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@article{1373192,
author = {Řezníčková, Eva and Tenora, Lukáš and Pospíšilová, Pavlína and Galeta, Juraj and Jorda, Radek and Berka, Karel and Majer, Pavel and Potáček, Milan and Kryštof, Vladimír},
article_number = {127},
doi = {http://dx.doi.org/10.1016/j.ejmech.2017.01.018},
keywords = {Transforming growth factor beta receptor I; Protein kinase; Inhibitor; Substituted pyrrolo[1.2-b]pyrazoles},
language = {eng},
issn = {0223-5234},
journal = {European Journal of Medicinal Chemistry},
title = {ALK5 kinase inhibitory activity and synthesis of 2,3,4-substituted 5,5-dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazoles},
url = {http://dx.doi.org/10.1016/j.ejmech.2017.01.018},
volume = {2017},
year = {2017}
}
TY - JOUR
ID - 1373192
AU - Řezníčková, Eva - Tenora, Lukáš - Pospíšilová, Pavlína - Galeta, Juraj - Jorda, Radek - Berka, Karel - Majer, Pavel - Potáček, Milan - Kryštof, Vladimír
PY - 2017
TI - ALK5 kinase inhibitory activity and synthesis of 2,3,4-substituted 5,5-dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazoles
JF - European Journal of Medicinal Chemistry
VL - 2017
IS - 127
SP - 632-642
EP - 632-642
SN - 02235234
KW - Transforming growth factor beta receptor I
KW - Protein kinase
KW - Inhibitor
KW - Substituted pyrrolo[1.2-b]pyrazoles
UR - http://dx.doi.org/10.1016/j.ejmech.2017.01.018
L2 - http://dx.doi.org/10.1016/j.ejmech.2017.01.018
N2 - A series of 2,3,4-substituted 5,5-dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazoles (DPPs) was synthesized and evaluated for their ALK5 inhibition activity. The most potent compounds displayed submicromolar IC50 values for ALK5. Preliminary profiling of one of the most active compounds in a panel of 50 protein kinases revealed its selectivity for ALK5. In cells, the compounds caused dose-dependent dephosphorylation of SMAD2, a well-established substrate of ALK5. In addition, the compounds blocked translocation of SMAD2/3 to nuclei of cells stimulated with TGFb and the protein remained predominantly in cytoplasm, further confirming their molecular target. Therefore, novel DPP derivatives proved to be active as ALK5 inhibitors.
ER -
ŘEZNÍČKOVÁ, Eva, Lukáš TENORA, Pavlína POSPÍŠILOVÁ, Juraj GALETA, Radek JORDA, Karel BERKA, Pavel MAJER, Milan POTÁČEK and Vladimír KRYŠTOF. ALK5 kinase inhibitory activity and synthesis of 2,3,4-substituted 5,5-dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazoles. \textit{European Journal of Medicinal Chemistry}. 2017, vol.~2017, No~127, p.~632-642. ISSN~0223-5234. Available from: https://dx.doi.org/10.1016/j.ejmech.2017.01.018.
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