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Chemical Structure| 249537-73-3 Chemical Structure| 249537-73-3

Structure of NFAT Inhibitor-1
CAS No.: 249537-73-3

Chemical Structure| 249537-73-3

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The NFAT Inhibitor (VIVIT peptide) is a cell-permeable peptide that selectively inhibits the calcineurin-mediated dephosphorylation of nuclear factor of activated T cells (NFAT).

Synonyms: VIVIT peptide; NFAT Inhibitor

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Product Details of NFAT Inhibitor-1

CAS No. :249537-73-3
Formula : C75H120N20O22S
M.W : 1685.94
SMILES Code : O=C([C@H]1N(CCC1)C(CNC([C@H](C)NC([C@@H](N)CCSC)=O)=O)=O)N[C@@H](CC2=CNC=N2)C(N(CC)[C@@H](C)C(N[C@@H](C(C)C)C(N[C@]([C@@H](C)CC)([H])C(N[C@@H](C(C)C)C(N[C@]([C@@H](C)CC)([H])C(N[C@]([C@H](O)C)([H])C(NCC(N3[C@@H](CCC3)C(N[C@H](C(N[C@@H](CCC(O)=O)C(N[C@H](C(O)=O)CCC(O)=O)=O)=O)CC4=CNC=N4)=O)=O)=O)=O)=O)=O)=O)=O)=O
Synonyms :
VIVIT peptide; NFAT Inhibitor
MDL No. :MFCD02683959
InChI Key :QPMHUXBSHGAVGD-MCDIZDEASA-N
Pubchem ID :16135717

Safety of NFAT Inhibitor-1

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Bone marrow-derived macrophages (BMMs) 5 µM 1 hour Inhibited LPS-induced expression of TNF, MIP-1α and IL-1β Cell Signal. 2011 Nov;23(11):1785-93.
Primary murine microglia 10 µM 24 hours To assess the effect of NFAT inhibitors on cytokine and neurotoxin secretion by Aβ-stimulated microglia. Results showed that tat-VIVIT and FK506 significantly attenuated Aβ- and LPS-stimulated secretion of TNFα and IL-6. J Neuroinflammation. 2015 Mar 4;12:42.
LN229 cells 500 µM 24 hours and 48 hours To evaluate the effect of Sim2-VIVIT on NFAT signaling, results showed Sim2-VIVIT did not affect the pattern of NFATc1 bands or NFAT-dependent promoter activity Molecules. 2021 Aug 7;26(16):4785.
U87 cells 20 µM 25 hours To evaluate the effect of 11R-VIVIT on NFAT activity, results showed 11R-VIVIT at 20 µM upregulated NFAT-dependent promoter activity, but the increase was not statistically significant Molecules. 2021 Aug 7;26(16):4785.
LN229 cells 20 µM 25 hours To evaluate the effect of 11R-VIVIT on NFAT activity, results showed 11R-VIVIT at 10 µM and 20 µM activated NFAT-dependent promoter activity Molecules. 2021 Aug 7;26(16):4785.
ARPE-19 cells 10 µM 4 hours pretreatment followed by 24 hours LPS treatment To evaluate the effect of VIVIT on LPS-induced NFAT luciferase activity, results showed that VIVIT significantly reduced LPS-induced luciferase activity. Int J Mol Sci. 2021 Aug 12;22(16):8684.
Bone marrow macrophages 1 µM 48 hours Inhibited NFATc1 expression and significantly downregulated Nod1 mRNA expression PLoS Pathog. 2013 Jan;9(1):e1003152.
HPV E6/E7 immortalized mouse RPE cells 20 µM 48 hours To study the effect of VIVIT on starvation-induced TFEB nuclear localization, results showed that VIVIT caused TFEB retention in the cytoplasm. Int J Mol Sci. 2021 Aug 12;22(16):8684.
ARPE-19 cells 20 µM 48 hours To investigate the effect of NFAT inhibition on TFEB expression, results showed that VIVIT treatment did not significantly alter TFEB expression levels. Int J Mol Sci. 2021 Aug 12;22(16):8684.
Mouse bone marrow macrophages (BMMs) 2.0 µM 96 hours To investigate the effect of VIVIT peptide on wear particle-induced osteoclastogenesis from BMMs. Results showed that VIVIT significantly inhibited wear particle (Ti and PMMA)-induced osteoclast formation and bone resorption activity. Acta Pharmacol Sin. 2013 Nov;34(11):1457-66.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
APP/PS1 transgenic mice Alzheimer's disease model Subcutaneous injection 0.5 mg/kg/day Continuous for 28 days To evaluate the effect of NFAT inhibitors on microglial activation, Aβ plaque load, and memory in APP/PS1 mice. Results showed that FK506 and tat-VIVIT significantly attenuated microgliosis and Aβ plaque load but did not significantly affect memory performance. J Neuroinflammation. 2015 Mar 4;12:42.
Mice Renal retrograde infection model Intraperitoneal injection 10 mg/kg Once daily for 48 hours 11R-VIVIT significantly impaired neutrophil bacterial phagocytic killing capacity and increased renal susceptibility to UPEC PLoS Pathog. 2013 Jan;9(1):e1003152.
Mice Aortic banding (AB)-induced cardiac hypertrophy model Subcutaneous injection 10 mg/kg Every 2 days for 4 weeks Inhibition of NFAT activity, alleviating the aggravated cardiac hypertrophy pathology caused by Nulp1 deficiency J Am Heart Assoc. 2020 Aug 18;9(16):e016419
Mice Aortic banding (AB)-induced cardiac hypertrophy model Subcutaneous osmotic pump 10 mg/kg/day Once daily for 2 weeks Pre-treatment with VIVIT significantly attenuated AB-induced cardiac remodeling abnormalities in IRF8/C0//C0 mice, as evidenced by reduced ratios of HW/BW, LW/BW and HW/TL, and decreased cardiomyocyte cross-sectional area and collagen volume. Nat Commun. 2014;5:3303
Rat Regenerating and adult rat muscles Intramuscular injection 50 μg 7 days The VIVIT peptide blocked Cn-mediated NFAT activation, inhibited the expression of slow myosin heavy chain (MyHC-slow), and upregulated the expression of fast myosin heavy chains (MyHC-2X and MyHC-2B). Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10590-5

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

0.59mL

0.12mL

0.06mL

2.97mL

0.59mL

0.30mL

5.94mL

1.19mL

0.59mL

Dissolving Methods
The prepared working fluid is recommended to be prepared now and used up as soon as possible in a short period of time. The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1

References

 

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