| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg | |||
| Other Sizes |
| Targets |
RO2959 HCl targets the calcium release-activated calcium (CRAC) channel, which is composed of Orai1 and STIM1 proteins. The CRAC channel mediates store-operated calcium entry (SOCE) in immune cells, which is essential for T cell activation, cytokine production, and proliferation. By inhibiting the CRAC channel, RO2959 HCl blocks calcium influx, thereby suppressing T cell activation and immune responses.
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| ln Vitro |
RO2959 has an IC50 of 25 nM for Orai1 and 530 nM for Orai3 inhibition. With an IC50 value of 265 nM, RO2959 inhibits store-operated calcium entry (SOCE) in activated CD4+ T cells [1]. Strong SOCE inhibitor RO2959 inhibits IP3-dependent currents in human primary CD4+ T cells stimulated by T cell receptor (TCR)-triggered SOCE stimulation or thapsigargin therapy, as well as in CRAC-expressing RBL-2H3 cells and CHO cells that stably express human Orai1 and Stim1. TCR-stimulated or MLR (mixed lymphocyte reaction)-mediated T cell proliferation is fully inhibited by RO2959 [1].
In vitro, RO2959 HCl is a potent inhibitor of the CRAC channel with an IC50 of 0.38 µM. It inhibits calcium influx in T cells, leading to reduced cytokine production and T cell proliferation. Its activity is confirmed in calcium flux assays using immune cells or cell lines expressing Orai1 and STIM1. It shows selectivity for the CRAC channel over other ion channels. |
| ln Vivo |
In vivo, RO2959 HCl has been used to study the role of CRAC channels in immune responses and autoimmune diseases. Its ability to inhibit T cell activation suggests potential applications in autoimmune and inflammatory conditions. However, specific in vivo efficacy data are limited.
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| Enzyme Assay |
Cell-free assays for RO2959 HCl are not standard because it targets an ion channel. Its ability to inhibit CRAC channel-mediated calcium influx can be assessed using calcium flux assays in cells expressing Orai1 and STIM1. Its binding to Orai1 or STIM1 can be studied using surface plasmon resonance or co-immunoprecipitation.
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| Cell Assay |
Cellular assays for RO2959 HCl are performed using immune cells, such as T cells or Jurkat cells. Cells are loaded with a calcium-sensitive fluorescent dye and treated with varying concentrations of RO2959 HCl. Calcium influx is induced by thapsigargin or other store-depleting agents, and the inhibition of calcium flux is measured. Cytokine production is measured by ELISA.
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| Animal Protocol |
In vivo animal experiments for RO2959 HCl are not extensively documented. To study its effects on immune responses, animal models of autoimmune diseases could be used. Animals would be administered RO2959 HCl, and disease severity, immune cell activation, and cytokine production would be assessed.
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| ADME/Pharmacokinetics |
RO2959 HCl has a molecular weight of approximately 450 g/mol and a molecular formula that is proprietary. It is a solid powder with a purity of >98%. It is soluble in DMSO and should be stored under recommended conditions. Its pharmacokinetic properties are not well characterized.
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| Toxicity/Toxicokinetics |
The toxicological profile of RO2959 HCl has not been extensively characterized. As a CRAC channel inhibitor, it may have immunosuppressive effects. No significant toxicity has been reported. Comprehensive toxicology studies are lacking. It is a research compound and is not approved for clinical use.
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| References | |
| Additional Infomation |
RO2959 HCl is a potent and selective CRAC channel inhibitor used as a research compound to study calcium signaling in immune cells. It inhibits the Orai1/STIM1-mediated calcium influx with an IC50 of 0.38 µM. It has potential applications in autoimmune and inflammatory research. It is not approved for clinical use.
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| Molecular Formula |
C21H20CLF2N5OS
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|---|---|
| Molecular Weight |
463.931208610535
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| Exact Mass |
463.104
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| CAS # |
1219927-22-6
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| Related CAS # |
RO2959 monohydrochloride;2309172-44-7
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| PubChem CID |
45274292
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
31
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| Complexity |
655
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(CN(CC1)C2=NC=C(S2)C)C3=CN=C(C=N3)NC(=O)C4=C(C=CC=C4F)F.Cl
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| InChi Key |
GMLSDODALBRLPE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H19F2N5OS.ClH/c1-12-6-7-28(21-26-8-13(2)30-21)11-14(12)17-9-25-18(10-24-17)27-20(29)19-15(22)4-3-5-16(19)23/h3-5,8-10H,6-7,11H2,1-2H3,(H,25,27,29)1H
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| Chemical Name |
2,6-Difluoro-N-{5-[4-methyl-1-(5-methyl-thiazol-2-yl)-1,2,5,6-tetrahydro-pyridin-3-yl]-pyrazin-2-yl}-benzamide Hydrochloride
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| Synonyms |
RO2959 RO 2959RO2959 Hydrochloride RO2959 HCl RO-2959
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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 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)
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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 | 2.1555 mL | 10.7775 mL | 21.5550 mL | |
| 5 mM | 0.4311 mL | 2.1555 mL | 4.3110 mL | |
| 10 mM | 0.2155 mL | 1.0777 mL | 2.1555 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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