Title:
CRYSTAL STRUCTURE AND PEPTIDE INHIBITORS OF HAUSP DEUBIQUITINASE
Document Type and Number:
WIPO Patent Application WO/2012/141794
Kind Code:
A3
Abstract:
Two vIRF4 (Kaposi's-sarcoma-associated-herpesvirus vIRF4) peptides, vif1, corresponding to aa202-216 of vIRF4, and vif2, corresponding to aa220-236 of vIRF4, are potent and selective HAUSP antagonists. The vif1 and vif2 peptides robustly suppress HAUSP DUB enzymatic activity, ultimately leading to p53 -mediated anti-cancer activity. The vif1 and vif2 peptides, along with their homologues, are useful in treating cancer through regulation of p53 activity in a cancer cell. Also disclosed is the crystalline structure of vIRF4-HAUSP TRAF domain complex. The structure is useful in computer aided drug design for identifying an agent that interacts with and inhibits HAUSP, resulting in p53 medicated cell cycle arrest of cancer cells.
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Inventors:
JUNG JAE (US)
LEE HYE-RA (US)
KIM MYUNG HEE (KR)
OH TAE-KWANG (KR)
HWANG JUNG-WON (KR)
LEE HYE-RA (US)
KIM MYUNG HEE (KR)
OH TAE-KWANG (KR)
HWANG JUNG-WON (KR)
Application Number:
PCT/US2012/026198
Publication Date:
March 14, 2013
Filing Date:
February 22, 2012
Export Citation:
Assignee:
UNIV SOUTHERN CALIFORNIA (US)
KOREA RES INST OF BIOSCIENCE & BIOTECHNOLOGY (KR)
JUNG JAE (US)
LEE HYE-RA (US)
KIM MYUNG HEE (KR)
OH TAE-KWANG (KR)
HWANG JUNG-WON (KR)
KOREA RES INST OF BIOSCIENCE & BIOTECHNOLOGY (KR)
JUNG JAE (US)
LEE HYE-RA (US)
KIM MYUNG HEE (KR)
OH TAE-KWANG (KR)
HWANG JUNG-WON (KR)
International Classes:
A61K38/17; A61K38/16; A61K48/00; A61P35/00
Foreign References:
| US6348586B1 | 2002-02-19 |
Other References:
HYE RA LEE ET AL.: "'Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 4 Targets MDM2 To Deregulate the p53 Tumor Suppressor Pathway'", JOURNAL OF VIROLOGY, vol. 83, no. 13, 2009, pages 6739 - 6747
KATHARINA HEINZELMANN ET AL.: "'Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 4 (vIRF4/K10) Is a Novel Interaction Partner of CSL/CBF1, the Major Downstream Effector of Notch Signaling'", JOURNAL OF VIROLOGY, vol. 84, no. 23, 2010, pages 12255 - 12264
HYE RA LEE ET AL.: "Viral Interferon Regulatory Factors", JOURNAL OF INTERFERON & CYTOKINE RESEARCH, vol. 29, no. 9, 2009, pages 621 - 627
KATHARINA HEINZELMANN ET AL.: "'Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 4 (vIRF4/K10) Is a Novel Interaction Partner of CSL/CBF1, the Major Downstream Effector of Notch Signaling'", JOURNAL OF VIROLOGY, vol. 84, no. 23, 2010, pages 12255 - 12264
HYE RA LEE ET AL.: "Viral Interferon Regulatory Factors", JOURNAL OF INTERFERON & CYTOKINE RESEARCH, vol. 29, no. 9, 2009, pages 621 - 627
Attorney, Agent or Firm:
KONSKI, Antoinette, F. et al. (975 Page Mill RoadPalo Alto, CA, US)
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