Yu, Wenyu published the artcileCatalytic site remodelling of the DOT1L methyltransferase by selective inhibitors, Computed Properties of 1338466-77-5, the publication is Nature Communications (2012), 3(Dec.), 2304/1-2304/11, database is CAplus and MEDLINE.
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.
Nature Communications published new progress about 1338466-77-5. 1338466-77-5 belongs to tetrahydrofurans, auxiliary class Epigenetics,Histone Methyltransferase, name is 1-(3-((((2R,3S,4R,5R)-5-(4-Amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)(isopropyl)amino)propyl)-3-(4-(tert-butyl)phenyl)urea, and the molecular formula is C4H10O2, Computed Properties of 1338466-77-5.
Referemce:
https://en.wikipedia.org/wiki/Tetrahydrofuran,
Tetrahydrofuran | (CH2)3CH2O – PubChem