Histone deacetylases (HDACs) play important roles in cell growth, cell differentiation, cell apoptosis, and many other cellular processes. The inhibition of different classes of HDACs has been shown to be closely related to the therapy of cancers and other diseases. In this study, a series of novel CRBN-recruiting HDAC PROTACs were designed and synthesized by linking hydroxamic acid and benzamide with lenalidomide, pomalidomide, and CC-220 through linkers of different lengths and types. One of these PROTACs, denoted 21a, with a new benzyl alcohol linker, exhibited comparably excellent HDAC inhibition activity on different HDAC classes, acceptable degradative activity, and even better in vitro anti-proliferative activities on the MM.1S cell line compared with SAHA. Moreover, we report for the first time the benzyl alcohol linker, which could also offer the potential to be used to develop more types of potent PROTACs for targeting more proteins of interest (POI).

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Background：Keratin 17 expression has been detected in some carcinoma types, although its function in endometrial carcinoma remains unclear. According to the Cancer Genome Atlas (TCGA) data library, we aimed to demonstrate the correlation between Keratin 17 and endometrial carcinoma. Methods：We analyzed the relationship between clinicopathologic characteristics and Keratin 17 expression using Kruskal-Wallis test, Wilcoxon signed-rank test, and Logistic regression. Based on the receiver operating characteristic (ROC) curve and Area Under the Curve (AUC) score, the binary classifier value for Keratin 17 was derived. Kaplan-Meier method and Cox regression analysis were used to assess the prognosis factors. The Keratin 17 Gene set enrichment analysis (GSEA) and immune invasion analysis were used to determine its important functions. Results：Keratin17 expression was associated with the clinical classification of endometrial carcinoma (P=0.002), Histological type (P<0.001). The Keratin 17 ROC curve showed strong diagnostic and prognostic capabilities (AUC=0.789). High Keratin 17 expression indicated a poorer overall survival (OS) (P=0.018). According to immune invasion analysis, the expression of Keratin 17 is associated with some types of immune invasive cells. Conclusions：Keratin 17 expression is strongly associated with poor survival and immune invasion of endometrial carcinoma, and may represent a promising biomarker for endometrial cancer.