- Small Molecule Inhibition of MicroRNA miR-21 Rescues Chemosensitivity of Renal-Cell Carcinoma to Topotecan
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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.
- Naro, Yuta,Ankenbruck, Nicholas,Thomas, Meryl,Tivon, Yaniv,Connelly, Colleen M.,Gardner, Laura,Deiters, Alexander
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p. 5900 - 5909
(2018/08/04)
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- Synthesis of new 1,2,3-triazolo[1,5-a]quinazolinones
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(Chemical Equation Presented) Synthesis of novel 3-substituted-1,2,3- triazolo[1,5-a]quinazolinones in high yields was performed via anionic hetero-domino reaction of appropriate substituted 2-azidobenzoates prepared from isatines and acetonitriles activated by 1,3-thiazole, 1,3-benzothiazole, 1,3,4-oxadiazole, and 1,2,4-oxadiazole rings. It was shown that acetonitriles exhibited high reactivity and were convenient methylenic compounds for such reactions providing rapid structural variation.
- Pokhodylo, Nazariy T.,Matiychuk, Vasyl S.
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experimental part
p. 415 - 420
(2010/06/16)
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- Synthesis of 5-hydroxymethyl-8-methyl-3-(3-aryl-[1,2,4]oxadiazol-5-yl)-2h- pyrano[2,3-c]pyridin-2-ones and their esters
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New 5-hydroxymethyl-8-methyl-3-(3-aryl-[1,2,4]oxadiazol-5-yl)-2H-pyrano-[2, 3-c]pyridin-2-ones and their esters were synthesized. The structure of obtained compounds was determined through a complete 1H NMR analysis. Copyright Taylor & Francis Group, LLC.
- Zhuravel, Irina O.,Kovalenko, Sergiy M.,Zaremba, Oleg V.,Detistov, Oleksandr S.,Kovalenko, Svitlana S.,Chernykh, Valentin P.
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p. 3778 - 3784
(2008/12/23)
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- Chemistry of 1,3-Oxazine-6-thiones. Ring Transformation
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Two 1,3-oxazine-6-thione derivatives obtained by "S,N-Double Rearrangement" reacted with several nucleophiles to produce 1,3-diazin-6-ones, 6-imino-1,3-oxazines, 1,3,4-triazoles, 1,2,4-oxadiazoles, and 1,3-thiazol-6-ones.Their ring transformations are dis
- Yokoyama, Masataka,Inazawa, Hiroshi,Shimizu, Tomoji,Kodera, Masahito,Imamoto, Tsuneo
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p. 187 - 194
(2007/10/02)
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