Virtual high-throughput screens identifying hPK-M2 inhibitors: Exploration of model extrapolation. (February 2019)
- Record Type:
- Journal Article
- Title:
- Virtual high-throughput screens identifying hPK-M2 inhibitors: Exploration of model extrapolation. (February 2019)
- Main Title:
- Virtual high-throughput screens identifying hPK-M2 inhibitors: Exploration of model extrapolation
- Authors:
- Chen, Jonathan J.
Schmucker, Lyndsey N.
Visco, Donald P. - Abstract:
- Graphical abstract: Highlights: Trained predictive SVM classification/regression models with available hPK-M2 data. Screened PubChem Compound Database, ∼72 million compounds, for lead candidates. Select candidates identified and purchased for activity validation experiments. Candidate screening hit-rate: 1st round – 1/12 (8.13%), 2nd round – 6/11 (54.5%). 2nd round result analysis for extrapolation effects: stepwise extrapolation advised. Abstract: Glycolysis with PK-M2 occurs typically in anaerobic conditions and atypically in aerobic conditions, which is known as the Warburg effect. The Warburg effect is found in many oncogenic situations and is believed to provide energy and biomass for oncogenesis to persist. The work presented targets human PK-M2 (hPK-M2) in a virtual high-throughput screen to identify new inhibitors and leads for further study. In the initial screen, one of the 12 candidates selected for experimental validation showed biological activity (hit-rate = 8.13%). In the second screen with retrained models, six of 11 candidates selected for experimental validation showed biological activity (hit-rate: 54.5%). Additionally, four different scaffolds were identified for further analysis when examining the tested candidates and compounds in the training data. Finally, extrapolation was necessary to identify a sufficient number of candidates to test in the second screen. Examination of the results suggested stepwise extrapolation to maximize efficiency.
- Is Part Of:
- Computational biology and chemistry. Volume 78(2019)
- Journal:
- Computational biology and chemistry
- Issue:
- Volume 78(2019)
- Issue Display:
- Volume 78, Issue 2019 (2019)
- Year:
- 2019
- Volume:
- 78
- Issue:
- 2019
- Issue Sort Value:
- 2019-0078-2019-0000
- Page Start:
- 317
- Page End:
- 329
- Publication Date:
- 2019-02
- Subjects:
- Human PK-M2 -- Virtual high-throughput screening -- Data mining -- QSAR -- Drug discovery -- Signature
Chemistry -- Data processing -- Periodicals
Biology -- Data processing -- Periodicals
Biochemistry -- Data processing
Biology -- Data processing
Molecular biology -- Data processing
Periodicals
Electronic journals
542.85 - Journal URLs:
- http://www.sciencedirect.com/science/journal/14769271 ↗
http://www.elsevier.com/journals ↗ - DOI:
- 10.1016/j.compbiolchem.2018.12.006 ↗
- Languages:
- English
- ISSNs:
- 1476-9271
- Deposit Type:
- Legaldeposit
- View Content:
- Available online (eLD content is only available in our Reading Rooms) ↗
- Physical Locations:
- British Library DSC - 3390.576700
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British Library STI - ELD Digital store - Ingest File:
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