286837-12-5Relevant articles and documents
IMIDAZOPYRIMIDINES AS EED INHIBITORS AND THE USE THEREOF
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Paragraph 0445; 0446, (2021/02/12)
The present disclosure provides compounds represented by Formula (I) wherein R1, R2, R3, and R4 are as defined in the specification, and the salts and solvates thereof. Compounds of Formula (I) are FED inhibitors. FED inhibitors are useful for the treatment of cancer and other diseases.
Discovery of EEDi-5273 as an Exceptionally Potent and Orally Efficacious EED Inhibitor Capable of Achieving Complete and Persistent Tumor Regression
Chen, Jianyong,Chinnaswamy, Krishnapriya,Li, Ruiting,Lu, Jianfeng,McEachern, Donna,Petrunak, Elyse,Rej, Rohan Kalyan,Stuckey, Jeanne A.,Sun, Duxin,Tang, Guozhi,Wang, Changwei,Wang, Lu,Wang, Mi,Wang, Shaomeng,Wen, Bo,Yang, Chao-Yie,Zawacki, Kaitlin P.,Zhou, Yunlong
, p. 14540 - 14556 (2021/10/26)
Embryonic ectoderm development (EED) is a promising therapeutic target for human cancers and other diseases. We report herein the discovery of exceptionally potent and efficacious EED inhibitors. By conformational restriction of a previously reported EED
EEDi-5285: An Exceptionally Potent, Efficacious, and Orally Active Small-Molecule Inhibitor of Embryonic Ectoderm Development
Rej, Rohan Kalyan,Wang, Changwei,Lu, Jianfeng,Wang, Mi,Petrunak, Elyse,Zawacki, Kaitlin P.,McEachern, Donna,Fernandez-Salas, Ester,Yang, Chao-Yie,Wang, Lu,Li, Ruiting,Chinnaswamy, Krishnapriya,Wen, Bo,Sun, Duxin,Stuckey, Jeanne,Zhou, Yunlong,Chen, Jianyong,Tang, Guozhi,Wang, Shaomeng
, p. 7252 - 7267 (2020/07/14)
Inhibition of embryonic ectoderm development (EED) is a new cancer therapeutic strategy. Herein, we report our discovery of EEDi-5285 as an exceptionally potent, efficacious, and orally active EED inhibitor. EEDi-5285 binds to the EED protein with an IC50 value of 0.2 nM and inhibits cell growth with IC50 values of 20 pM and 0.5 nM in the Pfeiffer and KARPAS422 lymphoma cell lines, respectively, carrying an EZH2 mutation. EEDi-5285 is approximately 100 times more potent than EED226 in binding to EED and >300 times more potent than EED226 in inhibition of cell growth in the KARPAS422 cell line. EEDi-5285 has excellent pharmacokinetics and achieves complete and durable tumor regression in the KARPAS422 xenograft model in mice with oral administration. The cocrystal structure of EEDi-5285 in a complex with EED defines the precise structural basis for their high binding affinity. EEDi-5285 is the most potent and efficacious EED inhibitor reported to date.
