ArticleOncotarget2015
Systems biology network-based discovery of a small molecule activator BL-AD008 targeting AMPK/ZIPK and inducing apoptosis in cervical cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 33 citations in OpenAlex.
- Deep learning identification of novel autophagic protein-protein interactions and experimental validation of Beclin 2-Ubiquilin 1 axis in triple-negative breast cancer.Oncology research · 2025Article
- Anomanolide C suppresses tumor progression and metastasis by ubiquitinating GPX4-driven autophagy-dependent ferroptosis in triple negative breast cancer.International journal of biological sciences · 2023Article
- EID3 Promotes Glioma Cell Proliferation and Survival by Inactivating AMPKα1.Journal of Korean Neurosurgical Society · 2022Article
- Systems biology approaches based discovery of a small molecule inhibitor targeting both c-Met/PARP-1 and inducing cell death in breast cancer.Journal of Cancer · 2020Article
- 3'-epi-12β-hydroxyfroside, a new cardenolide, induces cytoprotective autophagy via blocking the Hsp90/Akt/mTOR axis in lung cancer cells.Theranostics · 2018Article
- Targeting energy metabolism to eliminate cancer cells.Cancer management and research · 2018Review
- Discovery of a small molecule targeting ULK1-modulated cell death of triple negative breast cancerChemical science · 2017Article
- Crystal structure-based discovery of a novel synthesized PARP1 inhibitor (OL-1) with apoptosis-inducing mechanisms in triple-negative breast cancer.Scientific reports · 2016Article
- Identification of polycystic ovary syndrome potential drug targets based on pathobiological similarity in the protein-protein interaction network.Oncotarget · 2016Article
- Penicimenolides A-F, Resorcylic Acid Lactones from Penicillium sp., isolated from the Rhizosphere Soil of Panax notoginseng.Scientific reports · 2016Article
- Synonymous mutations in oncogenesis and apoptosis versus survival unveiled by network modeling.Oncotarget · 2016Article
- Hernandezine, a novel AMPK activator induces autophagic cell death in drug-resistant cancers.Oncotarget · 2016Article
- Identification of Novel Pathways in Plant Lectin-Induced Cancer Cell Apoptosis.International journal of molecular sciences · 2016Article
- Non-muscle myosin II in disease: mechanisms and therapeutic opportunities.Disease models & mechanisms · 2015Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aim of this study was to discover a small molecule activator BL-AD008 targeting AMPK/ZIPK and inducing apoptosis in cervical cancer. In this study, we systematically constructed the global protein-protein interaction (PPI) network and predicted apoptosis-related protein connections by the Naïve Bayesian model. Then, we identified some classical apoptotic PPIs and other previously unrecognized PPIs between apoptotic kinases, such as AMPK and ZIPK. Subsequently, we screened a series of candidate compounds targeting AMPK/ZIPK, synthesized some compounds and eventually discovered a novel dual-target activator (BL-AD008). Moreover, we found BL-AD008 bear remarkable anti-proliferative activities toward cervical cancer cells and could induce apoptosis by death-receptor and mitochondrial pathways. Additionally, we found that BL-AD008-induced apoptosis was affected by the combination of AMPK and ZIPK. Then, we found that BL-AD008 bear its anti-tumor activities and induced apoptosis by targeting AMPK/ZIPK in vivo. In conclusion, these results demonstrate the ability of systems biology network to identify some key apoptotic kinase targets AMPK and ZIPK; thus providing a dual-target small molecule activator (BL-AD008) as a potential new apoptosis-modulating drug in future cervical cancer therapy.
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