5.05276

HSP70 Activator II, YM-08

• Synonym(s): HSP70 Activator II, YM-08, (2Z,5E)-3-ethyl-5-(3-methylbenzo[d]thiazol-2(3H)-ylidene)-2-(pyridin-2-ylmethylene)thiazolidin-4-one, Heat Shock 70 kDa Protein Activator II, Hsp70 Chemical Co-Chaperone II, YM-08, YM08, YM8
• Empirical Formula (Hill Notation): C₁₉H₁₇N₃OS₂
• CAS Number: 1427472-76-1
• Molecular Weight: 367.49
• UNSPSC Code: 12352200
• PubChem Substance ID: 72201046
• NACRES: NA.77

Properties

• assay: ≥99% (HPLC)
• Quality Level: 100
• form: solid
• potency: 0.6 μM IC₅₀
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: orange
• solubility: DMSO: 50 mg/mL
• storage temp.: 2-8°C
• SMILES string: CCN1C(=CC2=CC=CC=N2)SC(=C3N(C4=CC=CC=C4S3)C)C1=O

Description

General description

A cell-permeable, neutrally charged, pyridinium-to-pyridine substituted YM-01 (Cat. No. 500615) and MKT-077 structural analog that exhibits higher HSP70-binding affinity than its cationic pyridinium counterparts (IC₅₀ = 0.61 µM/YM-08, 3.2 µM/YM-01, and 6.4 µM/MKT-077, respectively, in competitive binding assays using human Hsc70/HSPA8), but reduced tau degradation-promoting potency in cultures (% degradation of p-tau/total tau/24 h = 42/64, 88/89, and 81/80 in HeLaC3 with 30 µM YM-08, MKT-077, or YM-01, respectively) and weaker anti-cancer activity (IC₅₀ against MDA-MB-231/MCF10A/MCF7 in µM = 1.4/3.0/2,2/MKT-077, 2.0/3.3/5.2/YM-01, and 8.5/7.8/10.5/YM-08 with 72 h compound treatment). However, only YM-08, but not YM-01 or MKT-077, exhibits detectable blood-brain-barrier permeability in mice (C_max = 4 µg/g; t_1/2 = 6.8 h; AUC_inf = 260 ng·h/g; 6.6 mg/kg via i.v.; 100 µL/mouse in 30% H₂O/5% Cremophor/5% EtOH/60% PBS) with much reduced accumulation in kidney in vivo.

A cell-permeable, neutrally charged, pyridinium-to-pyridine substituted YM-01 (Cat. No. 500615) and MKT-077 structural analog that exhibits higher HSP70-binding affinity, but reduced tau degradation-promoting potency in cultures (% degradation of p-tau/total tau = 42/64, 88/89, and 81/80 in HeLaC3 with 30 µM YM-08, MKT-077, or YM-01, respectively) and weaker anti-cancer activity (IC₅₀ against MDA-MB-231/MCF10A/MCF7 in µM = 1.4/3.0/2,2/MKT-077, 2.0/3.3/5.2/YM-01, and 8.5/7.8/10.5/YM-08 in 72 h).

Biochem/physiol Actions

Cell permeable: yes

Primary Target
HSP70

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Other Notes

Miyata, Y., et al. 2013. ACS Chem. Neurosci.4, 930.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk_germany: WGK 2
• flash_point_f: Not applicable
• flash_point_c: Not applicable