Fragment-based lead discovery of small molecule inhibitors for the EPHA4 receptor tyrosine kinase

O.P.J. van Linden; C Farenc; W.H. Zoutman; L Hameetman; M. Wijtmans; R. Leurs; C.P. Tensen; G. Siegal; I.J.P. de Esch

doi:10.1016/j.ejmech.2011.11.020

Fragment-based lead discovery of small molecule inhibitors for the EPHA4 receptor tyrosine kinase

O.P.J. van Linden
, C Farenc
, W.H. Zoutman
, L Hameetman
, M. Wijtmans
, R. Leurs
, C.P. Tensen
, G. Siegal
, I.J.P. de Esch

AIMMS

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

The in silico identification, optimization and crystallographic characterization of a 6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-1-amine scaffold as an inhibitor for the EPHA4 receptor tyrosine kinase is described. A database containing commercially available compounds was subjected to an in silico screening procedure which was focused on finding novel, EPHA4 hinge binding fragments. This resulted in the identification of 6,7,8,9-tetrahydro-3H- pyrazolo[3,4-c]isoquinolin-1-amine derivatives as EPHA4 inhibitors. Hit exploration yielded a compound with 2 μM (IC

Original language	English
Pages (from-to)	493-500
Journal	European Journal of Medicinal Chemistry
Volume	47
DOIs	https://doi.org/10.1016/j.ejmech.2011.11.020
Publication status	Published - 2011

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being
SDG 6 Clean Water and Sanitation

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10.1016/j.ejmech.2011.11.020

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@article{cb3b882c66174544bab870f2fac7f523,

title = "Fragment-based lead discovery of small molecule inhibitors for the EPHA4 receptor tyrosine kinase",

abstract = "The in silico identification, optimization and crystallographic characterization of a 6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-1-amine scaffold as an inhibitor for the EPHA4 receptor tyrosine kinase is described. A database containing commercially available compounds was subjected to an in silico screening procedure which was focused on finding novel, EPHA4 hinge binding fragments. This resulted in the identification of 6,7,8,9-tetrahydro-3H- pyrazolo[3,4-c]isoquinolin-1-amine derivatives as EPHA4 inhibitors. Hit exploration yielded a compound with 2 μM (IC",

author = "\{van Linden\}, O.P.J. and C Farenc and W.H. Zoutman and L Hameetman and M. Wijtmans and R. Leurs and C.P. Tensen and G. Siegal and \{de Esch\}, I.J.P.",

year = "2011",

doi = "10.1016/j.ejmech.2011.11.020",

language = "English",

volume = "47",

pages = "493--500",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson s.r.l.",

}

TY - JOUR

T1 - Fragment-based lead discovery of small molecule inhibitors for the EPHA4 receptor tyrosine kinase

AU - van Linden, O.P.J.

AU - Farenc, C

AU - Zoutman, W.H.

AU - Hameetman, L

AU - Wijtmans, M.

AU - Leurs, R.

AU - Tensen, C.P.

AU - Siegal, G.

AU - de Esch, I.J.P.

PY - 2011

Y1 - 2011

N2 - The in silico identification, optimization and crystallographic characterization of a 6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-1-amine scaffold as an inhibitor for the EPHA4 receptor tyrosine kinase is described. A database containing commercially available compounds was subjected to an in silico screening procedure which was focused on finding novel, EPHA4 hinge binding fragments. This resulted in the identification of 6,7,8,9-tetrahydro-3H- pyrazolo[3,4-c]isoquinolin-1-amine derivatives as EPHA4 inhibitors. Hit exploration yielded a compound with 2 μM (IC

AB - The in silico identification, optimization and crystallographic characterization of a 6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinolin-1-amine scaffold as an inhibitor for the EPHA4 receptor tyrosine kinase is described. A database containing commercially available compounds was subjected to an in silico screening procedure which was focused on finding novel, EPHA4 hinge binding fragments. This resulted in the identification of 6,7,8,9-tetrahydro-3H- pyrazolo[3,4-c]isoquinolin-1-amine derivatives as EPHA4 inhibitors. Hit exploration yielded a compound with 2 μM (IC

U2 - 10.1016/j.ejmech.2011.11.020

DO - 10.1016/j.ejmech.2011.11.020

M3 - Article

SN - 0223-5234

VL - 47

SP - 493

EP - 500

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

Fragment-based lead discovery of small molecule inhibitors for the EPHA4 receptor tyrosine kinase

Abstract

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