Recent progress in small molecule TBK1 inhibitors: a patent review (2015– 2020)

References

• Yin M, Wang X, Lu J. Advances in IKBKE as a potential target for cancer therapy. Can Med.. 2020;9(1):247–258.
   Google Scholar
• Verhelst K, Verstrepen L, Carpentier I, et al. IkB kinase ε (IKK): a therapeutic target in inflammation and cancer. Biocem Pharmacol.. 2013;85(7):873–880.
   PubMed Web of Science ®Google Scholar
• Ramadass V, Vaiyapuri T, Tergaonkar V. Small molecule NF-κB pathway inhibitors in clinic. Int J Mol Sci. 2020;21(14):5164.
   Web of Science ®Google Scholar
• Thomson DW, Poeckel D, Zinn N, et al. Discovery of GSK8612, a highly selective and potent TBK1 inhibitor. ACS Med Chem Lett. 2019;10(5):780–785.
   PubMed Web of Science ®Google Scholar
• Hasan M, Yan N. Therapeutic potential of targeting TBK1 in autoimmune diseases and interferonopathies. Pharmacol Res. 2016;111:336–342. .
   PubMed Web of Science ®Google Scholar
• Zhao C, Zhao W. TANK-binding kinase 1 as a novel therapeutic target for viral diseases. Expert Opin Ther Targets. 2019;23(5):437–446. .
   PubMed Web of Science ®Google Scholar
• Tanaka Y, Chen ZJ. STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway. 2012;214:ra20. Sci. Signaling.
   Google Scholar
• Louis C, Burns C, Wicks I. TANK-binding kinase 1- dependent responses in health and autoimmunity. Front Immunol. 2018;9:434.
   PubMed Web of Science ®Google Scholar
• Ullah MO, Sweet MJ, Mansell A, et al. TRIF Dependent TLR signaling, Its functions in host defense and inflammation, and its potential as a therapeutic target. J. Leukocyte Biol.. 2016;100(1):27–45.
   PubMed Web of Science ®Google Scholar
• Longhi MP, Trumpfheller C, Idoyaga J, et al. Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with Poly IC as Adjuvant. J Exp Med. 2009;206(7):1589–1602.
   PubMed Web of Science ®Google Scholar
• Muskardin TLW, Niewold TB. Type I interferon in rheumatic diseases. Nat Rev Rheumatol. 2018;14(4):214–228.
   PubMed Web of Science ®Google Scholar
• Jin J, Xiao Y, Chang J-H, et al. The kinase TBK1 controls IgA class switching by negatively regulating noncanonical NF-ΚB signaling. Nat Immunol. 2012;13(11):1101–1109.
   PubMed Web of Science ®Google Scholar
• Marchlik E, Thakker P, Carlson T, et al. Tbk1 activity exhibit immune cell infiltrates in multiple tissues and increased susceptibility to LPS-induced lethality. J. Leukocyte Biol.. 2010;88(6):1171–1180.
   PubMed Web of Science ®Google Scholar
• Cruz VH, Brekken RA. Assessment of TANK-binding kinase 1 as a therapeutic target in cancer. J. Cell Commum. Signal. 2018;12(1): 83–90. .
   PubMed Web of Science ®Google Scholar
• Ramanjulu JM, Pesiridis GS, Yang J, et al. Design of amidobenzimidazole STING receptor agonists with systemic activity. Nature 2018;564(7736):439–443.
   PubMed Web of Science ®Google Scholar
• Chiang S-H, Bazuine M, Lumeng CN, et al. The protein kinase ikkepsilon regulates energy balance in obese mice. Cell 2009;138(5):961–975.
   PubMed Web of Science ®Google Scholar
• Zhao P, Wong KI, Sun X, et al. TBK1 at the crossroads of inflammation and energy homeostasis in adipose tissue. Cell. 2018;172(4):731–743.
   PubMed Web of Science ®Google Scholar
• Reilly SM, Chiang S-H, Decker SJ, et al. An inhibitor of the protein kinases TBK1 and IKK-ε improves obesity-related metabolic dysfunctions in mice. Nat Med. 2013;19(3):313–321.
   PubMed Web of Science ®Google Scholar
• Makino H, Saijo T, Ashida Y, et al. Mechanism of action of an antiallergic agent, amlexanox (AA-673), in inhibiting histamine release from mast cells. Acceleration of cAMP generation and inhibition of phosphodiesterase. International Archives of Allergy and Applied Immunology. 1987;82(1):66–71.
   PubMedGoogle Scholar
• Bell J. Amlexanox for the treatment of recurrent aphthous ulcers. Clinical drug investigation.. 2005;25(9):555–566.
   PubMed Web of Science ®Google Scholar
• Cirulli ET, Lasseigne BN, Petrovski S, et al.,, . Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science. 2015;347(6229):1436–1441.
   PubMed Web of Science ®Google Scholar
• Freischmidt A, Wieland T, Richter B, et al. Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia. Nat Neurosci. 2015;18(5):631–636.
   PubMed Web of Science ®Google Scholar
• Majo M, Topp SD, Smith BN, et al. ALS-associated missense and nonsense TBK1 mutations can both cause loss of kinase function. Neurobiol Aging. 2018;71:266.e1-266.e10.
   PubMed Web of Science ®Google Scholar
• Gerbino V, Kaunga E, Ye J, et al. The loss of TBK1 kinase activity in motor neurons or in all cell types differentially impacts ALS disease progression in SOD1 mice. Neuron 2020;106(5):789–805.
   PubMed Web of Science ®Google Scholar
• Oakes JA, Davies MC, Collins MO. TBK1: a new player in ALS linking autophagy and neuroinflammation. Mol Brain. 2017;10(1):5. .
   PubMed Web of Science ®Google Scholar
• Pilli M, Arko-Mensah J, Ponpuak M, et al. TBK-1 promotes autophagy-mediated antimicrobial defense by controlling autophagosome maturation. Immunity 2010;37(2):223–234.
   Web of Science ®Google Scholar
• Clark K, Plater L, Peggie M, et al. Use of pharmacological inhibitor BX795 to study the regulation and physiological roles of TBK1 and IκB Kinase ε: a distinct upstream kinase mediates Ser-172 phosphorylation and activation. J Biol Chem. 2009;284(21):14136–14146.
   PubMed Web of Science ®Google Scholar
• Bain J, Plater L, Elliott M, et al. The selectivity of protein kinases inhibitors: a further update. Biochem J. 2007;408(3):297–315.
   PubMed Web of Science ®Google Scholar
• Clark K, Peggie M, Plater L, et al. Novel cross-talk within the IKK family controls innate immunity. Biochem J. 2011;434(1):93–104.
   PubMed Web of Science ®Google Scholar
• Clark K, Takeuchi O, Akira S, et al. The TRAF-associated protein TANK facilitates cross-talk within IkappaB kinase family during toll-like receptor signaling. Proc Natl Acad Sci USA. 2011;108(41):17093–17098.
   PubMed Web of Science ®Google Scholar
• Yu T, Yang Y, Yin DQ, et al. TBK1 Inhibitors: a review of patent literature (2011– 2014). Expert Opin Ther Pat. 2015;25(12):1385–1396.
   PubMed Web of Science ®Google Scholar
• The General Hospital Corporation. Methods relating to DNA-sensing pathway related conditions. US20150202223 (2015).
   Google Scholar
• The General Hospital Corporation. Targeting innate immune signaling in neuroinflammation and neurodegeneration. WO2017173451 (2017).
   Google Scholar
• The Regents of the University of Michigan. Combinations of IKKe/TBK1 Inhibitors with beta adrenergic agonists or sympathetic nervous system activators. WO2015119624 (2015).
   Google Scholar
• The Regents of the University of California. Compositions and methods for treating cancer and diseases and conditions responsive to cell growth inhibition. US20160015709 (2016).
   Google Scholar
• Dana-Farber Cancer Institute Inc. Modulating biomarkers to increase tumor immunity and improve the efficacy of cancer immunotherapy. WO2019014663 (2019).
   Google Scholar
• Dana-Farber Cancer Institute Inc. Methods for sensitizing cancer cells to T cell-mediated killing by modulating molecular pathways. WO2018226685 (2018).
   Google Scholar
• CAMP4 Therapeutics Corporation. Methods and compositions for treating urea cycle disorders, in particular OTC deficiency. WO2019071276 (2019).
   Google Scholar
• Rosa Karl. Transfection method comprising nonviral gene delivery systems. US20190264228 (2019).
   Google Scholar
• Rosa Karl. Transfection method comprising nonviral gene delivery systems. WO2018019341 (2018).
   Google Scholar
• Precision Biosciences Inc. Methods for reducing DNA-induced cytotoxicity and enhancing gene editing in primary cells. WO2018201144 (2018).
   Google Scholar
• Domainex. Pyrimidine compounds as inhibitors of protein kinases IKK epsilon and/or TBK1, Processes for their Preparation, and pharmaceutical compositions containing them. WO010826; (2012).
   Google Scholar
• Domainex Limited. 5-(Pyrimidin-4-yl)-2-(pyrrolidin-1-yl)nicotinonitrile Compounds as IKKE, TBK1 and/or SIK2 Kinases inhibitors. WO2018154315 (2018).
   Google Scholar
• Merck Patent GmbH. Thiazole derivatives. US9249114 (2016).
   Google Scholar
• Merck Patent GmbH. Pyrimidine TBK/IKKε Inhibitor compounds and uses thereof. WO2019079375 (2019).
   Google Scholar
• Merck Patent GmbH. Pyrimidine TBK/IKKε inhibitor compounds and uses thereof. WO2019079373 (2019).
   Google Scholar
• Merck Patent GmbH. TBK/IKK inhibitor compounds and uses thereof. US20160376283 (2016).
   Google Scholar
• Gilead Sciences. Tank-binding kinase inhibitor compounds. US2015344473 (2015).
   Google Scholar
• Gilead Sciences. Aminotriazine derivatives useful as TANK-binding kinase inhibitor compounds. WO2016049211 (2016).
   Google Scholar
• Gilead Sciences. Tank-binding kinase inhibitor compounds. WO2017106556 (2017).
   Google Scholar
• Takeda Pharmaceutical Company. Heteroarylamide Inhibitors of TBK1. WO2015134171 (2015).
   Google Scholar
• Takeda Pharmaceutical Company. Heteroarylamide Inhibitors of TBK1. WO2016057338 (2016).
   Google Scholar
• Heymann F, Hamesch K, Weiskirchen R, et al. The concanavalin a model of acute hepatitis in mice. Lab Anim-UK.. 2015;49(1_suppl):12–20.
   PubMedGoogle Scholar
• Green Cross Corporation. Pyrazole derivatives as TNIK, IKKe and TBK1 inhibitors and pharmaceutical composition comprising same. US20160289196 (2016).
   Google Scholar
• Green Cross Corporation. 7-Azaindole or 4,7-diazaindole derivatives as IKK epsilon and TBK1 inhibitor and pharmaceutical composition comprising same. US20160297815 (2016).
   Google Scholar
• Green Cross Corporation. Compounds as TNIK, IKK epsilon and TBK1 inhibitors and pharmaceutical composition comprising same. US20160311772 (2016).
   Google Scholar
• Yamada T, Masuda M. Emergence of TNIK inhibitors in cancer therapeutics. Cancer Sci. 2017;108(5):818–823.
   PubMed Web of Science ®Google Scholar
• Bayer Pharma. Substituted heteroarylbenzimidazole compounds. WO2017207534 (2017).
   Google Scholar
• Bayer Pharma. Substituted heteroarylbenzimidazole compounds. WO2017102091 (2017).
   Google Scholar
• Lefranc J, Schulze VK, Hillig RC, et al. Discovery of BAY-985, a highly selective TBK1/IKKε inhibitor. J Med Chem. 2020;63(2):601–612. .
   PubMed Web of Science ®Google Scholar
• GlaxoSmithKline. TBK1 inhibitor compounds. WO2019233891 (2019).
   Google Scholar
• Toure M, Crews CM. Small molecule PROTACs: new approaches to protein degradation. Angew Chem Int Ed. 2016;55(6):1966–1973.
   PubMed Web of Science ®Google Scholar
• Arvinas Inc. Tank-binding Kinase-1 protacs and associated methods of use. WO2016197114 (2016).
   Google Scholar
• Arvinas Inc. Cereblon Ligands and Bifunctional Compounds Comprising the Same. US20180215731 (2018).
   Google Scholar
• Arvinas Inc. Imide-based modulators of proteolysis and associated methods of use. US20160058872 (2016).
   Google Scholar
• Arvinas Inc. Imide-based modulators of proteolysis and associated methods of use. US20150291562 (2016).
   Google Scholar
• Crew AP, Raina K, Dong H, et al. Identification and characterization of von Hippel-Lindau-recruiting proteolysis targeting chimeras (PROTACs) of TANK-binding kinase 1. J Med Chem. 2018;61(2):583–598. .
   PubMed Web of Science ®Google Scholar