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Ezh2 inhibitors and modulation of regulatory t-cell function

An inhibitor and inhibitory technology, applied in the direction of organic active ingredients, chemical instruments and methods, medical preparations containing active ingredients, etc.

Inactive Publication Date: 2018-06-08
CONSTELLATION PHARMA INC
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

Despite advances in the development of new EZH2 inhibitors as anticancer therapies, the patient populations in which these inhibitors are particularly effective remain unknown

Method used

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[0063] While a number of embodiments of this invention have been described, it is clear that our basic examples can be altered in order to provide other embodiments that utilize the compounds and methods of this disclosure. It is therefore to be understood that the scope of the disclosure is to be defined by the appended claims rather than by the specific embodiments which have been shown by way of example.

[0064] The contents of all documents (including literature references, issued patents, published patent applications, and co-pending patent applications) cited throughout this application are hereby incorporated by reference in their entirety. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art.

[0065] Inhibitor 1 was prepared according to the procedure described in: Bradley, W.D. et al. (2014), EZH2 Inhibitor Efficacy in Non-Hodgkin's Lymphoma Does Not Require Suppress...

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Abstract

Provided herein are methods of treating cancers characterized by a high frequency of one or more suppressive immune cells, comprising administering a therapeutically effective amount of an enhancer ofzeste homolog 2 (EZH2) inhibitor. Also provided are combination therapies using an EZH2 inhibitor and a second agent that is an immunomodulator.

Description

[0001] related application [0002] This application claims priority to US Provisional Application No. 62 / 200,244, filed August 3, 2015, the contents of which are incorporated herein in their entirety. Background technique [0003] A large number of small molecule inhibitors of Zeste enhancer homolog 2 (EZH2) are in clinical development for the treatment of various types of cancer. Despite advances in the development of new EZH2 inhibitors as anticancer therapies, it remains unknown which patient populations these inhibitors are particularly effective in. Patient populations particularly suitable for treatment with EZH2 inhibitors are disclosed herein. Contents of the invention [0004] Inhibition of EZH2 has now been found to reduce the proliferation of regulatory T cells (Treg), increase cytotoxic T cells (CD8), produce a favorable CD8 / Treg ratio, increase natural killer (NK) cells and natural killer T (NKT) cells, and Reduces M2 tumor-associated macrophages (TAMs). Bas...

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Application Information

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IPC IPC(8): A61K39/395A61K45/06A61K31/4439A61P35/00
CPCA61K45/06A61K39/3955C07K16/2818C07K2317/73C07K2317/76A61K31/4545A61P35/00A61K2300/00A61K2039/505
Inventor S·戈施J·M·洛拉
Owner CONSTELLATION PHARMA INC
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