Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors was written by Yu, Wenyu;Chory, Emma J.;Wernimont, Amy K.;Tempel, Wolfram;Scopton, Alex;Federation, Alexander;Marineau, Jason J.;Qi, Jun;Barsyte-Lovejoy, Dalia;Yi, Joanna;Marcellus, Richard;Iacob, Roxana E.;Engen, John R.;Griffin, Carly;Aman, Ahmed;Wienholds, Erno;Li, Fengling;Pineda, Javier;Estiu, Guillermina;Shatseva, Tatiana;Hajian, Taraneh;Al-awar, Rima;Dick, John E.;Vedadi, Masoud;Brown, Peter J.;Arrowsmith, Cheryl H.;Bradner, James E.;Schapira, Matthieu. And the article was included in Nature Communications in 2012.SDS of cas: 158078-04-7 The following contents are mentioned in the article:
Selective inhibition of protein methyltransferases is a promising new approach to drug discovery. An attractive strategy towards this goal is the development of compounds that selectively inhibit binding of the cofactor, S-adenosylmethionine, within specific protein methyltransferases. Here we report the three-dimensional structure of the protein methyltransferase DOT1L bound to EPZ004777, the first S-adenosylmethionine-competitive inhibitor of a protein methyltransferase with in vivo efficacy. This structure and those of four new analogs reveal remodelling of the catalytic site. EPZ004777 and a brominated analog, SGC0946, inhibit DOT1L in vitro and selectively kill mixed lineage leukemia cells, in which DOT1L is aberrantly localized via interaction with an oncogenic MLL fusion protein. These data provide important new insight into mechanisms of cell-active S-adenosylmethionine-competitive protein methyltransferase inhibitors, and establish a foundation for the further development of drug-like inhibitors of DOT1L for cancer therapy. This study involved multiple reactions and reactants, such as ((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (cas: 158078-04-7SDS of cas: 158078-04-7).
((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (cas: 158078-04-7) belongs to dioxole derivatives. Dioxoles, particularly fluorinated dioxoles, are used as co-monomers to make polymers that find use in forming protective coatings for chemical resistance. Dioxole functionalized metal-organic frameworks have also been recently reported.SDS of cas: 158078-04-7
Referemce:
1,3-Benzodioxole – Wikipedia,
Dioxole | C3H4O2 – PubChem