biostudies-literatureZhang ZNIA NIH HHSNIDDK NIH HHSNCI NIH HHSNINDS NIH HHSNational Institutes of Health2701-2704https://www.ebi.ac.uk/biostudies/studies/S-EPMC6119633biostudies-literatureUnknown28(16)KU-596 is a second-generation C-terminal heat shock protein 90 KDa (Hsp90) modulator based on the natural product, novobiocin. KU-596 has been shown to induce Hsp70 levels and manifest neuroprotective activity through induction of the heat shock response. A ring-constrained analog of KU-596 was designed and synthesized to probe its binding orientation and ability to induce Hsp70 levels. Compound 2 was found to exhibit comparable or increased activity compared to KU-596, which is under clinical investigation for the treatment of neuropathy.Bioorganic & medicinal chemistry lettersSynthesis and evaluation of a ring-constrained Hsp90 C-terminal inhibitor that exhibits neuroprotective activity.PMC6119633U01 CA120458NS075311P30 AG035982R01 NS075311DK095911R01 DK095911CA120458R01 CA120458You ZDobrowsky RTZhang ZBlagg BSJfalseSynthesis and evaluation of a ring-constrained Hsp90 C-terminal inhibitor that exhibits neuroprotective activity.KU-596 is a second-generation C-terminal heat shock protein 90 KDa (Hsp90) modulator based on the natural product, novobiocin. KU-596 has been shown to induce Hsp70 levels and manifest neuroprotective activity through induction of the heat shock response. A ring-constrained analog of KU-596 was designed and synthesized to probe its binding orientation and ability to induce Hsp70 levels. Compound 2 was found to exhibit comparable or increased activity compared to KU-596, which is under clinical investigation for the treatment of neuropathy.2018-01-01T00:00:00Z2018 Sep2024-11-11T21:09:06.901Z2019-09-04T07:02:06ZS-EPMC61196332975972810.1016/j.bmcl.2018.03.071