Discovery of EEDi-5273 as an Exceptionally Potent and Orally Efficacious EED Inhibitor Capable of Ac
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Engineering topics
Publications and source records attributed to Chen, Jianyong.
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Abstract not provided
Signal transducer and activator of transcription 3 (STAT3) is an attractive cancer therapeutic target. Here we report the discovery of SD-36, a small-molecule degrader of STAT3. SD-36 potently induces the degradation of STAT3 protein in vitro and in vivo and demonstrates high selectivity over other STAT members. Induced degradation of STAT3 results in a strong suppression of its transcription network in leukemia and lymphoma cells. SD-36 inhibits the growth of a subset of acute myeloid leukemia and anaplastic large-cell lymphoma cell lines by inducing cell-cycle arrest and/or apoptosis. SD-36 achieves complete and long-lasting tumor regression in multiple xenograft mouse models at well-tolerated dose schedules. Degradation of STAT3 protein, therefore, is a promising cancer therapeutic strategy.
The electronic properties, lattice vibration, and electron-phonon interaction properties of KBi{sub 2} are studied systematically by first-principles calculations. The agreement of calculated Debye temperature, electron-phonon coupling constant, and transition temperature with latest experiments validates the reliability of our work. Our results provide evidence that the superconducting transition of KBi{sub 2} originates from isotropical coupling of all phonon modes according to isotropical Migdal-Eliashberg theory.
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