Flipped out: Structure-guided design of selective pyrazolylpyrrole ERK inhibitors

Alex M. Aronov; Christopher Baker; Guy W. Bemis; Jingrong Cao; Guanjing Chen; Pamella J. Ford; Ursula A. Germann; Jeremy Green; Michael R. Hale; Marc Jacobs; James W. Janetka; Francois Maltais; Gabriel Martinez-Botella; Mark N. Namchuk; Judy Straub; Qing Tang; Xiaoling Xie

doi:10.1021/jm061381f

Flipped out: Structure-guided design of selective pyrazolylpyrrole ERK inhibitors

Alex M. Aronov, Christopher Baker, Guy W. Bemis, Jingrong Cao, Guanjing Chen, Pamella J. Ford, Ursula A. Germann, Jeremy Green, Michael R. Hale, Marc Jacobs, James W. Janetka, Francois Maltais, Gabriel Martinez-Botella, Mark N. Namchuk, Judy Straub, Qing Tang, Xiaoling Xie

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

98 Scopus citations

Abstract

The Ras/Raf/MEK/ERK signal transduction is a key oncogenic pathway implicated in a variety of human cancers. We have identified a novel series of pyrazolylpyrroles as inhibitors of ERK. Aided by the discovery of two distinct binding modes for the pyrazolylpyrrole scaffold, structure-guided optimization culminated in the discovery of 6p, a potent and selective inhibitor of ERK.

Original language	English
Pages (from-to)	1280-1287
Number of pages	8
Journal	Journal of Medicinal Chemistry
Volume	50
Issue number	6
DOIs	https://doi.org/10.1021/jm061381f
State	Published - Mar 22 2007

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Aronov, A. M., Baker, C., Bemis, G. W., Cao, J., Chen, G., Ford, P. J., Germann, U. A., Green, J., Hale, M. R., Jacobs, M., Janetka, J. W., Maltais, F., Martinez-Botella, G., Namchuk, M. N., Straub, J., Tang, Q., & Xie, X. (2007). Flipped out: Structure-guided design of selective pyrazolylpyrrole ERK inhibitors. Journal of Medicinal Chemistry, 50(6), 1280-1287. https://doi.org/10.1021/jm061381f

Aronov, Alex M. ; Baker, Christopher ; Bemis, Guy W. ; Cao, Jingrong ; Chen, Guanjing ; Ford, Pamella J. ; Germann, Ursula A. ; Green, Jeremy ; Hale, Michael R. ; Jacobs, Marc ; Janetka, James W. ; Maltais, Francois ; Martinez-Botella, Gabriel ; Namchuk, Mark N. ; Straub, Judy ; Tang, Qing ; Xie, Xiaoling. / Flipped out : Structure-guided design of selective pyrazolylpyrrole ERK inhibitors. In: Journal of Medicinal Chemistry. 2007 ; Vol. 50, No. 6. pp. 1280-1287.

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title = "Flipped out: Structure-guided design of selective pyrazolylpyrrole ERK inhibitors",

abstract = "The Ras/Raf/MEK/ERK signal transduction is a key oncogenic pathway implicated in a variety of human cancers. We have identified a novel series of pyrazolylpyrroles as inhibitors of ERK. Aided by the discovery of two distinct binding modes for the pyrazolylpyrrole scaffold, structure-guided optimization culminated in the discovery of 6p, a potent and selective inhibitor of ERK.",

author = "Aronov, {Alex M.} and Christopher Baker and Bemis, {Guy W.} and Jingrong Cao and Guanjing Chen and Ford, {Pamella J.} and Germann, {Ursula A.} and Jeremy Green and Hale, {Michael R.} and Marc Jacobs and Janetka, {James W.} and Francois Maltais and Gabriel Martinez-Botella and Namchuk, {Mark N.} and Judy Straub and Qing Tang and Xiaoling Xie",

year = "2007",

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day = "22",

doi = "10.1021/jm061381f",

language = "English",

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Aronov, AM, Baker, C, Bemis, GW, Cao, J, Chen, G, Ford, PJ, Germann, UA, Green, J, Hale, MR, Jacobs, M, Janetka, JW, Maltais, F, Martinez-Botella, G, Namchuk, MN, Straub, J, Tang, Q & Xie, X 2007, 'Flipped out: Structure-guided design of selective pyrazolylpyrrole ERK inhibitors', Journal of Medicinal Chemistry, vol. 50, no. 6, pp. 1280-1287. https://doi.org/10.1021/jm061381f

Flipped out : Structure-guided design of selective pyrazolylpyrrole ERK inhibitors. / Aronov, Alex M.; Baker, Christopher; Bemis, Guy W.; Cao, Jingrong; Chen, Guanjing; Ford, Pamella J.; Germann, Ursula A.; Green, Jeremy; Hale, Michael R.; Jacobs, Marc; Janetka, James W.; Maltais, Francois; Martinez-Botella, Gabriel; Namchuk, Mark N.; Straub, Judy; Tang, Qing; Xie, Xiaoling.

In: Journal of Medicinal Chemistry, Vol. 50, No. 6, 22.03.2007, p. 1280-1287.

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

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T2 - Structure-guided design of selective pyrazolylpyrrole ERK inhibitors

AU - Aronov, Alex M.

AU - Baker, Christopher

AU - Bemis, Guy W.

AU - Cao, Jingrong

AU - Chen, Guanjing

AU - Ford, Pamella J.

AU - Germann, Ursula A.

AU - Green, Jeremy

AU - Hale, Michael R.

AU - Jacobs, Marc

AU - Janetka, James W.

AU - Maltais, Francois

AU - Martinez-Botella, Gabriel

AU - Namchuk, Mark N.

AU - Straub, Judy

AU - Tang, Qing

AU - Xie, Xiaoling

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AB - The Ras/Raf/MEK/ERK signal transduction is a key oncogenic pathway implicated in a variety of human cancers. We have identified a novel series of pyrazolylpyrroles as inhibitors of ERK. Aided by the discovery of two distinct binding modes for the pyrazolylpyrrole scaffold, structure-guided optimization culminated in the discovery of 6p, a potent and selective inhibitor of ERK.

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Flipped out: Structure-guided design of selective pyrazolylpyrrole ERK inhibitors

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