Biochem/physiol Actions

Reversible: yes

Cell permeable: yes

Primary TargetHSP70

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, 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).

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.

Legal Information

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

Other Notes

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

Packaging

Packaged under inert gas

Reconstitution

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

Warning

Toxicity: Standard Handling (A)