title: [Mechanism of A New DOT1L Inhibitor EPZ-5676 and Its Research Progress -Review].
abstract: Leukemia carring translocation at the 11q23 locus is referred to MLL-rearranged (MLL-r) leukemia, and the occurrence of this genetic lesion is associated with a poor prognosis. The most common translocation chromosomes are chromosomes 4,9 and 10. Recently MLL protein was found to interact with DOT1L (DOT1-like) protein, which can promote leukemogenesis. A new DOT1L inhibitor EPZ-5676 can selectively inhibit proliferation, promote apoptosis and differentiation, which was also found to act synergistically with anti-AML (acute myeloid leukemia) and anti-ALL (acute lymphoblastic leukemia) drugs. EPZ-5676 can also induce sustained regression in a rat xenograft model of MLL-rearranged leukemia. Now the novel drug is in phase I of clinical trail. The results suggest that the EPZ-5676 is promising. In this article, the mechanism of EPZ-5676 and its research progress are reviwed.
authors.affiliation: Department of Hematology,Peking University Third Hospital, Beijing 100191,China.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Li
authors.affiliation: Department of Hematology,Peking University Third Hospital, Beijing 100191,China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Hematology,Peking University Third Hospital, Beijing 100191,China. E-mail: xykbysy@ 163. com.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Ke
mesh_terms: D000818:Animals; D017209:Apoptosis; D001562:Benzimidazoles / Q000627:therapeutic use*; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D015470:Leukemia, Myeloid, Acute; D008780:Methyltransferases; D051788:Myeloid-Lymphoid Leukemia Protein; D014178:Translocation, Genetic
chemical_list: D001562:Benzimidazoles; C583893:EPZ-5676; C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; C473477:DOT1L protein, human; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase