5CJ6

Crystal Structure of a Selective Androgen Receptor Modulator Bound to the Ligand Binding Domain of the Human Androgen Receptor

Summary for 5CJ6

• Entry DOI: 10.2210/pdb5cj6/pdb
• Descriptor: Androgen receptor, small peptide, 2-chloro-4-{[(1R,2R)-2-hydroxy-2-methylcyclopentyl]amino}-3-methylbenzonitrile, ... (4 entities in total)
• Functional Keywords: androgen receptor, nuclear hormone receptor, signaling protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus: P10275
• Total number of polymer chains: 2
• Total formula weight: 34063.79

Authors

Luz, J.G.,Saeed, A.,Wang, Y. (deposition date: 2015-07-14, release date: 2016-01-06, Last modification date: 2024-03-06)

Primary citation

Saeed, A.,Vaught, G.M.,Gavardinas, K.,Matthews, D.,Green, J.E.,Losada, P.G.,Bullock, H.A.,Calvert, N.A.,Patel, N.J.,Sweetana, S.A.,Krishnan, V.,Henck, J.W.,Luz, J.G.,Wang, Y.,Jadhav, P.
2-Chloro-4-[[(1R,2R)-2-hydroxy-2-methyl-cyclopentyl]amino]-3-methyl-benzonitrile: A Transdermal Selective Androgen Receptor Modulator (SARM) for Muscle Atrophy.
J.Med.Chem., 59:750-755, 2016

PubMed Abstract: A transdermal SARM has a potential to have therapeutic benefit through anabolic activity in muscle while sparing undesired effects of benign prostate hyperplasia (BPH) and liver-mediated decrease in HDL-C. 2-Chloro-4-[(2-hydroxy-2-methyl-cyclopentyl)amino]-3-methyl-benzonitrile 6 showed the desired muscle and prostate effects in a preclinical ORX rat model. Compound 6 had minimal effect on HDL-C levels in cynomolgus monkeys and showed human cadaver skin permeability, thus making it an effective tool for proof-of-concept studies in a clinical setting.

PubMed: 26683992
DOI: 10.1021/acs.jmedchem.5b01168

Experimental method

X-RAY DIFFRACTION (2.07 Å)