5LPM

Crystal structure of the bromodomain of human Ep300 bound to the inhibitor XDM3d

Summary for 5LPM

• Entry DOI: 10.2210/pdb5lpm/pdb
• Related: 5NRW
• Descriptor: Histone acetyltransferase p300, ~{N}-[(1~{S},2~{S})-7-chloranyl-2-oxidanyl-1,2,3,4-tetrahydronaphthalen-1-yl]-4-ethanoyl-3-ethyl-5-methyl-1~{H}-pyrrole -2-carboxamide, ACETATE ION, ... (4 entities in total)
• Functional Keywords: bromodomain, protein-inhibitor complex, epigenetics, transcription
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: Q09472
• Total number of polymer chains: 2
• Total formula weight: 29330.17

Authors

Huegle, M.,Wohlwend, D.,Gerhardt, S. (deposition date: 2016-08-13, release date: 2017-08-16, Last modification date: 2024-05-01)

Primary citation

Hugle, M.,Lucas, X.,Ostrovskyi, D.,Regenass, P.,Gerhardt, S.,Einsle, O.,Hau, M.,Jung, M.,Breit, B.,Gunther, S.,Wohlwend, D.
Beyond the BET Family: Targeting CBP/p300 with 4-Acyl Pyrroles.
Angew. Chem. Int. Ed. Engl., 56:12476-12480, 2017

PubMed Abstract: Bromodomain and extra-terminal domain (BET) inhibitors are widely used both as chemical tools to study the biological role of their targets in living organisms and as candidates for drug development against several cancer variants and human disorders. However, non-BET bromodomains such as those in p300 and CBP are less studied. XDM-CBP is a highly potent and selective inhibitor for the bromodomains of CBP and p300 derived from a pan-selective BET BRD-binding fragment. Along with X-ray crystal-structure analysis and thermodynamic profiling, XDM-CBP was used in screenings of several cancer cell lines in vitro to study its inhibitory potential on cancer cell proliferation. XDM-CBP is demonstrated to be a potent and selective CBP/p300 inhibitor that acts on specific cancer cell lines, in particular malignant melanoma, breast cancer, and leukemia.

PubMed: 28766825
DOI: 10.1002/anie.201705516

Experimental method

X-RAY DIFFRACTION (1.5 Å)