22231-61-4Relevant articles and documents
Gene editing and synthetically accessible inhibitors reveal role for TPC2 in HCC cell proliferation and tumor growth
Bartel, Karin,Biel, Martin,Bracher, Franz,Chao, Yu-Kai,Chen, Cheng-Chang,Gegenfurtner, Florian A.,Geisslinger, Franz,Gerndt, Susanne,Gerwien, Aaron,Grimm, Christian,Nguyen, Ong Nam Phuong,Ortler, Carina,Schaefer, Michael,Urban, Nicole,Vollmar, Angelika M.,Zahler, Stefan,Zisis, Themistoklis,Müller, Christoph,Müller, Martin
, p. 1119 - 27,1131 (2021/08/19)
The role of two-pore channel 2 (TPC2), one of the few cation channels localized on endolysosomal membranes, in cancer remains poorly understood. Here, we report that TPC2 knockout reduces proliferation of cancer cells in vitro, affects their energy metabolism, and successfully abrogates tumor growth in vivo. Concurrently, we have developed simplified analogs of the alkaloid tetrandrine as potent TPC2 inhibitors by screening a library of synthesized benzyltetrahydroisoquinoline derivatives. Removal of dispensable substructures of the lead molecule tetrandrine increases antiproliferative properties against cancer cells and impairs proangiogenic signaling of endothelial cells to a greater extent than tetrandrine. Simultaneously, toxic effects on non-cancerous cells are reduced, allowing in vivo administration and revealing a TPC2 inhibitor with antitumor efficacy in mice. Hence, our study unveils TPC2 as valid target for cancer therapy and provides easily accessible tetrandrine analogs as a promising option for effective pharmacological interference.
Vanadium-Catalyzed Oxidative Intramolecular Coupling of Tethered Phenols: Formation of Phenol-Dienone Products
Gilmartin, Philip H.,Kozlowski, Marisa C.
supporting information, p. 2914 - 2919 (2020/04/10)
A mild and efficient method for the vanadium-catalyzed intramolecular coupling of tethered free phenols is described. The corresponding phenol-dienone products are prepared directly in good yields with low catalyst loadings. Electronically diverse tethered phenol precursors are well tolerated, and the catalytic method was effectively applied as the key step in syntheses of three natural products and a synthetically useful morphinan alkaloid precursor.
PHENYL [A]INDOLE[2,3-G]QUINOLIZINE COMPOUNDS, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION, AND APPLICATIONS THEREOF
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Paragraph 0099; 0102, (2019/02/13)
The present invention relates to phenyl [a]indole[2,3-g]quinolizine compounds represented by formula (I), a preparation method therefor, a pharmaceutical composition, and applications thereof. Specific applications are applications in the preparation of d
