| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Target: CRAC (Ca2+ release-activated Ca2+) channels, specifically Orai1 (pore-forming subunit) and STIM1 (endoplasmic reticulum Ca2+ sensor). piCRAC-1 is a photoisomerizable analog of GSK-5498A. In the trans configuration (dark/415 nm), the compound blocks CRAC channels by binding to the Orai1 pore or interfering with STIM1-Orai1 coupling. Under 365 nm light, the compound switches to cis configuration, which is less active or inactive, allowing reversible inhibition.
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| ln Vitro |
In vitro, piCRAC-1 (trans configuration) inhibits CRAC channel-mediated Ca2+ entry in cells expressing Orai1 and STIM1. In electrophysiological patch-clamp recordings, piCRAC-1 blocks ICRAC (calcium release-activated calcium current) with IC50 in the low micromolar range (∼1-5 uM). The cis configuration has significantly reduced inhibitory activity, enabling light-controlled reversible inhibition. No cell viability effects are reported at active concentrations.
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| ln Vivo |
In vivo, piCRAC-1 alleviates thrombocytopenia (low platelet count) and hemorrhage in preclinical models. By inhibiting CRAC channels, it reduces calcium influx in platelets, which is required for platelet activation, aggregation, and clot formation. The photoisomerizable property allows spatially restricted inhibition, potentially reducing systemic bleeding risks. Detailed in vivo efficacy data have been published in preclinical studies.
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| Enzyme Assay |
For cell-free binding assays: not applicable, as CRAC channels are multi-subunit membrane proteins that require assembly of STIM1 and Orai1 for function. For CRAC channel inhibition assays, electrophysiological techniques are used: whole-cell patch-clamp recordings are performed on HEK293 cells co-expressing STIM1 and Orai1 or on RBL-2H3 (rat basophilic leukemia) cells that endogenously express CRAC channels. piCRAC-1 (0.1-100 uM) is applied in the dark (trans configuration) or under 365 nm light (cis configuration). Current inhibition is measured by voltage steps or ramp protocols.
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| Cell Assay |
For cell-based Ca2+ entry assays: HEK293 cells stably expressing STIM1 and Orai1 are seeded on 96-well plates. Cells are loaded with a calcium-sensitive fluorescent dye (Fluo-4 AM, 2-5 uM, 30-60 min at 37degC). Passive Ca2+ store depletion is induced by thapsigargin (1 uM) in Ca2+-free buffer. After depletion, extracellular Ca2+ is added (2 mM), and the resulting Ca2+ influx through CRAC channels is measured by fluorescence plate reader. piCRAC-1 is added prior to Ca2+ readdition, and experiments are performed in the dark or under 365 nm light to assess trans vs. cis activity.
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| Animal Protocol |
For in vivo animal studies: in a mouse model of thrombocytopenia (e.g., induced by anti-platelet antibodies or chemotherapy), piCRAC-1 is administered intravenously or by local injection. Tail bleeding time, whole blood platelet counts, and hemorrhage volume are measured. In a laser-induced thrombosis model in mice, piCRAC-1 is applied locally with light control (365 nm vs. dark) to assess localized inhibition of platelet activation and thrombus formation. Efficacy in alleviating thrombocytopenia and hemorrhage is assessed by monitoring bleeding time and hematocrit levels.
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| ADME/Pharmacokinetics |
PK properties of piCRAC-1: The compound is a monoazo CRAC channel inhibitor (MW 384.28, formula C17H10F6N4). As a photoswitchable compound, its PK is likely similar to the parent GSK-5498A. Predicted PK in rodents after IV administration: short plasma half-life (∼1-2 h), moderate volume of distribution, clearance primarily via hepatic metabolism. Oral bioavailability is likely low. The compound is formulated in DMSO-based vehicles for in vivo administration. Photostability under physiological light conditions must be considered.
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| Toxicity/Toxicokinetics |
No toxicity data have been reported for piCRAC-1. CRAC channel inhibitors in general may cause immunosuppression (since CRAC channels are essential for T cell activation), cardiac arrhythmias (due to roles in cardiac pacemaking), and skeletal muscle dysfunction. The photoinducible nature of piCRAC-1 allows spatially restricted inhibition, potentially reducing systemic toxicities. No acute toxicity studies have been published. The compound is for research use only and not for human administration.
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| References | |
| Additional Infomation |
PiCRAC-1 is a monoazo compound and a photoisomerization analog of GSK-5498A. It is a calcium ion release-activated calcium (CRAC) channel inhibitor, existing in the trans configuration in the dark (415 nm light irradiation) and in the cis configuration under 365 nm light irradiation. It is a calcium channel blocker. PiCRAC-1 belongs to the difluorobenzenes, pyrazoles, trifluoromethylbenzenes, and monoazo compounds.
piCRAC-1 is a research compound not yet approved for clinical use. It is a valuable chemical tool for studying CRAC channel biology with spatiotemporal precision. It has potential applications in light-controlled platelet inhibition for preventing thrombosis while preserving hemostasis, and for studying Ca2+ signaling in immune cells, neurons, and other excitable cells. It may also serve as a lead for developing light-controlled therapies for bleeding disorders and thrombotic diseases. |
| Molecular Formula |
C17H10F6N4
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|---|---|
| Molecular Weight |
384.28
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| Exact Mass |
384.08
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| CAS # |
2418049-54-2
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| PubChem CID |
155930756
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
5.1
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
27
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| Complexity |
506
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1(CC2=C(C(F)(F)F)C=CC=C2F)C=CC(/N=N/C2=C(F)C=CC=C2F)=N1
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| InChi Key |
TXWNZTPRPAPHSE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H10F6N4/c18-12-4-1-3-11(17(21,22)23)10(12)9-27-8-7-15(26-27)24-25-16-13(19)5-2-6-14(16)20/h1-8H,9H2
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| Chemical Name |
(2,6-difluorophenyl)-[1-[[2-fluoro-6-(trifluoromethyl)phenyl]methyl]pyrazol-3-yl]diazene
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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) |
DMSO : ≥ 100 mg/mL (~260.23 mM)
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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 | 2.6023 mL | 13.0113 mL | 26.0227 mL | |
| 5 mM | 0.5205 mL | 2.6023 mL | 5.2045 mL | |
| 10 mM | 0.2602 mL | 1.3011 mL | 2.6023 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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