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Journal of Enzyme Inhibition and Medicinal Chemistry Volume 37, 2022 - Issue 1
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Research Papers

Identification of 1H-pyrazolo[3,4-b]pyridine derivatives as novel and potent TBK1 inhibitors: design, synthesis, biological evaluation, and molecular docking study

Yin Suna Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, P. R. China;b Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. ChinaView further author information
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Haotian Tangb Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. China;c University of Chinese Academy of Sciences, Beijing, P. R. ChinaView further author information
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Xiaoyan Wanga Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, P. R. China;b Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. ChinaView further author information
,
Fang Fengb Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. ChinaView further author information
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Tiantian Fanb Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. China;c University of Chinese Academy of Sciences, Beijing, P. R. ChinaView further author information
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Dongmei Zhaoa Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, P. R. ChinaCorrespondence[email protected]
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Bing Xiongb Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. China;c University of Chinese Academy of Sciences, Beijing, P. R. ChinaCorrespondence[email protected]
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Hua Xieb Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. China;c University of Chinese Academy of Sciences, Beijing, P. R. China;d Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. ChinaCorrespondence[email protected]
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&
Tongchao Liub Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. ChinaCorrespondence[email protected]
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Pages 1411-1425 | Received 01 Mar 2022, Accepted 21 Apr 2022, Published online: 19 May 2022

References

  • Revach OY, Liu S, Jenkins RW. Targeting tank-binding kinase 1 (tbk1) in cancer. Expert Opin Ther Targets 2020;24:1411–78.
  • Zhou R, Zhang Q, Xu P. Tbk1, a central kinase in innate immune sensing of nucleic acids and beyond. Acta Biochim Biophys Sin 2020;52:757–67.
  • Xiang S, Song S, Tang H, et al. Tank-binding kinase 1 (TBK1): an emerging therapeutic target for drug discovery. Drug Discov Today 2021;26:2445–55.
  • Lee DF, Hung MC. Advances in targeting IKK and IKK-related kinases for cancer therapy. Clin Cancer Res 2008;14:5656–62.
  • Larabi A, Devos JM, Ng SL, et al. Crystal structure and mechanism of activation of tank-binding kinase 1. Cell Rep 2013;3:734–46.
  • Muvaffak A, Pan Q, Yan H, et al. Evaluating TBK1 as a therapeutic target in cancers with activated IRF3. Mol Cancer Res 2014;12:1055–66.
  • Louis C, Burns C, Wicks I. Tank-binding kinase 1-dependent responses in health and autoimmunity. Front Immunol 2018;9:434.
  • Marion JD, Roberts CF, Call RJ, et al. Mechanism of endogenous regulation of the type I interferon response by suppressor of IκB kinase epsilon (SIKE), a novel substrate of TANK-binding kinase 1 (TBK1). J Biol Chem 2013;288:18612–23.
  • Yu T, Yang Y, Yin DQ, et al. TBK1 inhibitors: a review of patent literature (2011–2014). Expert Opin Ther Pat 2015;25:1385–96.
  • Chen Q, Sun L, Chen ZJ. Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing. Nat Immunol 2016;17:1142–9.
  • Wang X, Teng F, Lu J, et al. Expression and prognostic role of IKBKE and TBK1 in stage I non-small cell lung cancer. Cancer Manag Res 2019;11:6593–602.
  • Wei C, Cao Y, Yang X, et al. Elevated expression of tank-binding kinase 1 enhances tamoxifen resistance in breast cancer. Proc Natl Acad Sci USA 2014;111:E601–610.
  • Shen RR, Hahn WC. Emerging roles for the non-canonical IKKs in cancer. Oncogene 2011;30:631–41.
  • Chen W, Luo K, Ke Z, et al. TBK1 promote bladder cancer cell proliferation and migration via Akt signaling. J Cancer 2017;8:1892–9.
  • Scuderi SA, Lanza M, Casili G, et al. TBK1 inhibitor exerts antiproliferative effect on glioblastoma multiforme cells. Oncol Res 2021;28:779–90.
  • Eskiocak B, McMillan EA, Mendiratta S, et al. Biomarker accessible and chemically addressable mechanistic subtypes of BRAF melanoma. Cancer Discov 2017;7:832–51.
  • Yasui L, Baker N, Savage H, Der C. Ultrastructure of human pancreatic cancer cells treated with a TBK1 inhibitor. Microsc Microanal 2019;25:1284–5.
  • Yang S, Imamura Y, Jenkins RW, et al. Autophagy inhibition dysregulates TBK1 signaling and promotes pancreatic inflammation. Cancer Immunol Res 2016;4:520–30.
  • Barbie DA, Tamayo P, Boehm JS, et al. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature 2009;462:108–12.
  • Clark K, Plater L, Peggie M, Cohen P. Use of the pharmacological inhibitor BX795 to study the regulation and physiological roles of TBK1 and IkappaB kinase epsilon: a distinct upstream kinase mediates ser-172 phosphorylation and activation. J Biol Chem 2009;284:14136–46.
  • Yu T, Wang Z, Jie W, et al. The kinase inhibitor bx795 suppresses the inflammatory response via multiple kinases. Biochem Pharmacol 2020;174:113797.
  • Tu D, Zhu Z, Zhou AY, et al. Structure and ubiquitination-dependent activation of tank-binding kinase 1. Cell Rep 2013;3:747–58.
  • Clark K, Peggie M, Plater L, et al. Novel cross-talk within the IKK family controls innate immunity. Biochem J 2011;434:93–104.
  • Petherick KJ, Conway OJ, Mpamhanga C, et al. Pharmacological inhibition of ULK1 kinase blocks mammalian target of rapamycin (mTOR)-dependent autophagy. J Biol Chem 2015;290:11376–83.
  • Jenkins RW, Aref AR, Lizotte PH, et al. Ex vivo profiling of PD-1 blockade using organotypic tumor spheroids. Cancer Discov 2018;8:196–215.
  • Thomson DW, Poeckel D, Zinn N, et al. Discovery of GSK8612, a highly selective and potent TBK1 inhibitor. ACS Med Chem Lett 2019;10:780–5.
  • Lefranc J, Schulze VK, Hillig RC, et al. Discovery of BAY-985, a highly selective TBK1/IKKε inhibitor. J Med Chem 2020;63:601–12.
  • Nam Y, Hwang D, Kim N, et al. Identification of 1H-pyrazolo[3,4-b]pyridine derivatives as potent ALK-L1196M inhibitors. J Enzyme Inhib Med Chem 2019;34:1426–38.
  • Pfaffenrot B, Klovekorn P, Juchum M, et al. Design and synthesis of 1H-pyrazolo[3,4-b]pyridines targeting mitogen-activated protein kinase 4 (MKK4) - a promising target for liver regeneration. Eur J Med Chem 2021;218:113371.

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