Title:
INHIBITORS OF HUMAN EZH2, AND METHODS OF USE THEREOF
Document Type and Number:
Japanese Patent JP2019070653
Kind Code:
A
Abstract:
To provide inhibition of wild-type and certain mutant forms of human histone methyltransferase EZH2, the catalytic subunit of a PRC2 complex which catalyzes the mono- through tri-methylation of lysine 27 on histone H3 (H3-K27), methods for treating follicular lymphoma, and methods of determining responsiveness to an EZH2 inhibitor in a subject.SOLUTION: A method comprises the steps of: a) obtaining a tissue sample from a subject; b) detecting a dimethylation (me2) level of H3-K27, if present in the tissue sample, and comparing the dimethylation (me2) level to a control dimethylation (me2) level; and c) optionally detecting a trimethylation (me3) level of H3-K27, if present in the tissue sample, and comparing the trimethylation (me3) level to a control trimethylation (me3) level.SELECTED DRAWING: Figure 14
Inventors:
ROBERT ALLEN COPELAND
VICTORIA MARIE RICHON
MARGARET DAVIS SCOTT
CHRISOPHER JOHN SNEERINGER
KEVIN WAYNE KUNTZ
SARAH KATHLEEN KNUTSON
ROY MACFARLANE POLLOCK
VICTORIA MARIE RICHON
MARGARET DAVIS SCOTT
CHRISOPHER JOHN SNEERINGER
KEVIN WAYNE KUNTZ
SARAH KATHLEEN KNUTSON
ROY MACFARLANE POLLOCK
Application Number:
JP2018218823A
Publication Date:
May 09, 2019
Filing Date:
November 22, 2018
Export Citation:
Assignee:
EPIZYME INC
International Classes:
G01N33/53; A61K31/7076; A61K45/00; A61P35/00; A61P35/02; A61P43/00; C07H19/167; C12N5/09; C12N9/99; C12Q1/68; G01N33/15; G01N33/48; G01N33/50; G01N33/574
Domestic Patent References:
| JP2004217634A | 2004-08-05 | |||
| JP6389036B2 | 2018-09-12 |
Foreign References:
| WO2009124137A2 | 2009-10-08 | |||
| US20090012031A1 | 2009-01-08 |
Other References:
MORIN, R. D. ET AL.: "Somatic mutations altering EZH2(Tyr641) in follicular and diffuse lage B-cell lymphomas of germinal-", NATURE GENETICS, vol. 42, no. 2, JPN6015033259, 17 January 2010 (2010-01-17), pages 181 - 185, XP055101779, ISSN: 0004405734, DOI: 10.1038/ng.518
MIRANDA, T. B. ET AL.: "DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by", MOLECULAR CANCER THERAPEUTICS, vol. 8, no. 6, JPN6015033261, June 2009 (2009-06-01), pages 1579 - 1588, XP055049435, ISSN: 0004405735, DOI: 10.1158/1535-7163.MCT-09-0013
FISKUS, W. ET AL.: "Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A an", BLOOD, vol. 114, no. 13, JPN6020001516, September 2009 (2009-09-01), pages 2733 - 2743, XP055061501, ISSN: 0004405736, DOI: 10.1182/blood-2009-03-213496
MIRANDA, T. B. ET AL.: "DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by", MOLECULAR CANCER THERAPEUTICS, vol. 8, no. 6, JPN6015033261, June 2009 (2009-06-01), pages 1579 - 1588, XP055049435, ISSN: 0004405735, DOI: 10.1158/1535-7163.MCT-09-0013
FISKUS, W. ET AL.: "Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A an", BLOOD, vol. 114, no. 13, JPN6020001516, September 2009 (2009-09-01), pages 2733 - 2743, XP055061501, ISSN: 0004405736, DOI: 10.1182/blood-2009-03-213496
Attorney, Agent or Firm:
Hatsushi Shimizu
Masao Haruna
Hirotaka Yamaguchi
Toshi Gobe
Ryuichi Inoue
Toshimitsu Sato
Koichi Niimi
Tomohiko Kobayashi
Masato Ozeki
Yoshihiro Igarashi
Kazuya Kawamoto
Masao Haruna
Hirotaka Yamaguchi
Toshi Gobe
Ryuichi Inoue
Toshimitsu Sato
Koichi Niimi
Tomohiko Kobayashi
Masato Ozeki
Yoshihiro Igarashi
Kazuya Kawamoto