title: Structure-based screening and optimization of cytisine derivatives as inhibitors of the menin-MLL interaction.
abstract: The natural product-like compound 1 was identified as a direct inhibitor of the menin-MLL interaction by in silico screening. Structure-based optimization furnished analogue 1a, which showed significantly higher potency than both the lead structure 1 and the reference compound MI-2.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. duncanleung@umac.mo.
authors.forename: Hai-Jing
authors.initials: HJ
authors.lastname: Zhong
authors.forename: Bo Ra
authors.initials: BR
authors.lastname: Lee
authors.forename: Joshua William
authors.initials: JW
authors.lastname: Boyle
authors.forename: Wanhe
authors.initials: W
authors.lastname: Wang
authors.forename: Dik-Lung
authors.initials: DL
authors.lastname: Ma
authors.forename: Philip Wai
authors.initials: PW
authors.lastname: Hong Chan
authors.forename: Chung-Hang
authors.initials: CH
authors.lastname: Leung
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001392:Azocines / Q000737:chemistry / Q000494:pharmacology; D056945:Hep G2 Cells; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors*; D006801:Humans; D008958:Models, Molecular; D051788:Myeloid-Lymphoid Leukemia Protein / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D011807:Quinolizines / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D000093843:Quinolizidine Alkaloids
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D001392:Azocines; D011495:Histone-Lysine N-Methyltransferase; D051788:Myeloid-Lymphoid Leukemia Protein; D011518:Proto-Oncogene Proteins; D011807:Quinolizines; C497422:KMT2A protein, human; C105373:MEN1 protein, human; C004712:cytisine; D000093843:Quinolizidine Alkaloids