Hit-to-Lead

Hit Validation and Assessment

Kirk Hevener, Russell Pesavento, Jin Hong Ren, Hyun Lee, Kiira Ratia, Michael E. Johnson

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

High-throughput screening assays have become nearly ubiquitous in the search for small compounds or peptides that can modulate biological processes for therapeutic purposes. While many assays have become quite robust, with well-established protocols, the subsequent steps of validating the hits and choosing the best ones to take forward into leads for further chemical development are less established. In this chapter, we describe a variety of approaches, including chemical assessment, the use of various computational approaches, a variety of counter-screens, and “orthogonal” biophysical assays using nuclear magnetic resonance, surface plasmon resonance, isothermal titration calorimetry or thermal shift assays as methods for validating and assessing the quality of hits.

Original languageEnglish (US)
Title of host publicationMethods in Enzymology
EditorsCharles A. Lesburg
PublisherAcademic Press Inc.
Pages265-309
Number of pages45
ISBN (Print)9780128153833
DOIs
StatePublished - Jan 1 2018

Publication series

NameMethods in Enzymology
Volume610
ISSN (Print)0076-6879
ISSN (Electronic)1557-7988

Fingerprint

High-Throughput Screening Assays
Biological Phenomena
Calorimetry
Surface Plasmon Resonance
Assays
Magnetic Resonance Spectroscopy
Hot Temperature
Peptides
Surface plasmon resonance
Therapeutics
Titration
Screening
Throughput
Nuclear magnetic resonance
Lead

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

Hevener, K., Pesavento, R., Ren, J. H., Lee, H., Ratia, K., & Johnson, M. E. (2018). Hit-to-Lead: Hit Validation and Assessment. In C. A. Lesburg (Ed.), Methods in Enzymology (pp. 265-309). (Methods in Enzymology; Vol. 610). Academic Press Inc.. https://doi.org/10.1016/bs.mie.2018.09.022

Hit-to-Lead : Hit Validation and Assessment. / Hevener, Kirk; Pesavento, Russell; Ren, Jin Hong; Lee, Hyun; Ratia, Kiira; Johnson, Michael E.

Methods in Enzymology. ed. / Charles A. Lesburg. Academic Press Inc., 2018. p. 265-309 (Methods in Enzymology; Vol. 610).

Research output: Chapter in Book/Report/Conference proceedingChapter

Hevener, K, Pesavento, R, Ren, JH, Lee, H, Ratia, K & Johnson, ME 2018, Hit-to-Lead: Hit Validation and Assessment. in CA Lesburg (ed.), Methods in Enzymology. Methods in Enzymology, vol. 610, Academic Press Inc., pp. 265-309. https://doi.org/10.1016/bs.mie.2018.09.022
Hevener K, Pesavento R, Ren JH, Lee H, Ratia K, Johnson ME. Hit-to-Lead: Hit Validation and Assessment. In Lesburg CA, editor, Methods in Enzymology. Academic Press Inc. 2018. p. 265-309. (Methods in Enzymology). https://doi.org/10.1016/bs.mie.2018.09.022
Hevener, Kirk ; Pesavento, Russell ; Ren, Jin Hong ; Lee, Hyun ; Ratia, Kiira ; Johnson, Michael E. / Hit-to-Lead : Hit Validation and Assessment. Methods in Enzymology. editor / Charles A. Lesburg. Academic Press Inc., 2018. pp. 265-309 (Methods in Enzymology).
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