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HUMAN EZH2 INHIBITORS AND WAYS OF THEIR APPLICATION
专利权人:
ЭПИЗАЙМ; ИНК. (US)
发明人:
КУНТЦ Кевин Уэйн (US),НАТСОН Сара Кейтлин (US),ВИГЛ Тимоти Джеймс Нельсон (US)
申请号:
RU2014141045
公开号:
RU2014141045A
申请日:
2013.03.12
申请国别(地区):
RU
年份:
2016
代理人:
摘要:
1. A method of treating or alleviating a cancer symptom or precancerous condition in an individual, comprising administering to a person expressing a mutant EZH2 containing a mutation in the substrate pocket domain, as defined in the sequence represented by SEQ ID NO: 6, of a therapeutically effective amount of an EZH2.2 inhibitor. The method of claim 1, wherein the mutant EZH2 is a mutant EZH2 polypeptide or a nucleic acid sequence encoding a mutant EZH2.3 polypeptide. The method of claim 1, wherein the cancer is lymphoma, leukemia, or melanoma. The method of claim 3, wherein the lymphoma is selected from the group consisting of non-Hodgkin lymphoma, follicular lymphoma, and diffuse large-cell B-cell lymphoma. The method of claim 3, wherein the leukemia is chronic myelogenous leukemia (CML). The method of claim 1, wherein the precancerous condition is myelodysplasia syndromes (MDS, formerly known as pre-leukemia syndrome). The method of claim 1, wherein the mutant EZH2 comprises a mutation at amino acid position 677, 687, 674, 685 or 641 of the sequence represented by SEQ ID NO: 1.8. The method of claim 7, wherein said mutation is selected from the group consisting of glycine (G) substitution of a wild-type alanine residue (A) at amino acid position 677 of the sequence represented by SEQ ID NO: 1 (A677G); substitution by valine (V) of the wild-type alanine residue (A) at amino acid position 687 of the sequence represented by SEQ ID NO: 1 (A687V); substituting methionine (M) for the wild-type valine (V) residue at amino acid position 674 of the sequence represented by SEQ ID NO: 1 (V674M); substitution by histidine (H) of the wild-type arginine (R) residue at amino acid position 685 of the sequence represented by SEQ ID NO: 1 (R685H); substitution by cysteine (C) of the wild-type arginine (R) residue at amino acid position 685 sequentially1. Способ лечения или облегчения симптома рака или предракового состояния у индивида, включающий введение индивиду, экспрессирующ
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