HSP Modulators: YM-01

YM-01 Chemical Structure HSP70 Inhibitors and ModulatorsYM-01

Heat Shock Protein 70/HSP70 Inhibitor

StressMarq catalog# SIH-121

CAS Number: 409086-68-6

Molecular Formula: C20H20ClN3OS2

Molecular Weight: 417.97 g/mol

 

Research Areas: Cancer Research, Heat Shock, Apoptosis, Cell Signalling, Neuroscience, Neurodegeneration, Alzheimer’s

Alternative Names: YM-1, 2-((Z)-((E)-3-ethyl-5-(3-methylbenzo[d]thiazol-2(3H)-ylidene)-4-oxothiazolidin-2-ylidene)methyl)-1-methylpyridin-1-ium chloride, YM01, Heat Shock 70 kDa Protein Activator, Hsp70 Chemical Co-Chaperone, YM1

 

Biological Description

YM-01 is an allosteric Heat shock protein 70 (Hsp70) inhibitor. It binds within the nucleotide binding domain of HSP70, adjacent to ATP/ADP binding pocket. YM-01 inhibits J-stimulated ATP turnover rate. It blocks Hsc70-bag1 interaction both in vitro and in vivo and enhances binding of Hsp70 to misfolded proteins.

YM-01 reduces tau levels in tau-overexpressed HeLa cells, endogenous tau in neuroblastoma cells, and endogenous tau in primary neuron from rTg4510 mice, with EC50’s of low micromolar. It recovers long-term potentiation deficits in brain slices from rTg4510 mice. YM-01 also has anti-cancer activity, with an EC50 value of low micromolar against several cancer cell lines. It destabilizes oncoproteins in cells, including Akt and Raf-1.

 

References:

  1. Wang AM, et al. Activation of Hsp70 reduces neurotoxicity by promoting polyglutamine protein degradation. Nat Chem Biol. 2013;9(2):112-8.
  2. Abisambra J, et al. Allosteric heat shock protein 70 inhibitors rapidly rescue synaptic plasticity deficits by reducing aberrant tau. Biol Psychiatry. 2013;74(5):367-74.
  3. Koren J 3rd, et al. Rhodacyanine Derivative Selectively Targets Cancer Cells and Overcomes Tamoxifen Resistance. PLoS One. 2012;7(4):e35566.
  4. Morishima Y, et al. Heme-dependent activation of neuronal nitric oxide synthase by cytosol is due to an Hsp70-dependent, thioredoxin-mediated thiol-disulfide interchange in the heme/substrate binding cleft. Biochemistry. 2011;50(33):7146-56.
  5. Davis MJ, et al. Inducible renitence limits Listeria monocytogenes escape from vacuoles in macrophages. J Immunol. 2012;189(9):4488-95.