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Small molecule HSP70 inhibitors
专利权人:
发明人:
Donna L. George,Maureen E. Murphy,Julia I-Ju Leu
申请号:
US15121345
公开号:
US10010560B2
申请日:
2015.02.26
申请国别(地区):
US
年份:
2018
代理人:
摘要:
In an effort to discover therapies for treating HSP70 related diseases, a previously unidentified hydrophobic pocket was found in the C-terminal domain of DnaK and of human HSP70. A novel chemical scaffold was also discovered for identifying compounds that treat diseases related to this hydrophobic pocket. The compounds have the structure of the formula (I), wherein L, M, and R1-R5 are defined herein and are, therefore, in these therapies, optionally with other pharmaceutical agents such as genotoxic agents. Accordingly these compounds are useful in inhibiting HSP70 or DnaK, reducing HSP70 in mitochondria of a cancer cell, treating malignant neoplastic disease, or inhibiting or reducing bacterial growth. These compounds also resulted in novel methods of screening for a HSP70 inhibitor or DnaK inhibitor by using the three-dimensional structure of the hydrophobic pocket in DnaK or HSP70.
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