Beyond Thermodynamics: Drug Binding Kinetics Could Influence Epidermal Growth Factor Signaling

Mayank Goyal; Michael Rizzo; Frank Schumacher; Chung F. Wong

doi:10.1021/jm900974p

Beyond Thermodynamics: Drug Binding Kinetics Could Influence Epidermal Growth Factor Signaling

Mayank Goyal, Michael Rizzo, Frank Schumacher, Chung F. Wong

University of Missouri-St. Louis

Research output: Contribution to journal › Article › peer-review

Abstract

We modeled the kinetics of drug binding to protein kinases in the EGF signaling pathway relevant to non-small-cell lung cancer and found that binding kinetics could influence therapeutic potential, that fast binding kinetics was advantageous for most targets with a couple of exceptions, that targeting some protein kinases could enhance rather than attenuate the pathway, and that IC(50) could be sensitive to the kinetic parameters of drug binding.

Original language	American English
Journal	Journal of Medicinal Chemistry
Volume	52
DOIs	https://doi.org/10.1021/jm900974p
State	Published - Sep 24 2009

Disciplines

Biology
Biochemistry

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10.1021/jm900974pLicense: Unspecified

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title = "Beyond Thermodynamics: Drug Binding Kinetics Could Influence Epidermal Growth Factor Signaling",

abstract = " We modeled the kinetics of drug binding to protein kinases in the EGF signaling pathway relevant to non-small-cell lung cancer and found that binding kinetics could influence therapeutic potential, that fast binding kinetics was advantageous for most targets with a couple of exceptions, that targeting some protein kinases could enhance rather than attenuate the pathway, and that IC(50) could be sensitive to the kinetic parameters of drug binding. ",

author = "Mayank Goyal and Michael Rizzo and Frank Schumacher and Wong, {Chung F.}",

note = "J Med Chem. 2009 Sep 24;52(18):5582-5. doi: 10.1021/jm900974p. Research Support, Non-U.S. Gov't",

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doi = "10.1021/jm900974p",

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T1 - Beyond Thermodynamics: Drug Binding Kinetics Could Influence Epidermal Growth Factor Signaling

AU - Goyal, Mayank

AU - Rizzo, Michael

AU - Schumacher, Frank

AU - Wong, Chung F.

N1 - J Med Chem. 2009 Sep 24;52(18):5582-5. doi: 10.1021/jm900974p. Research Support, Non-U.S. Gov't

PY - 2009/9/24

Y1 - 2009/9/24

N2 - We modeled the kinetics of drug binding to protein kinases in the EGF signaling pathway relevant to non-small-cell lung cancer and found that binding kinetics could influence therapeutic potential, that fast binding kinetics was advantageous for most targets with a couple of exceptions, that targeting some protein kinases could enhance rather than attenuate the pathway, and that IC(50) could be sensitive to the kinetic parameters of drug binding.

AB - We modeled the kinetics of drug binding to protein kinases in the EGF signaling pathway relevant to non-small-cell lung cancer and found that binding kinetics could influence therapeutic potential, that fast binding kinetics was advantageous for most targets with a couple of exceptions, that targeting some protein kinases could enhance rather than attenuate the pathway, and that IC(50) could be sensitive to the kinetic parameters of drug binding.

UR - https://www.ncbi.nlm.nih.gov/pubmed/19702309

U2 - 10.1021/jm900974p

DO - 10.1021/jm900974p

M3 - Article

VL - 52

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

ER -

Beyond Thermodynamics: Drug Binding Kinetics Could Influence Epidermal Growth Factor Signaling

Abstract

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