6RSU

TBK1 in complex with Inhibitor compound 35

Summary for 6RSU

• Entry DOI: 10.2210/pdb6rsu/pdb
• Descriptor: Serine/threonine-protein kinase TBK1, 3,3,3-tris(fluoranyl)-1-[4-[(1~{R})-1-[2-[[(2~{S})-5-(5-propan-2-yloxypyrimidin-4-yl)-2,3-dihydro-1~{H}-benzimidazol-2-yl]amino]pyridin-4-yl]ethyl]piperazin-1-yl]propan-1-one (2 entities in total)
• Functional Keywords: kinase, innate immunity, small molecule inhibitor, immune system
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 76740.66

Authors

Panne, D.,Hillig, R.C.,Rengachari, S. (deposition date: 2019-05-22, release date: 2020-04-01, Last modification date: 2024-01-24)

Primary citation

Lefranc, J.,Schulze, V.K.,Hillig, R.C.,Briem, H.,Prinz, F.,Mengel, A.,Heinrich, T.,Balint, J.,Rengachari, S.,Irlbacher, H.,Stockigt, D.,Bomer, U.,Bader, B.,Gradl, S.N.,Nising, C.F.,von Nussbaum, F.,Mumberg, D.,Panne, D.,Wengner, A.M.
Discovery of BAY-985, a Highly Selective TBK1/IKK epsilon Inhibitor.
J.Med.Chem., 63:601-612, 2020

PubMed Abstract: The serine/threonine kinase TBK1 (TANK-binding kinase 1) and its homologue IKKε are noncanonical members of the inhibitor of the nuclear factor κB (IκB) kinase family. These kinases play important roles in multiple cellular pathways and, in particular, in inflammation. Herein, we describe our investigations on a family of benzimidazoles and the identification of the potent and highly selective TBK1/IKKε inhibitor BAY-985. BAY-985 inhibits the cellular phosphorylation of interferon regulatory factor 3 and displays antiproliferative efficacy in the melanoma cell line SK-MEL-2 but showed only weak antitumor activity in the SK-MEL-2 human melanoma xenograft model.

PubMed: 31859507
DOI: 10.1021/acs.jmedchem.9b01460

Experimental method

X-RAY DIFFRACTION (2.75 Å)