Reference of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleIn 2022 ,《Fragment-Based Discovery of MRTX1719, a Synthetic Lethal Inhibitor of the PRMT5•MTA Complex for the Treatment of MTAP-Deleted Cancers》 appeared in Journal of Medicinal Chemistry. The author of the article were Smith, Christopher R.; Aranda, Ruth; Bobinski, Thomas P.; Briere, David M.; Burns, Aaron C.; Christensen, James G.; Clarine, Jeffery; Engstrom, Lars D.; Gunn, Robin J.; Ivetac, Anthony; Jean-Baptiste, Ronald; Ketcham, John M.; Kobayashi, Masakazu; Kuehler, Jon; Kulyk, Svitlana; Lawson, J. David; Moya, Krystal; Olson, Peter; Rahbaek, Lisa; Thomas, Nicole C.; Wang, Xiaolun; Waters, Laura M.; Marx, Matthew A.. The article conveys some information:
The PRMT5•MTA complex has recently emerged as a new synthetically lethal drug target for the treatment of MTAP-deleted cancers. Here, we report the discovery of development candidate MRTX1719. MRTX1719 is a potent and selective binder to the PRMT5•MTA complex and selectively inhibits PRMT5 activity in MTAP-deleted cells compared to MTAP-wild-type cells. Daily oral administration of MRTX1719 to tumor xenograft-bearing mice demonstrated dose-dependent inhibition of PRMT5-dependent sym. dimethylarginine protein modification in MTAP-deleted tumors that correlated with antitumor activity. A 4-(aminomethyl)phthalazin-1(2H)-one hit was identified through a fragment-based screen, followed by x-ray crystallog., to confirm binding to the PRMT5•MTA complex. Fragment growth supported by structural insights from x-ray crystallog. coupled with optimization of pharmacokinetic properties aided the discovery of development candidate MRTX1719. In the experiment, the researchers used many compounds, for example, 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0Reference of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole)
1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. Reference of 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole
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