Development of 5-hydroxypyrazole derivatives as reversible inhibitors of lysine specific demethylase 1
| Autor: | Alison E. McGonagle, Daniel P. Mould, Tim C. P. Somervaille, Ulf Bremberg, Helen F. Small, Matthis Geitmann, Allan M. Jordan, Donald J. Ogilvie, Alba Maiques-Diaz |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
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 |
| Zdroj: | Mould, D P, Bremberg, U, Jordan, A M, Geitmann, M, Maiques-Diaz, A, McGonagle, A E, Small, H F, Somervaille, T C P & Ogilvie, D 2017, ' Development of 5-hydroxypyrazole derivatives as reversible inhibitors of lysine specific demethylase 1 ', Bioorganic and Medicinal Chemistry Letters, vol. 27, no. 14, pp. 3190-3195 . https://doi.org/10.1016/j.bmcl.2017.05.018 |
| DOI: | 10.1016/j.bmcl.2017.05.018 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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