Title:
TISSUE SPECIFIC PRODRUGS
Document Type and Number:
WIPO Patent Application WO2002043773
Kind Code:
A3
Abstract:
The invention provides novel peptide prodrugs which contain cleavage sites specifically cleaved by prostate specific membrane antigen (PSMA). These prodrugs are useful for substantially inhibiting the non-specific toxicity of a variety of therapeutic drugs. PSMA is secreted by prostatic glandular cells. Upon cleavage of the prodrug by PSMA, the therapeutic drug are activated and exert their toxicity. Sesquiterpene- gamma -lactones form part of the prodrugs, and are designed to be linked to carrier moieties such as the peptides of the invention. Methods for treating cell proliferative disorders are also featured in the invention.
Inventors:
ISAACS JOHN T (US)
DENMEADE SAMUEL R (US)
DENMEADE SAMUEL R (US)
Application Number:
PCT/US2001/045100
Publication Date:
August 21, 2003
Filing Date:
November 30, 2001
Export Citation:
Assignee:
UNIV JOHNS HOPKINS (US)
ISAACS JOHN T (US)
DENMEADE SAMUEL R (US)
ISAACS JOHN T (US)
DENMEADE SAMUEL R (US)
International Classes:
A61K47/48; C07K5/072; C07K5/093; C07K5/113; C07K7/06; G01N33/574; A61K38/00; (IPC1-7): A61K47/48
Domestic Patent References:
| WO1998003873A1 | 1998-01-29 | |||
| WO1998052966A1 | 1998-11-26 | |||
| WO2001062300A2 | 2001-08-30 | |||
| WO2002022833A1 | 2002-03-21 | |||
| WO2002098885A1 | 2002-12-12 |
Other References:
RAWLINGS NEIL D ET AL: "Structure of membrane glutamate carboxypeptidase.", BIOCHIMICA ET BIOPHYSICA ACTA, vol. 1339, no. 2, 1997, pages 247 - 252, XP004281549, ISSN: 0006-3002
HESTON W D: "Characterization and glutamyl preferring carboxypeptidase function of prostate specific membrane antigen: a novel folate hydrolase.", UROLOGY. UNITED STATES MAR 1997, vol. 49, no. 3A Suppl, March 1997 (1997-03-01), pages 104 - 112, XP002238194, ISSN: 0090-4295
GRASSO YING Z ET AL: "Prostate-specific membrane antigen as a target for prodrug therapy: Relationship between its folate hydrolase and endocytosis activities.", PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH ANNUAL, vol. 42, March 2001 (2001-03-01), 92nd Annual Meeting of the American Association for Cancer Research;New Orleans, LA, USA; March 24-28, 2001, March, 2001, pages 777, XP002238195, ISSN: 0197-016X
HESTON W D: "Characterization and glutamyl preferring carboxypeptidase function of prostate specific membrane antigen: a novel folate hydrolase.", UROLOGY. UNITED STATES MAR 1997, vol. 49, no. 3A Suppl, March 1997 (1997-03-01), pages 104 - 112, XP002238194, ISSN: 0090-4295
GRASSO YING Z ET AL: "Prostate-specific membrane antigen as a target for prodrug therapy: Relationship between its folate hydrolase and endocytosis activities.", PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH ANNUAL, vol. 42, March 2001 (2001-03-01), 92nd Annual Meeting of the American Association for Cancer Research;New Orleans, LA, USA; March 24-28, 2001, March, 2001, pages 777, XP002238195, ISSN: 0197-016X
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