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. 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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Basic information
Original name ALK5 kinase inhibitory activity and synthesis of 2,3,4-substituted 5,5-dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazoles
Authors ŘEZNÍČKOVÁ, Eva (203 Czech Republic), Lukáš TENORA (203 Czech Republic, belonging to the institution), Pavlína POSPÍŠILOVÁ (203 Czech Republic), Juraj GALETA (703 Slovakia, belonging to the institution), Radek JORDA (203 Czech Republic), Karel BERKA (203 Czech Republic), Pavel MAJER (203 Czech Republic), Milan POTÁČEK (203 Czech Republic, belonging to the institution) and Vladimír KRYŠTOF (203 Czech Republic).
Edition European Journal of Medicinal Chemistry, 2017, 0223-5234.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10401 Organic chemistry
Country of publisher France
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 4.816
RIV identification code RIV/00216224:14310/17:00096184
Organization unit Faculty of Science
Doi http://dx.doi.org/10.1016/j.ejmech.2017.01.018
UT WoS 000397172800051
Keywords in English Transforming growth factor beta receptor I; Protein kinase; Inhibitor; Substituted pyrrolo[1.2-b]pyrazoles
Tags NZ, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Marie Šípková, DiS., učo 437722. Changed: 23/4/2020 15:36.
Abstract
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.
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LM2015047, research and development projectName: Česká národní infrastruktura pro biologická data (Acronym: ELIXIR-CZ)
Investor: Ministry of Education, Youth and Sports of the CR, Czech National Infrastructure for Biological Data
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