Apoptosis is the major mode of programmed cell death, which conduces to maintain tissue homeostasis, clearance of abnormal cells and development of organisms. Over the past two decades, great progress and significant clinical benefits in cancer treatment have been made by targeting Bcl-2 anti-apoptotic proteins. However, with the deep research of clinic, the therapeutic value of single target inhibitors is restricted due to the limited monotherapy activity, potential and complex drug resistance as well as monotherapy safety. This review focuses on recent advance in discovery of novel apoptosis inducers targeting Bcl-2 anti-apoptotic proteins aiming to overcome existing therapeutic limitations, and introduce the strategies and advanced technologies in the drug design and optimization.
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http://dx.doi.org/10.1016/j.ejmech.2022.114184 | DOI Listing |
Front Pharmacol
January 2025
Department of Pharmacognosy, School of Pharmacy, Xinjiang Medical University, Urumqi, China.
Objective: To elucidate the metabolic mechanisms by which acteoside (ACT) isolated from alleviates cancer-related fatigue (CRF) in a murine model of colon cancer with cachexia.
Methods: BALB/c mice inoculated with C26 colon cancer cells were treated with paclitaxel (PTX, 10 mg/kg) and ACT (100 mg/kg) alone or in combination for 21 days. Fatigue-associated behaviors, tumor inhibition rate, and skeletal muscle morphology assessed by hematoxylin-eosin (H&E) staining and electron microscopy were evaluated.
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Physiology, College of Medicine, King Saud University, 12271, Riyadh, Saudi Arabia.
Ischemia-reperfusion injury (IRI) is a common pathogenic situation that arises throughout all liver surgeries, including liver transplants. We aimed to compare the preventive effects of valsartan (VST) against valsartan + sacubitril (LCZ696) on hepatic injury caused by IRI. A total of thirty-six male Westar albino rats were split into six groups randomly: sham, IRI, VST + IRI, LCZ696 + IRI, VST, and LCZ696.
View Article and Find Full Text PDFMol Carcinog
January 2025
Institute of Precision Medicine, The First Affiliated Hospital; Department of Pediatrics, The Seventh Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Acute myeloid leukemia (AML) is marked by the proliferation of abnormal myeloid progenitor cells in the bone marrow and blood, leading to low cure rates despite new drug approvals from 2017 to 2018. Current therapies often fail due to the emergence of drug resistance mechanisms, such as those involving anti-apoptotic pathways and immune evasion, highlighting an urgent need for novel approaches to overcome these limitations. Programmed cell death (PCD) is crucial for tissue homeostasis, with PANoptosis-a form of PCD integrating pyroptosis, apoptosis, and necroptosis-recently identified.
View Article and Find Full Text PDFBioorg Chem
January 2025
Department of Chemistry, Faculty of Science, Al-Azhar University, Cairo 11754 Egypt.
The vascular endothelial growth factor receptor is essential for the angiogenesis of cancer. Tumor propagation was effectively suppressed by inhibiting VEGFR-2 activity. As a result, the target quinoxaline-pyrazole hybrids were created in a way that closely resembled the structural characteristics of VEGFR-2 inhibitors.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address:
Callistephus chinensis Nees is an herbaceous plant in the Asteraceae family that has various traditional effects, especially in preventing liver disease. Callistephus A (CA) is a sesquiterpene compound with a rare 6/7 ring skeleton, which has been isolated only from the Callistephus chinensis Nees, but whether CA protects the liver is unknown. Immunological liver injury (ILI) is a common liver disease mediated by the immune system.
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