9MZX

Crystal structure of human RIPK1 with Compound 1

This is a non-PDB format compatible entry.

Summary for 9MZX

• Entry DOI: 10.2210/pdb9mzx/pdb
• Descriptor: Receptor-interacting serine/threonine-protein kinase 1, 1-[(2S,5S)-2,3-dihydro-2,5-methano-1,4-benzoxazepin-4(5H)-yl]-2,2-dimethylpropan-1-one, IODIDE ION, ... (4 entities in total)
• Functional Keywords: kinase, serine/threonine-protein kinase, inhibitor, transferase, transferase-inhibitor complex, transferase/inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 67110.99

Authors

Lesburg, C.A.,Palte, R.L.,Maskos, K.,Thomsen, M.,Lammens, A. (deposition date: 2025-01-23, release date: 2025-05-28)

Primary citation

Chen, J.L.,Methot, J.L.,Mitcheltree, M.J.,Musacchio, A.,Corcoran, E.B.,Feng, G.,Lammens, A.,Maskos, K.,Palte, R.L.,Rickard, M.M.,Otte, K.M.,Mansueto, M.S.,Venkat, S.,Sondey, C.,Thomsen, M.,Lesburg, C.A.,Fradera, X.,Fell, M.J.,DiMauro, E.F.,Siliphaivanh, P.
The Discovery of Bridged Benzoazepine Amides as Selective Allosteric Modulators of RIPK1.
Acs Med.Chem.Lett., 16:811-818, 2025

PubMed Abstract: Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in necroptosis, a form of inflammatory, caspase-independent, programmed cell death. Allosteric inhibitors of RIPK1 have been shown to block necroptotic cell death and thus may offer potential therapeutic opportunities across a range of infectious, autoimmune, and neurodegenerative diseases. We report the structure-informed discovery of a novel series of bridged benzoazepine amides as part of our efforts to develop a CNS-penetrant small-molecule inhibitor of RIPK1 with a low projected oral human dose.

PubMed: 40365380
DOI: 10.1021/acsmedchemlett.5c00063

Experimental method

X-RAY DIFFRACTION (2.53 Å)