download PDF: