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5.00615

Sigma-Aldrich

Hsp70 Activator, YM-1

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Synonym(s):
Hsp70 Activator, YM-1, YM-01, Heat Shock 70 kDa Protein Activator, Hsp70 Chemical Co-Chaperone, YM1, YM01, 2-((Z)-((E)-3-ethyl-5-(3-methylbenzo[d]thiazol-2(3H)-ylidene)-4-oxothiazolidin-2-ylidene)methyl)-1-methylpyridin-1-ium chloride, 2-[3-Ethyl-5-(3-methyl-3H-benzothiazol-2-, YM-01, Heat Shock 70 kDa Protein Activator, Hsp70 Chemical Co-Chaperone, YM1, YM01, 2-((Z)-((E)-3-ethyl-5-(3-methylbenzo[d]thiazol-2(3H)-ylidene)-4-oxothiazolidin-2-ylidene)methyl)-1-methylpyridin-1-ium chloride, 2-[3-Ethyl-5-(3-methyl-3H-benzothiazol-2-y
Empirical Formula (Hill Notation):
C20H19N3OS2 · xHCl
Molecular Weight:
381.51 (free base basis)

Assay

≥98% (HPLC)

Quality Level

form

solid

manufacturer/tradename

Calbiochem®

storage condition

OK to freeze
protect from light

color

orange-red

solubility

DMSO: 10 mg/mL

storage temp.

−20°C

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This Item
MABE1120RAB0216SAB56000333
form

solid

form

-

form

-

form

-

manufacturer/tradename

Calbiochem®

manufacturer/tradename

-

manufacturer/tradename

-

manufacturer/tradename

-

storage condition

OK to freeze, protect from light

storage condition

-

storage condition

-

storage condition

-

color

orange-red

color

-

color

-

color

-

solubility

DMSO: 10 mg/mL

solubility

-

solubility

-

solubility

-

General description

A cell-permeable rhodacyanine derivative that stabilizes Hsp70 (heat-shock protein 70) in its ADP-bound, substrate-binding conformation via reversible binding to Hsp70 nucleotide-binding domain (KD = 4.9 µM using YM-1-biotin) in a manner similar to the physiological Hsp70 co-chaperone Hip and YM-1 is shown to compete against Hip for Hsp70 binding. Both Hip overexpression and YM-1 treatment are shown to enhance cellular nNOS ubiquitination (2.57-fold of DMSO control monoUb nNOS level; 1 µM for 24 h) in nNOS-expressing HEK293 cells and promote proteasomal clearance of AR (androgen receptor) ligand-induced accumulation of unfolded AR112Q aggregates (by 35% with 1 µM YM-1 treatment for 72 h post 4 h 10 nM R1881 induction) in polyQ AR-expressing PC12 cultures. Likewise, YM-1, when co-supplemented with AR ligand dihydrotestosterone in food (1 mM each), reduces DHT-induced toxicity in transgenic Drosophila expressing human polyQ AR AR52Q as assessed by the severeness of rough eye phenotype and pupal eclosion rate. Also reported to downregulate Akt1/2 level in MCF7 cancer cells in a dose-dependent manner (by 53% with 6 h 10 µM treatment) and sensitize 4-OHT- (Cat. No. 479002) resistant TR-MCF7 to proliferation inhibition by 4-OHT in MTT assays (by 55%; 4 h 10 µM YM-1 alone prior to 44 h 10 µM 4-OHT treatment alone).
A stable and soluble MKT-077 analog that acts an allosteric activator of heat-shock protein 70 (HSP70). Its action appears to be similar to HSP70 interacting protein (HIP). Shown to convert HSP70 to its tight-affinity conformation and promote the accumulation of the ADP-bound form of HSP70. Increases the binding of HSP70 to its unfolded substrates . Also shown to enhance ubiquitination and degradation of nNOS and polyglutamine androgen receptor (polyQ AR) (at ~1 mM). Displays selective cytotoxicity across multiple cancer cell lines without affecting the normal cells. Also reported to restore tamoxifen sensitivity to a refractory tamoxifen-resistant MCF7 cells (~10 mM).

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

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

Abisambra, J. et al. 2013. Biol. Psychiatry74, 367.
Miyata, Y., et al. 2013. ACS Chem. Neurosci.4, 930.
Wang, A.M., et al. 2013. Nat. Chem. Biol.9, 112.
Koren, J. 3rd, et al. 2012. PLoS. One.7, e35566.
Rousaki, A., et al. 2011. J. Mol. Biol.411, 614.

Legal Information

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

Storage Class Code

11 - Combustible Solids

WGK

WGK 3

Flash Point(F)

Not applicable

Flash Point(C)

Not applicable


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