GLPBio

JTV-519 free base

Catalog No.: GC36371Purity:>98%Synonyms: K201 free base
COASDSData Sheet
JTV-519 free base is a Ca2+-dependent blocker of SERCA that inhibits the ATPase activity.

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JTV-519 free base
Cas No.: 145903-06-6
10mM (in 1mL DMSO)In Stock
$56.00
1
5mgIn Stock
$53.00
1
10mgIn Stock
$84.00
1
25mgIn Stock
$175.00
1
50mgIn Stock
$294.00
1
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Description

JTV-519 free base is a Ca2+-dependent blocker of SERCA that inhibits the ATPase activity [1]. JTV-519 free base can inhibit Na+, Ca2+ and K+ currents in guinea-pig ventricular cells, and exhibit cardioprotection against ischaemia/reperfusion injury in isolated rat hearts through the activation of protein kinase C [2]. JTV-519 free base has been widely used to alter the spatiotemporal properties of diastolic Ca2+ release and the associated diastolic contraction in rat ventricular cardiomyocytes [3].

In vitro, JTV-519 free base pretreatment (1μM) for 12 hours stabilized the RyR1 channel in flexor digitorum brevis muscle fibers of mice and reduced the delay in calcium reuptake induced by FK506 [4]. Treatment with 1μM JTV-519 free base for 7 days on HL-1 cells significantly reduced the calcium leak from the sarcoplasmic reticulum caused by hypoxia and increased the expression of the RyR2 gene[5]. The treatment of PC14 cells with 10μM JTV-519 free base for 72 hours significantly increased the platinum level in the cells and enhanced the cytotoxic effect of platinum on the cells[6].

In vivo, JTV-519 free base treatment via intravenous infusion (0.5mg/kg/h) for 2 hours inhibited the leak of cytosolic calcium from the sarcoplasmic reticulum in septic mice and improved cardiac function[7]. Intravenous infusion of JTV-519 free base (0.5mg/kg/h) for 4 weeks significantly improved the cardiac function of the myocardial infarction mouse model and reversed cardiac remodeling[8].

References:
[1] Darcy Y L, Diaz-Sylvester P L, Copello J A. K201 (JTV519) is a Ca2+-dependent blocker of SERCA and a partial agonist of ryanodine receptors in striated muscle[J]. Molecular Pharmacology, 2016, 90(2): 106-115.
[2] Nakaya H, Furusawa Y, Ogura T, et al. Inhibitory effects of JTV‐519, a novel cardioprotective drug, on potassium currents and experimental atrial fibrillation in guinea‐pig hearts[J]. British journal of pharmacology, 2000, 131(7): 1363-1372.
[3] Elliott E B, Hasumi H, Otani N, et al. K201 (JTV-519) alters the spatiotemporal properties of diastolic Ca2+ release and the associated diastolic contraction during β-adrenergic stimulation in rat ventricular cardiomyocytes[J]. Basic research in cardiology, 2011, 106(6): 1009-1022.
[4] Breckner A, Ganz M, Marcellin D, et al. Effect of Calstabin1 depletion on calcium transients and energy utilization in muscle fibers and treatment opportunities with RyR1 stabilizers[J]. PloS one, 2013, 8(11): e81277.
[5] Trinh M D, Fiserova I, Vacek L, et al. Hypoxia-Induced Sarcoplasmic Reticulum Ca2+ Leak Is Reversed by Ryanodine Receptor Stabilizer JTV-519 in HL-1 Cardiomyocytes[J]. Anatolian Journal of Cardiology, 2022, 26(6): 476.
[6] Nakamura T, Koizumi F, Kaneko N, et al. Reversal of Cisplatin Resistance by the 1, 4‐Benzothiazepine Derivative, JTV‐519[J]. Japanese journal of cancer research, 2001, 92(6): 597-602.
[7] Yang J, Zhang R, Jiang X, et al. Toll-like receptor 4–induced ryanodine receptor 2 oxidation and sarcoplasmic reticulum Ca2+ leakage promote cardiac contractile dysfunction in sepsis[J]. Journal of Biological Chemistry, 2018, 293(3): 794-807.
[8] Wehrens X H T, Lehnart S E, Reiken S, et al. Enhancing calstabin binding to ryanodine receptors improves cardiac and skeletal muscle function in heart failure[J]. Proceedings of the National Academy of Sciences, 2005, 102(27): 9607-9612.

Protocol

Cell experiment [1]:

Cell lines

HL-1 cells

Preparation Method

HL-1 cells were grown in DMEM medium with 10% (v/v) fetal bovine serum (FBS), 100μg/ml streptomycin, 100U/ml penicillin, 0.1mM norepinephrine, and 2mM L-glutamine at 37°C in 5% CO2/atmosphere. For hypoxic exposures, cells were placed in the modular chamber incubators and flushed with calibration quality gas mixtures of 1% O2 + 5% CO2 to achieve hypoxic exposures. The cells were treated with 1μM JTV-519 free base for 7 days. Cell viability was evaluated. The expression of the RyR2 gene was analyzed.

Reaction Conditions

1μM; 7 days

Applications

JTV-519 free base treatment significantly promoted RyR2 gene expression in HL-1 cells in hypoxic conditions.
Animal experiment [2]:

Animal models

C57BL/6 mice

Preparation Method

C57BL/6 mice (18-22g) were housed singly in a standard environment with food and water ad libitum. The mice were endotracheally intubated under deep anesthesia with a mixture of pentobarbital sodium (50mg/kg; i.p.). The abdominal cavity was opened, and the distal 1cm of the cecum was ligated with a suture and punctured twice with a needle of 16 gauge. After surgery, all mice received a 1-ml subcutaneous injection of physiological saline. As controls, sham-operated mice received the same procedures except for ligation and puncture. JTV-519 free base (0.5mg/kg/h) was applied intraperitoneally 2h before the surgery. The hearts of the mice were collected for analysis.

Dosage form

0.5mg/kg/h; 2h; i.v.

Applications

JTV-519 free base treatment significantly improved cardiac function in mice with cecal ligation and puncture.

References:
[1] Trinh M D, Fiserova I, Vacek L, et al. Hypoxia-Induced Sarcoplasmic Reticulum Ca2+ Leak Is Reversed by Ryanodine Receptor Stabilizer JTV-519 in HL-1 Cardiomyocytes[J]. Anatolian Journal of Cardiology, 2022, 26(6): 476.
[2] Yang J, Zhang R, Jiang X, et al. Toll-like receptor 4–induced ryanodine receptor 2 oxidation and sarcoplasmic reticulum Ca2+ leakage promote cardiac contractile dysfunction in sepsis[J]. Journal of Biological Chemistry, 2018, 293(3): 794-807.

Chemical Properties

CAS No.
145903-06-6
Synonyms
K201 free base
SMILES
COC1=CC=C2C(CN(C(CCN3CCC(CC4=CC=CC=C4)CC3)=O)CCS2)=C1
Molecular Formula
C25H32N2O2S
Molecular Weight
424.6
Solubility
Soluble in DMSO
Storage
Store at -20°C
General tips
Select a suitable solvent according to the product solubility data. Once prepared, aliquot the stock solution to avoid repeated freeze-thaw cycles.
Use stock solutions within 6 months when stored at -80°C or within 1 month when stored at -20°C.
To improve solubility, warm the tube to 37°C and sonicate it for an appropriate period.
Shipping Condition
Evaluation samples are shipped with blue ice. Other available sizes are shipped at room temperature or with blue ice upon request.

CalculatorsMolarity / Dilution / Molecular Weight / Unit Conversion / In Vivo Formulation / Solubility

g/mol

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