5A2S

Potent, selective and CNS-penetrant tetrasubstituted cyclopropane class IIa histone deacetylase (HDAC) inhibitors

Summary for 5A2S

• Entry DOI: 10.2210/pdb5a2s/pdb
• Descriptor: HISTONE DEACETYLASE 4, (1S,2S,3S)-1-fluoranyl-2-[4-(5-fluoranylpyrimidin-2-yl)phenyl]-N-oxidanyl-3-phenyl-cyclopropane-1-carboxamide, ZINC ION, ... (5 entities in total)
• Functional Keywords: hydrolase, class iia hdac inhibitors, hydroxamic acid, cns exposure, tetrasubstituted cyclopropane, cyclopropanation, huntington's disease
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Nucleus: P56524
• Total number of polymer chains: 2
• Total formula weight: 86553.43

Authors

Luckhurst, C.A.,Breccia, P.,Stott, A.J.,Aziz, O.,Birch, H.,Burli, R.W.,Hughes, S.,Jarvis, R.E.,Lamers, M.,Leonard, P.,Matthews, K.L.,McAllister, G.,Pollack, S.,Saville-Stones, E.,Wishart, G.,Yates, D.,Dominguez, C. (deposition date: 2015-05-22, release date: 2016-02-10, Last modification date: 2024-01-10)

Primary citation

Luckhurst, C.A.,Breccia, P.,Stott, A.J.,Aziz, O.,Birch, H.L.,Burli, R.W.,Hughes, S.J.,Jarvis, R.E.,Lamers, M.,Leonard, P.M.,Matthews, K.L.,Mcallister, G.,Pollack, S.,Saville-Stones, E.,Wishart, G.,Yates, D.,Dominguez, C.
Potent, Selective, and Cns-Penetrant Tetrasubstituted Cyclopropane Class Iia Histone Deacetylase (Hdac) Inhibitors.
Acs Med.Chem.Lett., 7:34-, 2016

PubMed Abstract: Potent and selective class IIa HDAC tetrasubstituted cyclopropane hydroxamic acid inhibitors were identified with high oral bioavailability that exhibited good brain and muscle exposure. Compound 14 displayed suitable properties for assessment of the impact of class IIa HDAC catalytic site inhibition in preclinical disease models.

PubMed: 26819662
DOI: 10.1021/ACSMEDCHEMLETT.5B00302

Experimental method

X-RAY DIFFRACTION (2.65 Å)