Design, synthesis, and evaluation of BCL-2 targeting PROTACs.

BCL-2, a member of the BCL-2 protein family, is an antiapoptotic factor that regulates the intrinsic pathway of apoptosis. Due to its aberrant activity, it is frequently implicated in haematopoietic cancers and represents an attractive target for the development of therapeutics that antagonize its activity. A selective BCL-2 inhibitor, venetoclax, was approved for treating chronic lymphocytic leukaemia, acute myeloid leukemia, and other hematologic malignancies, validating BCL-2 as an anticancer target. Since then, alternative therapeutic approaches to modulate the activity of BCL-2 have been explored, such as antibody-drug conjugates and proteolysis-targeting chimeras. Despite numerous research groups focusing on developing degraders of BCL-2 family member proteins, selective BCL-2 PROTACs remain elusive, as disclosed compounds only show dual BCL-xL/BCL-2 degradation. Herein, we report our efforts to develop BCL-2 degraders by incorporating two BCL-2 binding moieties into chimeric compounds that aim to hijack one of three E3 ligases: CRBN, VHL, and IAPs. Even though our project did not result in obtaining a potent and selective BCL-2 PROTAC, our research will aid in understanding the narrow chemical space of BCL-2 degraders.

Factors Contributing to School Effectiveness: A Systematic Literature Review.

This paper aims to provide a systematic review of the literature on school effectiveness, with a focus on identifying the main factors that contribute to successful educational outcomes. The research question that this paper aimed to address is "what are the main factors of school effectiveness?". We were interested in several descriptors such as school, effectiveness/efficiency theories, effectiveness/efficiency research and factors. Studies (published within the 2016-2022 period) were retrieved through two databases: JSTOR and ERIC. This paper defines several categories identified by school effectiveness research. Within these categories, various factors that affect the students' outcomes and the defined effectiveness in school are listed. As the results show, the issue of school effectiveness is multifaceted, as the effectiveness of schools is a complex concept that can be measured through various indicators such as academic achievement, student engagement and teacher satisfaction. The review of school effectiveness revealed that several factors contribute to effective schools, such as strong leadership, effective teaching practices, a positive school culture and parental involvement. Additionally, school resources, such as funding and facilities, can impact school effectiveness, particularly in under-resourced communities.