Open AccessSynthesis of HDAC Inhibitor Libraries via Microscale Workflow
Author(s) -
Kevin D. Dykstra,
Eric Streckfuss,
Min Liu,
Jian Liu,
Youg Yu,
Ming Wang,
Joseph A. Kozlowski,
Robert W. Myers,
Alexei V. Buevich,
M. Maletić,
Petr Váchal,
Shane W. Krska
Publication year - 2021
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.0c00596
Subject(s) - workflow , microscale chemistry , computer science , histone deacetylase , drug discovery , histone deacetylase inhibitor , throughput , chemistry , nanotechnology , combinatorial chemistry , database , histone , materials science , biochemistry , operating system , mathematics education , mathematics , wireless , gene
An integrated workflow has been established that enables the synthesis, purification, and subsequent biological testing of compound libraries on a microgram scale. This approach utilizes mass directed preparative HPLC in conjunction with charged aerosol detection (CAD) to generate solutions of investigational compounds at high purity and standardized concentrations, facilitating high fidelity biological testing. This new workflow successfully delivered libraries of histone deacetylase (HDAC) inhibitors that afforded biological data consistent with that obtained from standard scale parallel medicinal chemistry techniques. The advantages of this new approach to library synthesis include greatly reduced material requirements and amenability to high-throughput experimentation.