14213-01-5Relevant articles and documents
Small Molecule Inhibition of MicroRNA miR-21 Rescues Chemosensitivity of Renal-Cell Carcinoma to Topotecan
Naro, Yuta,Ankenbruck, Nicholas,Thomas, Meryl,Tivon, Yaniv,Connelly, Colleen M.,Gardner, Laura,Deiters, Alexander
, p. 5900 - 5909 (2018/08/04)
Chemical probes of microRNA (miRNA) function are potential tools for understanding miRNA biology that also provide new approaches for discovering therapeutics for miRNA-associated diseases. MicroRNA-21 (miR-21) is an oncogenic miRNA that is overexpressed in most cancers and has been strongly associated with driving chemoresistance in cancers such as renal cell carcinoma (RCC). Using a cell-based luciferase reporter assay to screen small molecules, we identified a novel inhibitor of miR-21 function. Following structure-activity relationship studies, an optimized lead compound demonstrated cytotoxicity in several cancer cell lines. In a chemoresistant-RCC cell line, inhibition of miR-21 via small molecule treatment rescued the expression of tumor-suppressor proteins and sensitized cells to topotecan-induced apoptosis. This resulted in a >10-fold improvement in topotecan activity in cell viability and clonogenic assays. Overall, this work reports a novel small molecule inhibitor for perturbing miR-21 function and demonstrates an approach to enhancing the potency of chemotherapeutics specifically for cancers derived from oncomir addiction.
Click reaction as a tool to combine pharmacophores: The case of Vismodegib
Christodoulou, Michael S.,Mori, Mattia,Pantano, Rebecca,Alfonsi, Romina,Infante, Paola,Botta, Maurizio,Damia, Giovanna,Ricci, Francesca,Sotiropoulou, Panagiota A.,Liekens, Sandra,Botta, Bruno,Passarella, Daniele
, p. 938 - 943 (2015/06/08)
Abstract The design and the preparation of a small library of 1,4-diphenyl-1,2,3-triazole derivatives is reported, with the aim to obtain a new class of Hedgehog pathway inhibitors. The smoothened protein is part of the hedgehog signaling pathway that is
1-Phenyl-4-benzoyl-1H-1,2,3-triazoles as orally bioavailable transcriptional function suppressors of Estrogen-related receptor α
Xu, Shilin,Zhuang, Xiaoxi,Pan, Xiaofen,Zhang, Zhang,Duan, Lei,Liu, Yingxue,Zhang, Lianwen,Ren, Xiaomei,Ding, Ke
, p. 4631 - 4640 (2013/07/19)
Estrogen-related receptor α is a potential candidate target for therapeutic treatment of breast cancer. We describe the discovery and structure-activity relationship study of a series of 1-phenyl-4-benzoyl-1H-1,2, 3-triazoles as novel suppressors of ERRα
Copper(II)-catalyzed conversion of aryl/heteroaryl boronic acids, boronates, and trifluoroborates into the corresponding azides: Substrate scope and limitations
Grimes, Kimberly D.,Gupte, Amol,Aldrich, Courtney C.
experimental part, p. 1441 - 1448 (2010/10/03)
We report the copper(II)-catalyzed conversion of organoboron compounds into the corresponding azide derivatives. A systematic series of phenylboronic acid derivatives is evaluated to examine the importance of steric and electronic effects of the sub-stituents on reaction yield as well as functional group compatibility. Heterocyclic substrates are also shown to participate in this mild reaction while compounds incorporating B-C(sp3) bonds are unreactive under the reaction conditions. The copper(II)-catalyzed boronic acid-azide coupling reaction is further extended to both boronate esters and potassium organotrifluoroborate salts. The method described herein complements existing procedures for the preparation of aryl azides from the respective amino, triazene, and halide derivatives and we expect that it will greatly facilitate copper- and ruthenium-catalyzed azide-alkyne cycloaddition reactions for the preparation of diversely functionalized 1-aryl- or 1-heteroaryl-1,2,3- triazoles derivatives. Georg Thieme Verlag Stuttgart.
