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- EMDB-72652: Cereblon-DDB1 with Golcadomide -

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Basic information

Entry
Database: EMDB / ID: EMD-72652
TitleCereblon-DDB1 with Golcadomide
Map data
Sample
  • Complex: Cereblon-DDB1 with Golcadomide
KeywordsLiganded Cereblon Ligase Closed / LIGASE
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.0 Å
AuthorsWatson ER / Lander GC
Funding support United States, 1 items
OrganizationGrant numberCountry
Other private United States
CitationJournal: Blood Cancer Discov / Year: 2026
Title: Golcadomide: An Oral CELMoD Agent Targeting IKZF1/3 for Diffuse Large B-cell Lymphoma.
Authors: Zhongying Mo / Lynda Groocock / Scott Wood / Diana Jankeel / Derek Mendy / Edmond R Watson / Yan Kai / Gauri Deb / Marjorie Cote / Preethi Janardhanan / Álvaro Fernández-Deudero / Leo ...Authors: Zhongying Mo / Lynda Groocock / Scott Wood / Diana Jankeel / Derek Mendy / Edmond R Watson / Yan Kai / Gauri Deb / Marjorie Cote / Preethi Janardhanan / Álvaro Fernández-Deudero / Leo Barnes / Sophie Peng / Matthew Groza / Evgenia Kalashnikova / Michael Angelo / Jinyi Zhu / Ryan Galasso / In Sock Jang / Manuel Sanchez Castillo / Celia Fontanillo / Geraldine Polido / Andy Christoforou / Timothy Kercher / Gabriel C Lander / Kai Wang / Rama Krishna Narla / Soraya Carrancio / Daniel W Pierce / Mark Rolfe / Neil Bence / Antonia Lopez-Girona /
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 ...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.
SIGNIFICANCE: Golcadomide is an oral cereblon-modulating agent for the treatment of DLBCL. It exhibited rapid, deep, and sustained degradation of IKZF1 and IKZF3, preferentially accumulated in ...SIGNIFICANCE: Golcadomide is an oral cereblon-modulating agent for the treatment of DLBCL. It exhibited rapid, deep, and sustained degradation of IKZF1 and IKZF3, preferentially accumulated in lymphoma residence tissues, and delivered robust antitumor activity. These results provide a strong rationale for continued clinical investigation of golcadomide for patients with DLBCL.
History
DepositionSep 9, 2025-
Header (metadata) releaseOct 15, 2025-
Map releaseOct 15, 2025-
UpdateApr 29, 2026-
Current statusApr 29, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_72652.png

Downloads & links

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Map

FileDownload / File: emd_72652.map.gz / Format: CCP4 / Size: 42.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
1.15 Å/pix.
x 224 pix.
= 257.6 Å		1.15 Å/pix.
x 224 pix.
= 257.6 Å		1.15 Å/pix.
x 224 pix.
= 257.6 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.15 Å
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Contour LevelBy AUTHOR: 0.36
Minimum - Maximum-2.3528204 - 3.0785177
Average (Standard dev.)-0.0012028125 (±0.07735029)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions224224224
Spacing224224224
CellA=B=C: 257.6 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: #1

Fileemd_72652_additional_1.map
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Half map: #2

Fileemd_72652_half_map_1.map
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Half map: #1

Fileemd_72652_half_map_2.map
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Sample components

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Entire : Cereblon-DDB1 with Golcadomide

EntireName: Cereblon-DDB1 with Golcadomide
Components
  • Complex: Cereblon-DDB1 with Golcadomide

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Supramolecule #1: Cereblon-DDB1 with Golcadomide

SupramoleculeName: Cereblon-DDB1 with Golcadomide / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration0.5 mg/mL
BufferpH: 7
VitrificationCryogen name: NITROGEN

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Electron microscopy

MicroscopeFEI TALOS ARCTICA
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.0 µm
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 4.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 1513128
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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