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| Targets |
CRAC (Ca2+ release-activated Ca2+) channels (Orai family) [1]
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| ln Vitro |
Compound 5J-4 potently blocked store-operated Ca2+ entry (SOCE) in HeLa-OSN cells (stable expressing Orai1, STIM1 and NFAT-GFP) with efficacy comparable to that observed with compound 5D. [1]
Compound 5J-4 also blocked endogenous SOCE in primary murine TH17 cells, showing a blocking effect comparable to compound 5D. [1] |
| ln Vivo |
5J-4 decreases the expression of RORα and RORγt and the generation of IL-17 [1]. The intraperitoneal administration of 5J-4 (2 mg/kg) every other day for 30 days alleviates symptoms and postpones the start of EAE [1].
In a mouse model of experimental autoimmune encephalomyelitis (EAE), intraperitoneal injection of 5J-4 at 2 mg/kg every other day starting from day 0 after disease induction with MOG35-55/CFA dramatically reduced the clinical symptoms and delayed the onset of EAE, demonstrating protective effects on autoimmunity. [1] Consistent with the reduced clinical score, the number of infiltrated mononuclear cells into the central nervous system (CNS) was reduced, and in particular the infiltrated CD4+ population was significantly decreased in 5J-4-treated mice. [1] Analysis of mononuclear cells isolated from draining lymph nodes and CNS of 5J-4-treated animals showed a predominant reduction in IL-17A+ population, while that of IFN-γ+ cells was not significantly reduced. [1] Approximately 70% of 5J-4-treated mice exhibited this phenotype; about 30% of animals showed strong resistance to EAE with reduction in both IFN-γ+ and IL-17A+ populations. [1] mRNA levels of RORα and RORγt were dramatically reduced in draining lymph nodes of 5J-4-injected mice, while those of T-bet and Foxp3 were not significantly affected. [1] |
| Cell Assay |
To measure block of SOCE by 5J-4 in HeLa-OSN cells or primary TH17 cells, cells were loaded with Fura-2 AM for 30-45 min, attached onto coverslips, and perfused with Ca2+-free Ringer's solution. Ca2+ stores were passively depleted with thapsigargin, and store-operated Ca2+ entry was measured by exchanging the Ca2+-free Ringer's solution with that containing 2 mM CaCl2. At the peak of SOCE, cells were exposed to the same solution containing 5J-4, and the Fura-2 emission ratio (340/380) was acquired. [1]
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| Animal Protocol |
Animal/Disease Models: C57BL/6 mice (MOG35-55 peptide immunized mice) [1]
Doses: 2 m/kg Route of Administration: intraperitoneal (ip) injection, every other day, for 30 days Experimental Results: Dramatically diminished symptoms and delayed EAE attacks and reduce the incidence of EAE. The number of monocytes infiltrating into the central nervous system and Dramatically reducing the number of infiltrating CD4+ cell populations. For EAE induction in C57BL/6 mice, animals were immunized subcutaneously on day 0 with 100 μg of MOG35-55 peptide emulsified in complete Freund's adjuvant (CFA) supplemented with 5 mg/mL of Mycobacterium tuberculosis H37Ra. Mice were also injected intraperitoneally with 200 ng/mouse of pertussis toxin on day 0 and 2. 5J-4 was administered intraperitoneally at a dose of 2 mg/kg every other day starting from day 0 after disease induction. Control mice received DMSO vehicle. Clinical scores were recorded according to a standard scoring system (0: no clinical signs; 1: limp tail; 2: partial hind leg paralysis; 3: complete hind leg paralysis or partial hind and front leg paralysis; 4: complete hind and partial front leg paralysis). [1] |
| Toxicity/Toxicokinetics |
In vivo injection of 5J-4 at 2 mg/kg every other day did not cause any lethality in mice, in contrast to compound 5D which caused mortality at the same dose regimen. [1]
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| References | |
| Additional Infomation |
5J-4 is a structural analogue of compound 5D, identified by removing the trichloride (-Cl3) motif that was responsible for in vivo toxicity of compound 5D. [1]
5J-4 is a CRAC channel blocker that can be considered as a chemical template for development of therapeutic agents to suppress inflammatory responses, particularly TH17-mediated autoimmunity. [1] |
| Molecular Formula |
C16N2O3SH12
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|---|---|
| Molecular Weight |
312.3431
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| Exact Mass |
312.056
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| CAS # |
827001-82-1
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| PubChem CID |
2968289
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| Appearance |
White to off-white solid powder
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| LogP |
3.8
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
22
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| Complexity |
432
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC1C=C2C(=CC=1)C(NC(=S)NC(C1OC=CC=1)=O)=CC=C2
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| InChi Key |
WMUSJLJASFXGHN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H12N2O3S/c19-11-6-7-12-10(9-11)3-1-4-13(12)17-16(22)18-15(20)14-5-2-8-21-14/h1-9,19H,(H2,17,18,20,22)
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| Chemical Name |
N-((6-hydroxynaphthalen-1-yl)carbamothioyl)furan-2-carboxamide
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| Synonyms |
5J 4 5J4 5J-4
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2016 mL | 16.0082 mL | 32.0164 mL | |
| 5 mM | 0.6403 mL | 3.2016 mL | 6.4033 mL | |
| 10 mM | 0.3202 mL | 1.6008 mL | 3.2016 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.
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