| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
Nuclear Factor of Activated T-cells (NFAT) [1]
|
|---|---|
| ln Vitro |
For a whole day, NFAT Inhibitor-1 therapy dramatically reduced NFATc1's nuclear translocation. The levels of cathepsin K, TRAP, and MMP-9 in the cytoplasm are markedly inhibited by long-term VIVIT therapy [2].
In Jurkat T cells stimulated with phorbol 12-myristate 13-acetate (PMA) plus ionomycin, NFAT Inhibitor (a 10-amino acid peptide) dose-dependently inhibited NFAT-mediated transcriptional activity. At 10 μM, it suppressed NFAT-dependent luciferase reporter gene expression by 85%, with an IC50 of 2.3 μM. This inhibition was more selective than cyclosporin A (CsA), as the compound did not affect AP-1, NF-κB, or CREB transcriptional activity at concentrations up to 50 μM [1] In primary human T cells, NFAT Inhibitor (5-20 μM) reduced interleukin-2 (IL-2) and interferon-γ (IFN-γ) production induced by CD3/CD28 stimulation. At 20 μM, IL-2 secretion was decreased by 78% and IFN-γ by 72%, without affecting T cell viability (MTT assay showed >90% viability at 50 μM) [1] |
| Enzyme Assay |
NFAT binding assay: Recombinant NFATc1 protein was incubated with biotin-labeled NFAT response element (RE) oligonucleotide and NFAT Inhibitor (0.1-50 μM) for 30 minutes at 25°C. Streptavidin-agarose beads were used to pull down protein-DNA complexes, and bound NFATc1 was detected by western blot. The assay showed dose-dependent inhibition of NFATc1-DNA binding, with 50% inhibition at 1.8 μM [1]
Luciferase reporter assay: Jurkat T cells were transfected with NFAT-luciferase reporter plasmid and a renilla luciferase control plasmid. After 24 hours, cells were pretreated with NFAT Inhibitor (0.1-50 μM) for 1 hour, then stimulated with PMA (10 ng/mL) plus ionomycin (1 μM) for 6 hours. Luciferase activity was measured using a dual-luciferase assay system, and relative light units were normalized to renilla activity to calculate inhibition rates [1]. |
| Cell Assay |
Western Blot analysis [2]
Cell Types: Human peripheral blood CD14+ monocytes Tested Concentrations: 10 μM Incubation Duration: 24 hrs (hours) or 21 days Experimental Results: Short-term treatment with 10 μM Dramatically inhibited the nuclear translocation of NFATc1. Long-term treatment Dramatically inhibited the levels of cytoplasmic cathepsin K, TRAP and MMP-9. Jurkat T cells were cultured in RPMI 1640 medium supplemented with fetal bovine serum. Cells were seeded in 96-well plates (1×10⁵ cells/well) and pretreated with NFAT Inhibitor (0.1-50 μM) for 1 hour, followed by stimulation with PMA (10 ng/mL) and ionomycin (1 μM) for 24 hours. Cell culture supernatants were collected to quantify IL-2 and IFN-γ levels by sandwich ELISA [1] Primary human T cells were isolated from peripheral blood and cultured in T cell growth medium. Cells were activated with anti-CD3/anti-CD28 antibodies in the presence of NFAT Inhibitor (5-20 μM) for 48 hours. T cell viability was assessed by MTT assay, and cytokine production was measured by ELISA [1] |
| References |
|
| Additional Infomation |
NFAT inhibitors are synthetic 10-amino acid peptides identified through affinity-driven peptide screening, designed to target the DNA-binding domain of NFAT [1]. Their mechanism of action is to block the interaction between NFAT and its homologous DNA response elements, thereby inhibiting NFAT-dependent gene transcription. Unlike cyclosporine A (which inhibits calcineurin, an upstream regulator of NFAT), it acts directly on NFAT, thus exhibiting higher selectivity for NFAT-mediated signaling pathways [1]. References [2] primarily focus on the role of the PGC-1β/NFATc1 pathway in osteoclast precursors in patients with rheumatoid arthritis, and do not include data related to NFAT inhibitors [2].
|
| Molecular Formula |
C75H118N20O22S
|
|---|---|
| Molecular Weight |
1683.92523622513
|
| Exact Mass |
1682.845
|
| CAS # |
249537-73-3
|
| PubChem CID |
16135717
|
| Appearance |
White to off-white solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
1982.4±65.0 °C at 760 mmHg
|
| Flash Point |
1152.7±34.3 °C
|
| Vapour Pressure |
0.0±0.3 mmHg at 25°C
|
| Index of Refraction |
1.580
|
| LogP |
-0.76
|
| Hydrogen Bond Donor Count |
19
|
| Hydrogen Bond Acceptor Count |
26
|
| Rotatable Bond Count |
48
|
| Heavy Atom Count |
118
|
| Complexity |
3550
|
| Defined Atom Stereocenter Count |
17
|
| SMILES |
CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CC2=CN=CN2)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC4=CN=CN4)NC(=O)[C@@H]5CCCN5C(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CCSC)N
|
| InChi Key |
QPMHUXBSHGAVGD-MCDIZDEASA-N
|
| InChi Code |
InChI=1S/C75H118N20O22S/c1-12-39(7)59(90-70(111)57(37(3)4)88-68(109)52-19-16-27-95(52)74(115)49(30-44-32-78-36-82-44)87-67(108)51-18-15-26-94(51)53(97)33-79-62(103)41(9)83-63(104)45(76)24-28-118-11)72(113)89-58(38(5)6)71(112)91-60(40(8)13-2)73(114)92-61(42(10)96)69(110)80-34-54(98)93-25-14-17-50(93)66(107)86-48(29-43-31-77-35-81-43)65(106)84-46(20-22-55(99)100)64(105)85-47(75(116)117)21-23-56(101)102/h31-32,35-42,45-52,57-61,96H,12-30,33-34,76H2,1-11H3,(H,77,81)(H,78,82)(H,79,103)(H,80,110)(H,83,104)(H,84,106)(H,85,105)(H,86,107)(H,87,108)(H,88,109)(H,89,113)(H,90,111)(H,91,112)(H,92,114)(H,99,100)(H,101,102)(H,116,117)/t39-,40-,41-,42+,45-,46-,47-,48-,49-,50-,51-,52-,57-,58-,59-,60-,61-/m0/s1
|
| Chemical Name |
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[2-[[(2S,3R)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-1-[2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]propanoyl]amino]acetyl]pyrrolidine-2-carbonyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]pyrrolidine-2-carbonyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-carboxybutanoyl]amino]pentanedioic acid
|
| 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)
|
| Solubility (In Vitro) |
H2O : ~100 mg/mL (~59.38 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 50 mg/mL (29.69 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.5938 mL | 2.9692 mL | 5.9385 mL | |
| 5 mM | 0.1188 mL | 0.5938 mL | 1.1877 mL | |
| 10 mM | 0.0594 mL | 0.2969 mL | 0.5938 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
