10ZJ

Structure of Cbl-B bound to compound 8

This is a non-PDB format compatible entry.

Summary for 10ZJ

• Entry DOI: 10.2210/pdb10zj/pdb
• Descriptor: E3 ubiquitin-protein ligase CBL-B, GLYCEROL, ZINC ION, ... (7 entities in total)
• Functional Keywords: ubiquitin ligase, e3, inhibitor, ligase, ligase-inhibitor complex, ligase/inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 48635.35

Authors

Murray, J.,Yu, C.,Hsu, P.L. (deposition date: 2026-02-12, release date: 2026-07-01)

Primary citation

Lambrecht, M.J.,Liang, J.,Ung, P.M.,Huestis, M.P.,Zhu, B.Y.,Barton, L.M.,Castanedo, G.M.,Zbieg, J.R.,Larouche-Gauthier, R.,Jakalian, A.,Leclerc, J.P.,Yadav, A.,Haghshenas, P.,Aubert-Nicol, S.,Ismaili, H.,Zhao, L.,Leblanc, M.,Wang, J.,Wang, S.,Wang, Q.,Garner, T.,Tan, S.,Prangley, M.,Broccatelli, F.,Pang, J.,Murray, J.,Yu, C.,Hsu, P.,Rutz, S.,Kakiuchi-Kiyota, S.,Ishizuka, I.,Leung, D.H.,Kou, P.,Bao, L.,Wang, X.
Optimization and In Vivo Characterization of a Series of Cbl‐b Inactive-State Inhibitors.
Acs Med.Chem.Lett., 17:1253-1257, 2026

PubMed Abstract: Casitas B-lineage lymphoma-b (Cbl-b), an E3 ubiquitin ligase, is a key negative regulator of immune function, and its inhibition is a promising strategy for cancer immunotherapy. Here, we show the optimization of a series of inactive-state Cbl-b inhibitors to improve their potency and pharmacokinetic properties. Through systematic modification of a benzylic amine and a linker region, compound was identified, which demonstrates a favorable balance of biochemical potency, cellular activity, and ADME properties. Despite exhibiting high IV clearance , compound achieved oral exposures sufficient to demonstrate significant tumor growth inhibition in a murine CT26 colon-cancer model.

PubMed: 42305211
DOI: 10.1021/acsmedchemlett.6c00103

Experimental method

X-RAY DIFFRACTION (1.77 Å)