6ffg

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Human BRD2 C-terminal bromodomain with (S)-1-(2-cyclopropyl-4-(2-(hydroxymethyl)benzyl)-6-(1,2,3,6-tetrahydropyridin-4-yl)-3,4-dihydroquinoxalin-1(2H)-yl)ethanone

Structural highlights

6ffg is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.59Å
Ligands:D7B, EDO, MES, PEG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BRD2_HUMAN May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.[1]

Publication Abstract from PubMed

The bromodomain and extra-terminal domain (BET) family of proteins bind acetylated lysine residues on histone proteins. The four BET bromodomains-BRD2, BRD3, BRD4, and BRDT-each contain two bromodomain modules. BET bromodomain inhibition is a potential therapy for various cancers and immunoinflammatory diseases, but few reported inhibitors show selectivity within the BET family. Inhibitors with selectivity for the first or second bromodomain are desired to aid investigation of the biological function of these domains. Focused library screening identified a series of tetrahydroquinoxalines with selectivity for the second bromodomains of the BET family (BD2). Structure-guided optimization of the template improved potency, selectivity, and physicochemical properties, culminating in potent BET inhibitors with BD2 selectivity.

Discovery of Tetrahydroquinoxalines as Bromodomain and Extra-Terminal Domain (BET) Inhibitors with Selectivity for the Second Bromodomain.,Law RP, Atkinson SJ, Bamborough P, Chung CW, Demont EH, Gordon LJ, Lindon M, Prinjha RK, Watson AJB, Hirst DJ J Med Chem. 2018 May 24;61(10):4317-4334. doi: 10.1021/acs.jmedchem.7b01666. Epub, 2018 May 3. PMID:29656650[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. ↑ LeRoy G, Rickards B, Flint SJ. The double bromodomain proteins Brd2 and Brd3 couple histone acetylation to transcription. Mol Cell. 2008 Apr 11;30(1):51-60. doi: 10.1016/j.molcel.2008.01.018. PMID:18406326 doi:10.1016/j.molcel.2008.01.018
  2. ↑ Law RP, Atkinson SJ, Bamborough P, Chung CW, Demont EH, Gordon LJ, Lindon M, Prinjha RK, Watson AJB, Hirst DJ. Discovery of Tetrahydroquinoxalines as Bromodomain and Extra-Terminal Domain (BET) Inhibitors with Selectivity for the Second Bromodomain. J Med Chem. 2018 May 24;61(10):4317-4334. doi: 10.1021/acs.jmedchem.7b01666. Epub, 2018 May 3. PMID:29656650 doi:http://dx.doi.org/10.1021/acs.jmedchem.7b01666

Contents


PDB ID 6ffg

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