JTV-519 free base (Synonyms: K201 free base) |
Catalog No.GC36371
One-Click Copy Product Info
|
JTV-519 free base is a Ca2+-dependent blocker of SERCA that inhibits the ATPase activity.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 145903-06-6
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
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.
| 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: | |
| Cas No. | 145903-06-6 | SDF | |
| Synonyms | K201 free base | ||
| Canonical SMILES | COC1=CC=C2C(CN(C(CCN3CCC(CC4=CC=CC=C4)CC3)=O)CCS2)=C1 | ||
| Formula | C25H32N2O2S | M.Wt | 424.6 |
| Solubility | Soluble in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.3552 mL | 11.7758 mL | 23.5516 mL |
| 5 mM | 471 μL | 2.3552 mL | 4.7103 mL |
| 10 mM | 235.5 μL | 1.1776 mL | 2.3552 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 29 reference(s) in Google Scholar.)