PDBsum entry 4akn

Protein binding

PDB id: 4akn

Contents

Protein chain

112 a.a.

Ligands

EDO

S5B ×2

SO4 ×3

DMS

Waters ×333

PDB id:

4akn

Name:

Protein binding

Title:

N-terminal bromodomain of human brd2 with tbutyl-phenyl-amino- dimethyl-oxazolyl-quinoline-carboxylic acid

Structure:

Bromodomain-containing protein 2. Chain: a, b, c. Fragment: residues 67-200. Synonym: o27.1.1, really interesting new gene 3 protein human brd2. Engineered: yes

Source:

Homo sapiens. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.82Å R-factor: 0.170 R-free: 0.197

Authors:

C.Chung,Y.Lamotte,F.Donche,A.Bouillot,O.Mirguet

Key ref:

J.Seal et al. (2012). Identification of a novel series of BET family bromodomain inhibitors: binding mode and profile of I-BET151 (GSK1210151A). Bioorg Med Chem Lett, 22, 2968-2972. PubMed id: 22437115

Date:

26-Feb-12 Release date: 04-Jul-12

Protein chains

P25440  (BRD2_HUMAN) -  Bromodomain-containing protein 2 from Homo sapiens

Seq: 801 a.a.

Struc: 112 a.a.

Enzyme reactions

• Enzyme class: E.C.?

Bioorg Med Chem Lett 22:2968-2972 (2012)

PubMed id: 22437115

Identification of a novel series of BET family bromodomain inhibitors: binding mode and profile of I-BET151 (GSK1210151A).

J.Seal, Y.Lamotte, F.Donche, A.Bouillot, O.Mirguet, F.Gellibert, E.Nicodeme, G.Krysa, J.Kirilovsky, S.Beinke, S.McCleary, I.Rioja, P.Bamborough, C.W.Chung, L.Gordon, T.Lewis, A.L.Walker, L.Cutler, D.Lugo, D.M.Wilson, J.Witherington, K.Lee, R.K.Prinjha.

ABSTRACT

A novel series of quinoline isoxazole BET family bromodomain inhibitors are discussed. Crystallography is used to illustrate binding modes and rationalize their SAR. One member, I-BET151 (GSK1210151A), shows good oral bioavailability in both the rat and minipig as well as demonstrating efficient suppression of bacterial induced inflammation and sepsis in a murine in vivo endotoxaemia model.