9Y7D

Cereblon with Golcadomide and Ikaros ZF1-2-3

This is a non-PDB format compatible entry.

Summary for 9Y7D

• Entry DOI: 10.2210/pdb9y7d/pdb
• EMDB information: 43788 72653
• Descriptor: Protein cereblon, DNA-binding protein Ikaros, ZINC ION, ... (4 entities in total)
• Functional Keywords: liganded cereblon ligase substrate, ligase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 59868.58

Authors

Watson, E.R.,Lander, G.C. (deposition date: 2025-09-09, release date: 2025-10-15, Last modification date: 2026-04-29)

Primary citation

Mo, Z.,Groocock, L.,Wood, S.,Jankeel, D.,Mendy, D.,Watson, E.R.,Kai, Y.,Deb, G.,Cote, M.,Janardhanan, P.,Fernandez-Deudero, A.,Barnes, L.,Peng, S.,Groza, M.,Kalashnikova, E.,Angelo, M.,Zhu, J.,Galasso, R.,Jang, I.S.,Castillo, M.S.,Fontanillo, C.,Polido, G.,Christoforou, A.,Kercher, T.,Lander, G.C.,Wang, K.,Narla, R.K.,Carrancio, S.,Pierce, D.W.,Rolfe, M.,Bence, N.,Lopez-Girona, A.
Golcadomide: An Oral CELMoD Agent Targeting IKZF1/3 for Diffuse Large B-cell Lymphoma.
Blood Cancer Discov, 7:104-128, 2026

PubMed Abstract: Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous disease with limited treatment options and a poor prognosis, especially for patients refractory to standard therapies. We report the discovery of golcadomide (CC-99282), an oral cereblon-modulating CELMoD agent designed using target-specific knowledge and optimized pharmacologic properties for the treatment of DLBCL. Golcadomide exhibited rapid, deep, and sustained degradation of transcription factors IKZF1 and IKZF3, surpassing the antitumor activity of the IMiD agent lenalidomide in preclinical models. In human lymphoma cell lines, golcadomide downregulated MYC, activated IFN-stimulated genes, and promoted antiproliferation, apoptosis, and immunogenic cell death. In mouse xenografts, golcadomide preferentially distributed to tissues known to be affected by lymphoma, resulting in enhanced tumor regression and tumor-free outcomes. Pharmacologic and CRISPR screening further revealed genes and pathways underlying golcadomide's antitumor efficacy. These findings supported golcadomide as a promising drug candidate for DLBCL, providing a strong rationale for future golcadomide-based regimens.

PubMed: 41182271
DOI: 10.1158/2643-3230.BCD-25-0059

Experimental method

ELECTRON MICROSCOPY (3.26 Å)