YM-1 is stable and soluble MKT-077.MKT-077 analogs and orally bioactive Hsp70 inhibitors. YM-1 induces HeLa cell death and upregulates the protein levels of p53 and p21.

Physicochemical Properties

Molecular Formula	C20H20CLN3OS2
Molecular Weight	417.98
Exact Mass	417.073
CAS #	409086-68-6
Related CAS #	HSP70-IN-4;1427450-47-2
PubChem CID	10895023
Appearance	Brown to reddish brown solid powder
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	2
Heavy Atom Count	27
Complexity	633
Defined Atom Stereocenter Count	0
SMILES	CCN1/C(=C/C2=CC=CC=[N+]2C)/S/C(=C/3\N(C4=CC=CC=C4S3)C)/C1=O.[Cl-]
InChi Key	KEQDCNWQIQWINZ-KPJFUTMLSA-M
InChi Code	InChI=1S/C20H20N3OS2.ClH/c1-4-23-17(13-14-9-7-8-12-21(14)2)26-18(19(23)24)20-22(3)15-10-5-6-11-16(15)25-20;/h5-13H,4H2,1-3H3;1H/q+1;/p-1/b20-18+;
Chemical Name	(2Z,5E)-3-ethyl-5-(3-methyl-1,3-benzothiazol-2-ylidene)-2-[(1-methylpyridin-1-ium-2-yl)methylidene]-1,3-thiazolidin-4-one;chloride
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	YM-1 inhibits a portion of the Nnos' ability to bind to ATP via promoting Hsp70-dependent phases in the maturation process [1]. YM-1 (0-200 μM) stimulates Hsp70 binding to substrates that are unfolded [1]. Hsp70 is transformed into a tight affinity conformation by YM-1 (0.001-1000 μM), and the IC50 value for binding to Hsp70 is 8.2 μM[1]. In a 24-hour period, YM-1 (0, 0.1, 0.5, and 1 μM) increases nNOS ubiquitination [1]. YM-1 (10 μM; 48 hours) upregulates p53 and p21 and downregulates the protein levels of FoxM1 and survivin. YM-1 (5 and 10 μM; 24 and 48 hours) promotes HeLa cell death and hTERT-RPE1 cell growth arrest [2]. [2].
ln Vivo	Through the activation of Hsp70, YM-1 (1 mM; orally, for 7 days) protects Drosophila from polyQ poisoning [1].
Cell Assay	Western Blot Analysis[2] Cell Types: HeLa and hTERT-RPE1 cell lines Tested Concentrations: 10 μM Incubation Duration: 48 hrs (hours)I Experimental Results: Increased the level of p53 and p21 and diminished the level of FoxM1 and survivin.
Animal Protocol	Animal/Disease Models: UAS-hAR52Q flies with polyQ AR-induced dihydrotestosterone (DHT) phenotype[1] Doses: 1 mM Route of Administration: Oral administration; 1 mM, for 7 days Experimental Results: Weakened the DHT-dependent eye degeneration phenotype and rescued DHT-dependent pupal toxicity of the polyQ AR.
References	[1]. Activation of Hsp70 reduces neurotoxicity by promoting polyglutamine protein degradation. Nat Chem Biol. 2013 Feb;9(2):112-8. [2]. Effect of an Inhibitor of HSP70, YM-1, on Hikeshi Knockout Cells. Thermal Medicine. 2017, 33(4):129-134.

Solubility Data

Solubility (In Vitro)

H2O : 50 mg/mL (119.62 mM) DMSO : 30 mg/mL (71.77 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.98 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.98 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3925 mL	11.9623 mL	23.9246 mL
	5 mM	0.4785 mL	2.3925 mL	4.7849 mL
	10 mM	0.2392 mL	1.1962 mL	2.3925 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.