Title:
METHOD FOR DETERMINING ENDURANCE OF INTERACTION BETWEEN LIGAND AND TARGET PROTEIN IN CELL
Document Type and Number:
WIPO Patent Application WO/2017/206041
Kind Code:
A1
Abstract:
Disclosed is a method for determining the endurance of the interaction between a ligand and a target protein in a cell, comprising: (1) treating the cell with the ligand; (2) removing the ligand outside the cell; (3) collecting the cell at different time points after the ligand is removed; (4) heating the cell; (5) lysing the cell; and (6) analysing the level of soluble or insoluble target protein in a cell lysis solution as a function of time. The method can be used to determine the dissociation rate constant, residence time and dissociation half-life of the interaction between the ligand and the target protein in the cell and the time range of therapeutic duration of the ligand so as to quantitatively describe the endurance of the interaction between the ligand and the target protein in the cell and to predict the duration of pharmacological action in the cell. The method can be used to develop new drugs and discover drugs with desired binding endurance. The method can be used to design a dosage regimen, especially a time interval of drug delivery.
Inventors:
WANG SHUAI (CN)
Application Number:
PCT/CN2016/083998
Publication Date:
December 07, 2017
Filing Date:
May 31, 2016
Export Citation:
Assignee:
WANG SHUAI (CN)
International Classes:
G01N33/68
Domestic Patent References:
| WO2014093677A1 | 2014-06-19 |
Foreign References:
| CN103733067A | 2014-04-16 | |||
| CN101223447A | 2008-07-16 | |||
| CN103645324A | 2014-03-19 |
Other References:
JAFARI, R. ET AL.: "The cellular thermal shift assay for evaluating drug target interactions in cells", NATURE PROTOCOLS, vol. 9, no. 9, 7 August 2014 (2014-08-07), pages 2100 - 2122, XP055193929, Retrieved from the Internet
COPELAND, R.A. ET AL.: "Drug-target residence time and its implications for lead optimization", NATURE REVIEWS DRUG DISCOVERY, vol. 5, 1 September 2006 (2006-09-01), pages 730 - 739, XP002570141, Retrieved from the Internet
MOREAU, MORGANE J.J. ET AL.: "Quantitative determination of protein stability and ligand binding using a green fluorescent protein reporter system", MOL. BIOSYST., vol. 6, 7 May 2010 (2010-05-07), pages 1285 - 1292, XP055027468, Retrieved from the Internet
REDHEAD, M. ET AL.: "A combinatorial biophysical approach; FTSAand SPR for identifying small molecule ligands and PAINs", ANALYTICAL BIOCHEMISTRY, vol. 479, 30 March 2015 (2015-03-30), pages 63 - 73, XP029157506, Retrieved from the Internet
COPELAND, R.A. ET AL.: "Drug-target residence time and its implications for lead optimization", NATURE REVIEWS DRUG DISCOVERY, vol. 5, 1 September 2006 (2006-09-01), pages 730 - 739, XP002570141, Retrieved from the Internet
MOREAU, MORGANE J.J. ET AL.: "Quantitative determination of protein stability and ligand binding using a green fluorescent protein reporter system", MOL. BIOSYST., vol. 6, 7 May 2010 (2010-05-07), pages 1285 - 1292, XP055027468, Retrieved from the Internet
REDHEAD, M. ET AL.: "A combinatorial biophysical approach; FTSAand SPR for identifying small molecule ligands and PAINs", ANALYTICAL BIOCHEMISTRY, vol. 479, 30 March 2015 (2015-03-30), pages 63 - 73, XP029157506, Retrieved from the Internet
Attorney, Agent or Firm:
SHANGHAI GREATPOWER INTELLECTUAL PROPERTY LAW FIRM (CN)
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