3DCT

FXR with SRC1 and GW4064

Summary for 3DCT

• Entry DOI: 10.2210/pdb3dct/pdb
• Related: 3DCU
• Descriptor: Bile acid receptor, Nuclear receptor coactivator 1, 3-[(E)-2-(2-chloro-4-{[3-(2,6-dichlorophenyl)-5-(1-methylethyl)isoxazol-4-yl]methoxy}phenyl)ethenyl]benzoic acid, ... (4 entities in total)
• Functional Keywords: fxr, nuclear receptor, gw4064, alpha-helical sandwich, activator, alternative splicing, dna-binding, metal-binding, nucleus, receptor, repressor, transcription regulation, zinc, zinc-finger, acyltransferase, chromosomal rearrangement, phosphoprotein, polymorphism, proto-oncogene, transferase, ubl conjugation, transcription-transcription activator complex, transcription/transcription activator
• 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: 2
• Total formula weight: 30702.46

Authors

Williams, S.P.,Madauss, K.P. (deposition date: 2008-06-04, release date: 2008-08-12, Last modification date: 2023-08-30)

Primary citation

Akwabi-Ameyaw, A.,Bass, J.Y.,Caldwell, R.D.,Caravella, J.A.,Chen, L.,Creech, K.L.,Deaton, D.N.,Jones, S.A.,Kaldor, I.,Liu, Y.,Madauss, K.P.,Marr, H.B.,McFadyen, R.B.,Miller, A.B.,III, F.N.,Parks, D.J.,Spearing, P.K.,Todd, D.,Williams, S.P.,Wisely, G.B.
Conformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid-based analogs of GW 4064.
Bioorg.Med.Chem.Lett., 18:4339-4343, 2008

PubMed Abstract: Starting from the known FXR agonist GW 4064 1a, a series of stilbene replacements were prepared. The 6-substituted 1-naphthoic acid 1b was an equipotent FXR agonist with improved developability parameters relative to 1a. Analog 1b also reduced the severity of cholestasis in the ANIT acute cholestatic rat model.

PubMed: 18621523
DOI: 10.1016/j.bmcl.2008.06.073

Experimental method

X-RAY DIFFRACTION (2.5 Å)