Anticancer Effects of I-BET151, an Inhibitor of Bromodomain and Extra-Terminal Domain Proteins

I-BET151 is an inhibitor of bromodomain and extra-terminal domain (BET) proteins that selectively inhibits BET family members (BRD2, BRD3, BRD4, and BRDT). Over the past ten years, many studies have demonstrated the potential of I-BET151 in cancer treatment. Specifically, I-BET151 causes cell cycle arrest and inhibits tumor cell proliferation in some hematological malignancies and solid tumors, such as breast cancer, glioma, melanoma, neuroblastoma, and ovarian cancer. The anticancer activity of I-BET151 is related to its effects on NF-κB, Notch, and Hedgehog signal transduction pathway, tumor microenvironment (TME) and telomere elongation. Remarkably, the combination of I-BET151 with select anticancer drugs can partially alleviate the occurrence of drug resistance in chemotherapy. Especially, the combination of forskolin, ISX9, CHIR99021, I-BET151 and DAPT allows GBM cells to be reprogrammed into neurons, and this process does not experience an intermediate pluripotent state. The research on the anticancer mechanism of I-BET151 will lead to new treatment strategies for clinical cancer.

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Expression and significance of the Hedgehog signal transduction pathway in oxygen-induced retinal neovascularization in mice

Drug Design Development and Therapy ◽

10.2147/dddt.s149594 ◽

2018 ◽

Vol Volume 12 ◽

pp. 1337-1346

Author(s):

Meilin Liu ◽

Xiaolong Chen ◽

Henan Liu ◽

Yu Di

Keyword(s):

Signal Transduction ◽

Signal Transduction Pathway ◽

Retinal Neovascularization ◽

Transduction Pathway ◽

Hedgehog Signal Transduction ◽

Hedgehog Signal

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Structural insight into the recognition between Sufu and fused in the Hedgehog signal transduction pathway

Journal of Structural Biology ◽

10.1016/j.jsb.2020.107614 ◽

2020 ◽

Vol 212 (2) ◽

pp. 107614

Author(s):

Hua Li ◽

Wen Wang ◽

Wei Zhang ◽

Geng Wu

Keyword(s):

Signal Transduction ◽

Signal Transduction Pathway ◽

Transduction Pathway ◽

Structural Insight ◽

Hedgehog Signal Transduction ◽

Insight Into ◽

Hedgehog Signal

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Epigenetic Changes in Malignant Uveal Melanoma and Possibilities of Their Therapeutic Targeting

Czech and Slovak Ophthalmology ◽

10.31348/2020/12 ◽

2020 ◽

Vol 76 (2) ◽

pp. 103-110

Author(s):

Božena Smolková ◽

Lucia Demková

Keyword(s):

Uveal Melanoma ◽

Histone Deacetylase Inhibitors ◽

Treatment Strategies ◽

Epigenetic Changes ◽

Cycle Arrest ◽

Risk Patients ◽

New Treatment ◽

Malignant Uveal Melanoma ◽

Traditional Approaches ◽

Effective Drugs

Uveal melanoma (UM) is a deadly cancer that leads to metastatic disease in more than 50 % of the patients. Despite the improvement in the treatment of primary disease, there is still no effective therapy to prevent the development of metastases. Therefore, the disease requires intensive research to identify new treatment strategies. In preclinical UM models, epigenetic drugs have been shown to increase the sensitivity of resistant tumour cells to treatment. The successful use of histone deacetylase inhibitors, which induced cell cycle arrest, reprogramming consistent with melanocyte differentiation and inhibition of tumour growth in preclinical models, demonstrates the role of epigenetic regulation in UM metastasis. Identification of epigenetic changes associated with UM development an progression could contribute to the discovery of more effective drugs that, in combination with traditional approaches, may yield better therapeutic results for high-risk patients.

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