111627-46-4Relevant articles and documents
Design of the First-in-Class, Highly Potent Irreversible Inhibitor Targeting the Menin-MLL Protein–Protein Interaction
Xu, Shilin,Aguilar, Angelo,Xu, Tianfeng,Zheng, Ke,Huang, Liyue,Stuckey, Jeanne,Chinnaswamy, Krishnapriya,Bernard, Denzil,Fernández-Salas, Ester,Liu, Liu,Wang, Mi,McEachern, Donna,Przybranowski, Sally,Foster, Caroline,Wang, Shaomeng
supporting information, p. 1601 - 1605 (2018/01/22)
The structure-based design of M-525 as the first-in-class, highly potent, irreversible small-molecule inhibitor of the menin-MLL interaction is presented. M-525 targets cellular menin protein at sub-nanomolar concentrations and achieves low nanomolar potencies in cell growth inhibition and in the suppression of MLL-regulated gene expression in MLL leukemia cells. M-525 demonstrates high cellular specificity over non-MLL leukemia cells and is more than 30 times more potent than its corresponding reversible inhibitors. Mass spectrometric analysis and co-crystal structure of M-525 in complex with menin firmly establish its mode of action. A single administration of M-525 effectively suppresses MLL-regulated gene expression in tumor tissue. An efficient procedure was developed to synthesize M-525. This study demonstrates that irreversible inhibition of menin may be a promising therapeutic strategy for MLL leukemia.
Azabicyclic compounds, a process for their preparation and pharmaceutical compositions containing them.
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Page/Page column 5, (2008/06/13)
A compound selected from those of formula (I): wherein m and n, which may be identical or different, each represent an integer from 0 to 2 inclusive, with the sum of the two integers being from 2 to 3 inclusive, p and q, which may be identical or differen
Arylalkylheterocyclic amines,N-substituted by aryloxyalkyl group in a method for allergy treatment
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, (2008/06/13)
A method of inhibiting Type 1 allergic responses in a living animal body with substituted heterocyclic amines is disclosed wherein the active agents are expressed generally by the formula which includes certain known and certain known compounds: STR1 wherein P is zero, one or two; m is one to six inclusive; A is selected from hydrogen, hydroxy or cyano; d is zero or one; Q is --CH--, CH2 -- or STR2 n is zero or one and when Q is --CH-- and n is one, a double bond is formed with one of the adjacent carbons but not both at the same time, and when n and d are zero at the same time, a double bond is formed between the α carbon and a carbon of the central heterocyclic amine ring; Ar, D and R are selected from phenyl, substituted phenyl, pyridinyl, thienyl, furanyl or naphthyl and in addition, R may have the values benzyl, substituted benzyl, cycloalkyl or loweralkyl and D may additionally have the values: 2H-1-benzopyran-2-one,4-oxo-4H-1-benzopyran-2-carboxylic acid loweralkyl ester, 2,3-dihydro-4H-1-benzopyran-4-one, 1,4-benzodioxanloweralkyl-2-yl or 1,1'-biphenyl-4-yl and the pharmaceutically acceptable salts thereof.