1. Development of 5-hydroxypyrazole derivatives as reversible inhibitors of lysine specific demethylase 1
- Author
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Alison E. McGonagle, Daniel P. Mould, Tim C. P. Somervaille, Ulf Bremberg, Helen F. Small, Matthis Geitmann, Allan M. Jordan, Donald J. Ogilvie, and Alba Maiques-Diaz
- Subjects
0301 basic medicine ,animal structures ,Cancer therapy ,Reversible inhibitor ,Clinical Biochemistry ,Patent literature ,Pharmaceutical Science ,LSD1 ,Biochemistry ,Acute myeloid leukaemia ,Cell Line ,03 medical and health sciences ,Inhibitory Concentration 50 ,Mice ,Structure-Activity Relationship ,Catalytic Domain ,Drug Discovery ,Animals ,Humans ,Surface plasmon resonance ,Molecular Biology ,IC50 ,Histone Demethylases ,Binding Sites ,Manchester Cancer Research Centre ,Chemistry ,Epigenetic therapy ,ResearchInstitutes_Networks_Beacons/mcrc ,Organic Chemistry ,Rational design ,KDM1A ,Cell Differentiation ,Surface Plasmon Resonance ,Combinatorial chemistry ,Molecular Docking Simulation ,030104 developmental biology ,Stem cell differentiation ,Molecular Medicine ,Pyrazoles ,Epigenetics ,B7-2 Antigen ,LYSINE-SPECIFIC DEMETHYLASE 1 ,Half-Life - Abstract
A series of reversible inhibitors of lysine specific demethylase 1 (LSD1) with a 5-hydroxypyrazole scaffold have been developed from compound 7, which was identified from the patent literature. Surface plasmon resonance (SPR) and biochemical analysis showed it to be a reversible LSD1 inhibitor with an IC50 value of 0.23 µM. Optimisation of this compound by rational design afforded compounds with Kd values of
- Published
- 2017
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