Structure tuning of pyrazolylpyrrole derivatives as ERK inhibitors utilizing dual tools; 3D-QSAR and side-chain hopping

Mi Hyun Kim; Jae Yoon Chung; Jae Sang Ryu; Jung Mi Hah

doi:10.1016/j.bmcl.2011.06.016

Structure tuning of pyrazolylpyrrole derivatives as ERK inhibitors utilizing dual tools; 3D-QSAR and side-chain hopping

Mi Hyun Kim, Jae Yoon Chung, Jae Sang Ryu, Jung Mi Hah

Pharmaceutical Sciences

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

10 Scopus citations

Abstract

The ERK pathway is a well-known therapeutic target of cancer treatment with great advantage of selectivity between normal cells and cancer cells, and the number of direct ERK kinase inhibitors is quite limited considering large number of available ERK structure from PDB. Therefore, we tried to combine 3D-QSAR with side-chain hopping in an attempt to produce novel structures as ERK inhibitors. The predictive models with q ² value of 0.867, r ² value of 0.991 in CoMFA and q ² value of 0.628, r ² value of 0.950 in CoMSIA were used to select effective compounds from new library generated from side-chain hopping by CombiGlide.

Original language	English
Pages (from-to)	4900-4904
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	16
DOIs	https://doi.org/10.1016/j.bmcl.2011.06.016
State	Published - 15 Aug 2011

Keywords

3D-QSAR
Anticancer agent
ERK inhibitors
Pyrazolylpyrrole
Side-chain hopping

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10.1016/j.bmcl.2011.06.016

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title = "Structure tuning of pyrazolylpyrrole derivatives as ERK inhibitors utilizing dual tools; 3D-QSAR and side-chain hopping",

abstract = "The ERK pathway is a well-known therapeutic target of cancer treatment with great advantage of selectivity between normal cells and cancer cells, and the number of direct ERK kinase inhibitors is quite limited considering large number of available ERK structure from PDB. Therefore, we tried to combine 3D-QSAR with side-chain hopping in an attempt to produce novel structures as ERK inhibitors. The predictive models with q 2 value of 0.867, r 2 value of 0.991 in CoMFA and q 2 value of 0.628, r 2 value of 0.950 in CoMSIA were used to select effective compounds from new library generated from side-chain hopping by CombiGlide.",

keywords = "3D-QSAR, Anticancer agent, ERK inhibitors, Pyrazolylpyrrole, Side-chain hopping",

author = "Kim, {Mi Hyun} and Chung, {Jae Yoon} and Ryu, {Jae Sang} and Hah, {Jung Mi}",

note = "Funding Information: This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0087992; J.M.H.). ",

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doi = "10.1016/j.bmcl.2011.06.016",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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AU - Kim, Mi Hyun

AU - Chung, Jae Yoon

AU - Ryu, Jae Sang

AU - Hah, Jung Mi

N1 - Funding Information: This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0087992; J.M.H.).

PY - 2011/8/15

Y1 - 2011/8/15

N2 - The ERK pathway is a well-known therapeutic target of cancer treatment with great advantage of selectivity between normal cells and cancer cells, and the number of direct ERK kinase inhibitors is quite limited considering large number of available ERK structure from PDB. Therefore, we tried to combine 3D-QSAR with side-chain hopping in an attempt to produce novel structures as ERK inhibitors. The predictive models with q 2 value of 0.867, r 2 value of 0.991 in CoMFA and q 2 value of 0.628, r 2 value of 0.950 in CoMSIA were used to select effective compounds from new library generated from side-chain hopping by CombiGlide.

AB - The ERK pathway is a well-known therapeutic target of cancer treatment with great advantage of selectivity between normal cells and cancer cells, and the number of direct ERK kinase inhibitors is quite limited considering large number of available ERK structure from PDB. Therefore, we tried to combine 3D-QSAR with side-chain hopping in an attempt to produce novel structures as ERK inhibitors. The predictive models with q 2 value of 0.867, r 2 value of 0.991 in CoMFA and q 2 value of 0.628, r 2 value of 0.950 in CoMSIA were used to select effective compounds from new library generated from side-chain hopping by CombiGlide.

KW - 3D-QSAR

KW - Anticancer agent

KW - ERK inhibitors

KW - Pyrazolylpyrrole

KW - Side-chain hopping

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ER -

Structure tuning of pyrazolylpyrrole derivatives as ERK inhibitors utilizing dual tools; 3D-QSAR and side-chain hopping

Abstract

Keywords

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