943-45-3Relevant articles and documents
Exploration of a 14-3-3 PPI Pocket by Covalent Fragments as Stabilizers
Sijbesma, Eline,Hallenbeck, Kenneth K.,Andrei, Sebastian A.,Rust, Reanne R.,Adriaans, Joris M. C.,Brunsveld, Luc,Arkin, Michelle R.,Ottmann, Christian
supporting information, p. 976 - 982 (2021/05/27)
The systematic discovery of functional fragments binding to the composite interface of protein complexes is a first critical step for the development of orthosteric stabilizers of protein-protein interactions (PPIs). We have previously shown that disulfide trapping successfully yielded covalent stabilizers for the PPI of 14-3-3 with the estrogen receptor ERα. Here we provide an assessment of the composite PPI target pocket and the molecular characteristics of various fragments binding to a specific subpocket. Evaluating structure-activity relationships highlights the basic principles for PPI stabilization by these covalent fragments that engage a relatively large and exposed binding pocket at the protein/peptide interface with a "molecular glue"mode of action.
PRMT5 INHIBITORS AND USES THEREOF
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Paragraph 0300-0301, (2019/04/05)
Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.
PRMT5 INHIBITORS CONTAINING A DIHYDRO- OR TETRAHYDROISOQUINOLINE AND USES THEREOF
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Paragraph 00289, (2014/07/08)
Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5- mediated disorders are also described.