2. Academic Validation
  3. Synthesis and evaluation of a ring-constrained Hsp90 C-terminal inhibitor that exhibits neuroprotective activity

Synthesis and evaluation of a ring-constrained Hsp90 C-terminal inhibitor that exhibits neuroprotective activity

  • Bioorg Med Chem Lett. 2018 Sep 1;28(16):2701-2704. doi: 10.1016/j.bmcl.2018.03.071.
Zheng Zhang 1,  Zhenyuan You 2,  Rick T Dobrowsky 2,  Brian S J Blagg 3
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, The University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556, United States.
  • 2 Department of Pharmacology and Toxicology Department, The University of Kansas, Lawrence, KS 66045, United States.
  • 3 Department of Chemistry and Biochemistry, The University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556, United States. Electronic address: [email protected].
PMID: 29759728 DOI: 10.1016/j.bmcl.2018.03.071
Abstract

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.

Keywords

Hsp90 C-terminal inhibitor; Neuroprotective; Novologue; Ring-constrained.

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