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CCLab--a multi-objective genetic algorithm based combinatorial library design software and an application for histone deacetylase inhibitor design
- Source :
- Bioorganicmedicinal chemistry letters. 22(14)
- Publication Year :
- 2012
-
Abstract
- The introduction of the multi-objective optimization has dramatically changed the virtual combinatorial library design, which can consider many objectives simultaneously, such as synthesis cost and drug-likeness, thus may increase positive rates of biological active compounds. Here we described a software called CCLab (Combinatorial Chemistry Laboratory) for combinatorial library design based on the multi-objective genetic algorithm. Tests of the convergence ability and the ratio to re-take the building blocks in the reference library were conducted to assess the software in silico, and then it was applied to a real case of designing a 5 × 6 HDAC inhibitor library. Sixteen compounds in the resulted library were synthesized, and the histone deactetylase (HDAC) enzymatic assays proved that 14 compounds showed inhibitory ratios more than 50% against tested 3 HDAC enzymes at concentration of 20 μg/mL, with IC50 values of 3 compounds comparable to SAHA. These results demonstrated that the CCLab software could enhance the hit rates of the designed library and would be beneficial for medicinal chemists to design focused library in drug development (the software can be downloaded at: http://202.127.30.184:8080/drugdesign.html ).
- Subjects :
- Library design
medicine.drug_class
In silico
Clinical Biochemistry
Pharmaceutical Science
Computational biology
Biochemistry
Multi-objective optimization
Histone Deacetylases
Structure-Activity Relationship
Software
Software Design
Drug Discovery
Genetic algorithm
HDAC inhibitor
medicine
Combinatorial Chemistry Techniques
Molecular Biology
Molecular Structure
business.industry
Chemistry
Organic Chemistry
Histone deacetylase inhibitor
Combinatorial chemistry
Histone Deacetylase Inhibitors
Drug development
Molecular Medicine
business
Algorithms
Subjects
Details
- ISSN :
- 14643405
- Volume :
- 22
- Issue :
- 14
- Database :
- OpenAIRE
- Journal :
- Bioorganicmedicinal chemistry letters
- Accession number :
- edsair.doi.dedup.....c46e6c2071ac5554bac5a0abd73fc4f1