Inventors:
Nathanael Gray - Boston MA, US
Jae Won Chang - Boston MA, US
Jianming Zhang - Cambridge MA, US
Carson C. Thoreen - Jamaica Plain MA, US
Seong Woo Anthony Kang - Cambridge MA, US
David M. Sabatini - Cambridge MA, US
Qingsong Liu - Jamaica Plain MA, US
Assignee:
Dana-Farber Cancer Institute, Inc. - Boston MA
Whitehead Institute for Biomedical Research - Cambridge MA
International Classification:
A61K 31/4375
C07D 471/06
Abstract:
The present invention relates to small molecule modulators of mTORC1 and mTORC2, syntheses thereof, and intermediates thereto. Such small molecule modulators are useful in the treatment of proliferative diseases (e. g. , benign neoplasms, cancers, inflammatory diseases, autoimmune diseases, diabetic retinopathy) and metabolic diseases. Novel small molecules are provided that inhibit one or more of mTORC1, mTORC2, and PI3K-related proteins. Novel methods of providing soluble mTORC1 and mTORC2 complexes are discussed, as well as methods of using the soluble complexes in a high-throughput manner to screen for inhibitory compounds.