Cemdomespib  (Synonyms: KU-596)

Cemdomespib (KU-596) is a highly bioavailable second-generation Hsp90 modulator. Cemdomespib has shown efficacy in improving sensory deficits in models of diabetic peripheral neuropathy. Cemdomespib induces Hsp70 levels and manifest neuroprotective activity through induction of the heat shock response^[1][2][3].

After 8 weeks of diabetes, Cemdomespib (KU-596; 2, 10, or 20 mg/kg ; i.p.; administered for 6 weeks via a once per week) dose-dependently reverses the pre-existing psychosensory deficits. Cemdomespib also dose-dependently prevents the diabetes-induced deficits in motor (MNCV) and sensory (SNCV) nerve conduction velocities^[1].
Cemdomespib (20 mg/kg; oral gavage once per week for 4 weeks) significantly reverses the sensory hypoalgesia in WT mice but not the Hsp70 KO mice^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

447.50

C₂₄H₃₀FNO₆

1450642-92-8

CC(NCCC1=C(C2=CC(F)=CC=C2)C=C(C=C1)O[C@H]3[C@@H]([C@@H]([C@H](C(C)(O3)C)OC)O)O)=O

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• [1]. Jiacheng Ma, et al. Modulating Molecular Chaperones Improves Mitochondrial Bioenergetics and Decreases the Inflammatory Transcriptome in Diabetic Sensory Neurons. ACS Chem Neurosci. 2015 Sep 16;6(9):1637-48.  [Content Brief]

  [2]. Xinyue Zhang, et al. Targeting Heat Shock Protein 70 to Ameliorate c-Jun Expression and Improve Demyelinating Neuropathy. ACS Chem Neurosci. 2018 Feb 21;9(2):381-390.  [Content Brief]

  [3]. Zheng Zhang, et al. 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.  [Content Brief]