PDBsum entry 4zom

Transcription

PDB id: 4zom

Contents

Protein chains

223 a.a.

Ligands

4Q3 ×4

Waters ×48

PDB id:

4zom

Name:

Transcription

Title:

Rorgamma in complex with inverse agonist 4j.

Structure:

Nuclear receptor ror-gamma. Chain: a, b, c, d. Fragment: ligand binding domain. Synonym: nuclear receptor rzr-gamma,nuclear receptor subfamily 1 group f member 3,rar-related orphan receptor c,retinoid-related orphan receptor-gamma. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: rorc, nr1f3, rorg, rzrg. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.27Å R-factor: 0.202 R-free: 0.240

Authors:

D.J.Marcotte

Key ref:

T.Wang et al. (2015). Discovery of novel pyrazole-containing benzamides as potent RORγ inverse agonists. Bioorg Med Chem Lett, 25, 2985-2990. PubMed id: 26048789 DOI: 10.1016/j.bmcl.2015.05.028

Date:

06-May-15 Release date: 17-Jun-15

Protein chains

P51449  (RORG_HUMAN) -  Nuclear receptor ROR-gamma from Homo sapiens

Seq: 518 a.a.

Struc: 223 a.a.

DOI no: 10.1016/j.bmcl.2015.05.028

Bioorg Med Chem Lett 25:2985-2990 (2015)

PubMed id: 26048789

Discovery of novel pyrazole-containing benzamides as potent RORγ inverse agonists.

T.Wang, D.Banerjee, T.Bohnert, J.Chao, I.Enyedy, J.Fontenot, K.Guertin, H.Jones, E.Y.Lin, D.Marcotte, T.Talreja, K.Van Vloten.

ABSTRACT

The nuclear receptor RORγ plays a central role in controlling a pro-inflammatory gene expression program in several lymphocyte lineages including TH17 cells. RORγ-dependent inflammation has been implicated in the pathogenesis of several major autoimmune diseases and thus RORγ is an attractive target for therapeutic intervention in these diseases. Starting from a lead biaryl compound 4a, replacement of the head phenyl moiety with a substituted aminopyrazole group resulted in a series with improved physical properties. Further SAR exploration led to analogues (e.g., 4j and 5m) as potent RORγ inverse agonists.