Literature DB >> 23226811

Simplification traps.

Heino Prinz1.   

Abstract

UNLABELLED: When experiments are analyzed with simple functions, one gets simple results. A trap springs when experiments show deviations from the expected simplicity. When kinetic experiments do not follow exponential curves, they simply are not of the first or pseudofirst order. They can and have to be calculated on the base of plausible reaction schemes. When dose-response curves are analyzed with logistic functions ("4-parameter fit") and give Hill coefficients different from one, this is an experimental result stating that more than one molecule is involved in eliciting the response. If one ignores that result, one usually finds forgiving referees, but one will loose real money when one tries to develop such an unspecific compound into a drug. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12154-011-0069-3) contains supplementary material, which is available to authorized users.

Keywords:  4PL; Dose–response curves; Logistic function; Multiexponential fits; Numerical methods; Systematic deviations

Year:  2011        PMID: 23226811      PMCID: PMC3251649          DOI: 10.1007/s12154-011-0069-3

Source DB:  PubMed          Journal:  J Chem Biol        ISSN: 1864-6158


  4 in total

1.  Quantitative high-throughput screening: a titration-based approach that efficiently identifies biological activities in large chemical libraries.

Authors:  James Inglese; Douglas S Auld; Ajit Jadhav; Ronald L Johnson; Anton Simeonov; Adam Yasgar; Wei Zheng; Christopher P Austin
Journal:  Proc Natl Acad Sci U S A       Date:  2006-07-24       Impact factor: 11.205

2.  Hill coefficients, dose-response curves and allosteric mechanisms.

Authors:  Heino Prinz
Journal:  J Chem Biol       Date:  2009-09-25

3.  Transient binding patches: a plausible concept for drug binding.

Authors:  Heino Prinz; André Schönichen
Journal:  J Chem Biol       Date:  2008-09-02

4.  Potent family-18 chitinase inhibitors: x-ray structures, affinities, and binding mechanisms.

Authors:  Supansa Pantoom; Ingrid R Vetter; Heino Prinz; Wipa Suginta
Journal:  J Biol Chem       Date:  2011-04-29       Impact factor: 5.157

  4 in total
  2 in total

1.  Post-HTS case report and structural alert: Promiscuous 4-aroyl-1,5-disubstituted-3-hydroxy-2H-pyrrol-2-one actives verified by ALARM NMR.

Authors:  Jayme L Dahlin; J Willem M Nissink; Subhashree Francis; Jessica M Strasser; Kristen John; Zhiguo Zhang; Michael A Walters
Journal:  Bioorg Med Chem Lett       Date:  2015-08-10       Impact factor: 2.823

Review 2.  The essential roles of chemistry in high-throughput screening triage.

Authors:  Jayme L Dahlin; Michael A Walters
Journal:  Future Med Chem       Date:  2014-07       Impact factor: 3.808

  2 in total

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