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IKK family

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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The IκB kinase (IKK)-related kinases are central to the induction of the innate type I interferon (IFN) response [8]. A set of rare autoimmune disorders known as type I interferonopathies are caused by disturbance of the homeostatic control of induction, transmission, and resolution of the type I IFN-mediated immune response [7]. Therefore, members of this signaling pathway are subject to investigation as intervention points for pharmacological inhibition [5]. Initial investigations targeted IFN-I downstream signaling, including IFN-I proteins, IFNAR and the JAK/STAT signaling pathway. For example, sifalimumab (anti-IFN-α mAb), anifrolumab (anti-IFNAR1) and the JAK inhibitors ruxolitinib and tofacitinib, can all potentially tackle the effector function of dysregulated IFN by blocking downstream IFN-I signaling, but do not contribute to reducing the production of IFN. Upstream targeting of TBK1 and/or IKKε could be effective at blocking de novo IFN-I induction by a variety of stimuli. Small molecule kinase inhibitors of TBK1/IKKε already in development for cancer may expedite investigation for inflammatory diseases also [10].

Enzymes

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IKK-alpha (component of inhibitor of nuclear factor kappa B kinase complex) Show summary » More detailed page go icon to follow link

IKK-beta (inhibitor of nuclear factor kappa B kinase subunit beta) Show summary » More detailed page go icon to follow link

IKK-epsilon (inhibitor of nuclear factor kappa B kinase subunit epsilon) Show summary » More detailed page go icon to follow link

TBK1 (TANK binding kinase 1) Show summary » More detailed page go icon to follow link

References

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How to cite this family page

Database page citation:

IKK family. Accessed on 20/04/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=578.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2019) The Concise Guide to PHARMACOLOGY 2019/20: Enzymes. Br J Pharmacol. 176 Issue S1: S297-S396.