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Selective PROTAC-mediated degradation of SMARCA2 is efficacious in SMARCA4 mutant cancers复制

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J Cantley, X Ye, E Rousseau, T Januario…
Nature …, 2022
nature.com
Abstract The mammalian SWItch/Sucrose Non-Fermentable (SWI/SNF) helicase SMARCA4 is frequently mutated in cancer and inactivation results in a cellular dependence on its paralog, SMARCA2, thus making SMARCA2 an attractive synthetic lethal target. However, published data indicates that achieving a high degree of selective SMARCA2 inhibition is likely essential to afford an acceptable therapeutic index, and realizing this objective is challenging due to the homology with the SMARCA4 paralog. Herein we report the …

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