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Time-based bioactivity analysis |
Presented By
Date
Time-Based Bioactivity Analysis
Reaxys Medicinal Chemistry
Matthew CLARK
18 May 2016
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Time-based bioactivity analysis |
R&D Solutions FOR PHARMA & LIFE SCIENCES Essential Tools and Solutions for Pharma & Life Sciences
https://www.elsevier.com/rd-solutions/pharma-and-life-sciences-solutions
Matthew Clark, Ph. D. [email protected]
https://www.elsevier.com/rd-solutions/pharma-and-life-sciences-solutionshttps://www.elsevier.com/rd-solutions/pharma-and-life-sciences-solutionshttps://www.elsevier.com/rd-solutions/pharma-and-life-sciences-solutionshttps://www.elsevier.com/rd-solutions/pharma-and-life-sciences-solutionshttps://www.elsevier.com/rd-solutions/pharma-and-life-sciences-solutionshttps://www.elsevier.com/rd-solutions/pharma-and-life-sciences-solutionshttps://www.elsevier.com/rd-solutions/pharma-and-life-sciences-solutionshttps://www.elsevier.com/rd-solutions/pharma-and-life-sciences-solutionshttps://www.elsevier.com/rd-solutions/pharma-and-life-sciences-solutionshttps://www.elsevier.com/rd-solutions/pharma-and-life-sciences-solutionshttps://www.elsevier.com/rd-solutions/pharma-and-life-sciences-solutionshttps://www.elsevier.com/rd-solutions/pharma-and-life-sciences-solutionsmailto:[email protected]
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Time-based bioactivity analysis |
Q: can you analyze activity reported for a target over time, to see the time trend of improvement?
A: Yes
Findings for PIK3 example
While the most active compound has hovered around the 1-10pM range of affinity, the scaffolds are similar
Looking over the distribution of activities reported for all PIK3-active compounds, the peak of the distribution has shifted only moderately over time.
Findings for ABL1 example
Most active compound about 10nM for some time
Number of highly active compound reports increasing over time
Trend is moving to more active compounds
Follow Up From Bioactivity Prediction Webinar Question
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Time-based bioactivity analysis |
Most Potent Compound Reported for PIK3 Target by Year
(all variants, PIK3* )
The developer of the most-binding compound over time: 2014-16 Pfizer 2011-13 GSK (GSK2126458) 2008-10 Pfizer 2000-07 Isradipine, Sandoz 1994-96 Nicarpidine, Syntex
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The scaffolds have some notable similarity over this time period
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Time-based bioactivity analysis |
The peak of reported activities has shifted only moderately
The number of compounds reported per year increased 1000 fold between 1994 and 2014
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Distribution of Activities for PIK3 Target Over Time
Graph shows the number of assay reports in each decade of activity for the given time spans That is, how the activities are distributed Note: some compounds are reported in more than one time frame.
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-log10[M] activity
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Time-based bioactivity analysis |
1994-1996 compound is from Plexxicon, most active from Princeton U., most recent from Nektar.
2000-2002 leader was Staurosporine!
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ABL1 Kinase
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Time-based bioactivity analysis |
Proportion of highly active compound reports increasing over time
Total number of compounds reported peaked in 2006-2008
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ABL1 Kinase Distribution of Activities Over Time
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Time-based bioactivity analysis |
Trend shows most active compounds have been small molecules, oligos, and most recently the cyclic peptide cyclohexylgriselimycin
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DNA Polymerase
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Time-based bioactivity analysis | 9
DNA Polymerase Distribution of Activities over Time
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Trend seems to be for fewer compounds in recent years.
