5KYJ

Brain penetrant liver X receptor (LXR) modulators based on a 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole core

Summary for 5KYJ

• Entry DOI: 10.2210/pdb5kyj/pdb
• Related: 5I4V 5KYA
• Descriptor: Oxysterols receptor LXR-beta, Retinoic acid receptor RXR-beta, (6~{R})-5-(5-fluoranyl-2-methoxy-pyrimidin-4-yl)-2-(3-methylsulfonylphenyl)-6-propan-2-yl-4,6-dihydropyrrolo[3,4-c]pyrazole, ... (4 entities in total)
• Functional Keywords: dna binding protein, nuclear receptors, liver x receptor, retinoic acid x receptor, lxrbeta-lbd/rxrbeta-lbd heterodimer, chemical modulators
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus : P55055 P28702
• Total number of polymer chains: 4
• Total formula weight: 122281.91

Authors

Chen, G.,McKeever, B.M. (deposition date: 2016-07-21, release date: 2016-09-21, Last modification date: 2023-10-04)

Primary citation

Tice, C.M.,Noto, P.B.,Fan, K.Y.,Zhao, W.,Lotesta, S.D.,Dong, C.,Marcus, A.P.,Zheng, Y.J.,Chen, G.,Wu, Z.,Van Orden, R.,Zhou, J.,Bukhtiyarov, Y.,Zhao, Y.,Lipinski, K.,Howard, L.,Guo, J.,Kandpal, G.,Meng, S.,Hardy, A.,Krosky, P.,Gregg, R.E.,Leftheris, K.,McKeever, B.M.,Singh, S.B.,Lala, D.,McGeehan, G.M.,Zhuang, L.,Claremon, D.A.
Brain penetrant liver X receptor (LXR) modulators based on a 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole core.
Bioorg.Med.Chem.Lett., 26:5044-5050, 2016

PubMed Abstract: Liver X receptor (LXR) agonists have been reported to lower brain amyloid beta (Aβ) and thus to have potential for the treatment of Alzheimer's disease. Structure and property based design led to the discovery of a series of orally bioavailable, brain penetrant LXR agonists. Oral administration of compound 18 to rats resulted in significant upregulation of the expression of the LXR target gene ABCA1 in brain tissue, but no significant effect on Aβ levels was detected.

PubMed: 27599745
DOI: 10.1016/j.bmcl.2016.08.089

Experimental method

X-RAY DIFFRACTION (2.8 Å)