M. Protopopov, V. Vdovin, S. S. Lukashov, O. V. Ostrynska, I. Borysenko, O. Borovykov, S. Starosyla, Y. Bilokin, O. P. Kukharenko, V. Bdzhola, S. Yarmoluk
{"title":"新型异芳基氨基-3-芳基-1H-吲唑类蛋白激酶CK2抑制剂的体外活性评价及SAR研究","authors":"M. Protopopov, V. Vdovin, S. S. Lukashov, O. V. Ostrynska, I. Borysenko, O. Borovykov, S. Starosyla, Y. Bilokin, O. P. Kukharenko, V. Bdzhola, S. Yarmoluk","doi":"10.7124/BC.000A4C","DOIUrl":null,"url":null,"abstract":"Aim. To identify novel protein kinase CK2 inhibitors among the 5-hetarylamino-1H-indazoles. Methods. Biochemical testing was carried out with the aid of γ- 32 P ATP in vitro kinase assay. Molecular docking via the Autodock 4.2.6 program package was executed, rescoring of docking results was performed using DrugScore scoring function. Results. Among the 17 studied 5-amino-3-arylindazole derivatives 11 inhibitors of protein kinase CK2 with IC 50 in nanomolar range were identified. The most active compound has IC 50 = 2 nM. SAR study and addi-tional molecular modeling of these compounds allowed us to select prospective substituents for construction of novel compounds with improved activity and physicochemical properties. Conclusions. As a result of this work 11 nanomolar protein kinase CK2 inhibitors were de-veloped and the binding modes of these compounds with the ATP-acceptor site were proposed using molecular docking methods. The physicochemical properties and SAR of substituents of studied compounds were analyzed and 6 novel compounds were designed for further development as protein kinase CK2 inhibitors. Summarizing, 5-heterylamino-1H-indazoles are a good basis for further CK2 inhibitors development.","PeriodicalId":39444,"journal":{"name":"Biopolymers and Cell","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2021-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Evaluation of in vitro activity and SAR study of the novel hetarylamino-3-aryl-1H-indazole derivatives as inhibitors of protein kinase CK2\",\"authors\":\"M. Protopopov, V. Vdovin, S. S. Lukashov, O. V. Ostrynska, I. Borysenko, O. Borovykov, S. Starosyla, Y. Bilokin, O. P. Kukharenko, V. Bdzhola, S. Yarmoluk\",\"doi\":\"10.7124/BC.000A4C\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Aim. To identify novel protein kinase CK2 inhibitors among the 5-hetarylamino-1H-indazoles. Methods. Biochemical testing was carried out with the aid of γ- 32 P ATP in vitro kinase assay. Molecular docking via the Autodock 4.2.6 program package was executed, rescoring of docking results was performed using DrugScore scoring function. Results. Among the 17 studied 5-amino-3-arylindazole derivatives 11 inhibitors of protein kinase CK2 with IC 50 in nanomolar range were identified. The most active compound has IC 50 = 2 nM. SAR study and addi-tional molecular modeling of these compounds allowed us to select prospective substituents for construction of novel compounds with improved activity and physicochemical properties. Conclusions. As a result of this work 11 nanomolar protein kinase CK2 inhibitors were de-veloped and the binding modes of these compounds with the ATP-acceptor site were proposed using molecular docking methods. The physicochemical properties and SAR of substituents of studied compounds were analyzed and 6 novel compounds were designed for further development as protein kinase CK2 inhibitors. Summarizing, 5-heterylamino-1H-indazoles are a good basis for further CK2 inhibitors development.\",\"PeriodicalId\":39444,\"journal\":{\"name\":\"Biopolymers and Cell\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2021-02-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biopolymers and Cell\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.7124/BC.000A4C\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biopolymers and Cell","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.7124/BC.000A4C","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
Evaluation of in vitro activity and SAR study of the novel hetarylamino-3-aryl-1H-indazole derivatives as inhibitors of protein kinase CK2
Aim. To identify novel protein kinase CK2 inhibitors among the 5-hetarylamino-1H-indazoles. Methods. Biochemical testing was carried out with the aid of γ- 32 P ATP in vitro kinase assay. Molecular docking via the Autodock 4.2.6 program package was executed, rescoring of docking results was performed using DrugScore scoring function. Results. Among the 17 studied 5-amino-3-arylindazole derivatives 11 inhibitors of protein kinase CK2 with IC 50 in nanomolar range were identified. The most active compound has IC 50 = 2 nM. SAR study and addi-tional molecular modeling of these compounds allowed us to select prospective substituents for construction of novel compounds with improved activity and physicochemical properties. Conclusions. As a result of this work 11 nanomolar protein kinase CK2 inhibitors were de-veloped and the binding modes of these compounds with the ATP-acceptor site were proposed using molecular docking methods. The physicochemical properties and SAR of substituents of studied compounds were analyzed and 6 novel compounds were designed for further development as protein kinase CK2 inhibitors. Summarizing, 5-heterylamino-1H-indazoles are a good basis for further CK2 inhibitors development.
Biopolymers and CellBiochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
1.10
自引率
0.00%
发文量
9
期刊介绍:
“Biopolymer and cell” is published since 1985 at the Institute of Molecular Biology and Genetics NAS of Ukraine under the supervision of the National Academy of Sciences of Ukraine. Our journal covers a wide scope of problems related to molecular biology and genetics including structural and functional genomics, transcriptomics, proteomics, bioinformatics, biomedicine, molecular enzymology, molecular virology and immunology, theoretical bases of biotechnology, physics and physical chemistry of proteins and nucleic acids and bioorganic chemistry.