183319-57-5Relevant articles and documents
Pharmacological Targeting of Vacuolar H+-ATPase via Subunit V1G Combats Multidrug-Resistant Cancer
Wang, Yuezhou,Zhang, Lei,Wei, Yanling,Huang, Wei,Li, Li,Wu, An-an,Dastur, Anahita,Greninger, Patricia,Bray, Walter M.,Zhang, Chen-Song,Li, Mengqi,Lian, Wenhua,Hu, Zhiyu,Wang, Xiaoyong,Liu, Gang,Yao, Luming,Guh, Jih-Hwa,Chen, Lanfen,Wang, Hong-Rui,Zhou, Dawang,Lin, Sheng-Cai,Xu, Qingyan,Shen, Yuemao,Zhang, Jianming,Jurica, Melissa S.,Benes, Cyril H.,Deng, Xianming
, p. 1359 - 8,1370 (2020/07/25)
Multidrug resistance (MDR) in cancer remains a major challenge for the success of chemotherapy. Natural products have been a rich source for the discovery of drugs against MDR cancers. Here, we applied high-throughput cytotoxicity screening of an in-house natural product library against MDR SGC7901/VCR cells and identified that the cyclodepsipeptide verucopeptin demonstrated notable antitumor potency. Cytological profiling combined with click chemistry-based proteomics revealed that ATP6V1G directly interacted with verucopeptin. ATP6V1G, a subunit of the vacuolar H+-ATPase (v-ATPase) that has not been previously targeted, was essential for SGC7901/VCR cell growth. Verucopeptin exhibited strong inhibition of both v-ATPase activity and mTORC1 signaling, leading to substantial pharmacological efficacy against SGC7901/VCR cell proliferation and tumor growth in vivo. Our results demonstrate that targeting v-ATPase via its V1G subunit constitutes a unique approach for modulating v-ATPase and mTORC1 signaling with great potential for the development of therapeutics against MDR cancers.Alternative strategy for treating multidrug-resistant (MDR) cancer is needed. Wang et al. show that the natural product verucopeptin kills MDR cancer by targeting the ATP6V1G subunit of v-ATPase, which leads to strong inhibition of both v-ATPase activity and mTORC1 signaling.
NOVEL BIFUNCTIONAL COMPOUNDS WHICH INHIBIT PROTEIN KINASES AND HISTONE DEACETYLASES
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Page/Page column 103, (2009/06/27)
The present invention relates to a bifunctional compound of formula I or its pharmaceutically acceptable salts or solvates A-L-B (I) wherein A is a histone deacetylase (HDAC) inhibitory moiety, L is a single bond or a linker group and B is a protein kinase inhibitory moiety. The bifunctional compound according to formula (I) is useful for the treatment of malignant and non-malignant neoplasia and diseases related to abnormal cell growth
ALKYNYL AND AZIDO-SUBSTITUTED 4-ANILINOQUINAZOLINES
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, (2008/06/13)
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