A novel axis of circKIF4A-miR-637-STAT3 promotes brain metastasis in triple-negative breast cancer.

Among patients with triple-negative breast cancer (TNBC), distant metastasis is the leading cause of death. Our previous studies have shown that TNBC progression is greatly facilitated by circKIF4A, but uncertainty remains regarding its role in TNBC brain metastasis and the molecular mechanism. In this study, we found notable upregulation of circKIF4A in TNBC cell lines and brain metastases.

Development and Verification of a Prognostic Ferroptosis-Related Gene Model in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the subtype with the worst prognosis of breast cancer. Ferroptosis, a novel iron-dependent programmed cell death, has an increasingly important role in tumorigenesis and development. However, there is still a lack of research on the relationship between ferroptosis-related genes and the prognosis of TNBC.

Structure-Based Discovery and Optimization of Furo[3,2-]pyridin-4(5)-one Derivatives as Potent and Second Bromodomain (BD2)-Selective Bromo and Extra Terminal Domain (BET) Inhibitors.

Pan-bromodomain and extra terminal (Pan-BET) inhibitors show profound efficacy but exhibit pharmacology-driven toxicities in clinical trials. The development of domain-selective BET inhibitors to separate efficacy and toxicity is urgently needed. Herein, we report a series of furo[3,2-]pyridin-4(5)-one derivatives as novel BD2-selective BET inhibitors.

Discovery of the First Examples of Threonine Tyrosine Kinase PROTAC Degraders.

The first examples of threonine tyrosine kinase (TTK) PROTACs were designed and synthesized. Two of the most potent molecules, and , demonstrated strong TTK degradation in COLO-205 human colorectal cancer cells with DC values of 1.7 and 3.

Identification and optimization of new dual inhibitors of B-Raf and epidermal growth factor receptor kinases for overcoming resistance against vemurafenib.

Epidermal growth factor receptor (EGFR) amplification has been demonstrated to be critical for the inherent and/or acquired resistance against current B-Raf(V600E) inhibitor therapy for melanoma and colorectal cancer patients. We describe the discovery and structure-activity relationship study of a series of 1H-pyrazolo[3,4-b]pyridine-5-carboxamide analogues as novel dual inhibitors of EGFR and B-Raf(V600E) mutant. One of the most promising compounds, 6a, potently inhibited both of the kinases with IC50 values of 8.