3OMM

Crystal structure of human FXR in complex with 4-({(2S)-2-[2-(4-chlorophenyl)-5,6-difluoro-1H-benzimidazol-1-yl]-2-cyclohexylacetyl}amino)-3-fluorobenzoic acid

Summary for 3OMM

• Entry DOI: 10.2210/pdb3omm/pdb
• Related: 3OKH 3OKI 3OLF 3OMK 3OOF 3OOK
• Descriptor: Bile acid receptor, peptide of Nuclear receptor coactivator 1, 4-({(2S)-2-[2-(4-chlorophenyl)-5,6-difluoro-1H-benzimidazol-1-yl]-2-cyclohexylacetyl}amino)-3-fluorobenzoic acid, ... (4 entities in total)
• Functional Keywords: nuclear receptor, cholesterol, bile acid, dna-binding, nucleus, receptor, transcription, ligand binding domain transcription regulation, coactivator, fxr alternative splicing, hormone receptor
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus . Isoform 1: Nucleus . Isoform 2: Nucleus . Isoform 3: Nucleus . Isoform 4: Nucleus : Q96RI1; Nucleus : Q15788
• Total number of polymer chains: 4
• Total formula weight: 58864.33

Authors

Rudolph, M.G. (deposition date: 2010-08-27, release date: 2011-01-19, Last modification date: 2024-04-03)

Primary citation

Richter, H.G.F.,Benson, G.M.,Bleicher, K.H.,Blum, D.,Chaput, E.,Clemann, N.,Feng, S.,Gardes, C.,Grether, U.,Hartman, P.,Kuhn, B.,Martin, R.E.,Plancher, J.M.,Rudolph, M.G.,Schuler, F.,Taylor, S.
Optimization of a novel class of benzimidazole-based farnesoid X receptor (FXR) agonists to improve physicochemical and ADME properties
Bioorg.Med.Chem.Lett., 21:1134-1140, 2011

PubMed Abstract: Structure-guided lead optimization of recently described benzimidazolyl acetamides addressed the key liabilities of the previous lead compound 1. These efforts culminated in the discovery of 4-{(S)-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-acetylamino}-3-fluoro-benzoic acid 7g, a highly potent and selective FXR agonist with excellent physicochemical and ADME properties and potent lipid lowering activity after oral administration to LDL receptor deficient mice.

PubMed: 21269824
DOI: 10.1016/j.bmcl.2010.12.123

Experimental method

X-RAY DIFFRACTION (2.1 Å)