生物活性

• 描述APE1 is an enzyme that is involve in the DNA base excision repair pathway. Its main role in the repair of damaged or mismatched nucleotides in DNA is to create a nick in the phosphodiester backbone of the AP site created when DNA glycosylase removes the damaged base^[1]. Lucanthone is a novel autophagic inhibitor which also inhibits APE1by direct protein binding without affecting its redox activity. It induces apoptosis via cathepsin D accumulation and enhance histone deacetylase inhibitor-induced cell death in MDA-MB-231 cells. Combined treatment with lucanthone and TRAIL significantly induced apoptosis in human renal carcinoma, prostate carcinoma and lung carcinoma cells^[2]. Lucanthone reduces cell viability to a similar extent in a panel of seven breast cancer cell lines. In addition, a direct comparison reveals that Lucanthone is significantly more potent than Chloroquine (CQ) at reducing breast cancer cell viability with a mean IC50 of 7.2 μM versus 66 μM for CQ^[3].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02014545	Brain Metastases ... more >> Non-small Cell Lung Cancer Collapse <<	Phase 2	Withdrawn(Pending resolution o... more >>f study drug issues) Collapse <<	-	United States, North Carolina ... more >> Comprehensive Cancer Center of Wake Forest University Winston-Salem, North Carolina, United States, 27157 Collapse <<
  NCT01587144	Glioblastoma Multiforme	Phase 2	Terminated(Sponsor's decision)	-	United States, California ... more >> UCSD Moores Cancer Center La Jolla, California, United States, 92093 UCI Medical Center Orange, California, United States, 92868 United States, New York Dent Neurologic Institute Amherst, New York, United States, 14226 United States, Ohio Fairview Hospital Moll Cancer Center/Cleveland Clinic Cleveland, Ohio, United States, 44111 Cleveland Clinic Cleveland, Ohio, United States, 44195 Hillcrest Hospital Hirsh Cancer Center/Cleveland Clinic Mayfield, Ohio, United States, 44124 India Gujarat Cancer Research Institute Ahmedabad, Gujarat, India, 380016 Jaslok Hospital & Research Centre Mumbai, Maharashtra, India, 400062 Bhagwan Mahaveer Cancer Hospital & Reseach Centre Jaipur, Rajasthan, India, 302017 Chittaranjan National Cancer Institute Kolkata, West Bengal, India, 700026 Collapse <<

• 参考文献

• [1] Whitaker AM, Freudenthal BD. APE1: A skilled nucleic acid surgeon. DNA Repair (Amst). 2018 Nov;71:93-100.

  [2] Yoon JY, Woo SM, Seo SU, Song SR, Lee SG, Kwon TK. Lucanthone, Autophagy Inhibitor, Enhances the Apoptotic Effects of TRAIL through miR-216a-5p-Mediated DR5 Upregulation and DUB3-Mediated Mcl-1 Downregulation. Int J Mol Sci. 2021 Dec 21;23(1):17.

  [3] Carew JS, Espitia CM, Esquivel JA 2nd, Mahalingam D, Kelly KR, Reddy G, Giles FJ, Nawrocki ST. Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.