| 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 |
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| Targets |
IRE1α (IC50 = 0.6 µM)
The primary target of KIRA6 is IRE1α (inositol-requiring enzyme 1 alpha), a key protein involved in the unfolded protein response (UPR). IRE1α is a transmembrane protein with both kinase and RNase domains that is activated during endoplasmic reticulum (ER) stress. KIRA6 is a potent type II IRE1α kinase inhibitor with an IC50 of 0.6 µM. It is an allosteric inhibitor of IRE1α RNase kinase activity. By inhibiting IRE1α, KIRA6 can modulate the UPR and reduce ER stress-induced cell death. |
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| ln Vitro |
KIRA6 inhibits Tg's autophosphorylation of IRE1α and Tm's splicing of XBP1 mRNA in INS-1 cells in a dose-dependent manner[1].
KIRA6 is a potent type II IRE1α kinase inhibitor with an IC50 of 0.6 µM. It can trigger an apoptotic response and has anti-inflammatory and immune-modulating properties. The compound supports cell survival and stops ER stress-induced cell aging in vivo. By inhibiting IRE1α, KIRA6 can reduce ER stress-induced apoptosis and promote cell survival. Its anti-inflammatory properties suggest additional therapeutic applications for inflammatory diseases. |
| ln Vivo |
KIRA6 protects the functional viability of photoreceptors intravitreally in rat models of ER stress-induced retinal degeneration. Systematically, KIRA6 protects pancreatic β-cells in Akita diabetic mice, boosts insulin, and lowers hyperglycemia. In vivo, KIRA6 inhibits IRE1α to maintain cell viability and function in a variety of cells and rodent tissues under ER stress. When administered intraperitoneally (i.p.) to BALB/c mice at a dose of 10 mg/kg, KIRA6 has a good plasma AUC (AUC 0-24h = 14.3 μM*h) and a moderate clearance (22.4 mL/min/kg). The drug has a 3.90-hour half-life, a Cmax of 3.3 μM, and plasma levels at 4 and 8 hours of 1.2 μM and 0.33 μM, respectively[1].
KIRA6 supports cell survival and stops ER stress-induced cell aging in vivo. It was created to block IRE1α-mediated cell death. The compound's ability to inhibit IRE1α and modulate the UPR makes it a valuable tool for studying ER stress and its role in various diseases. Its anti-inflammatory and immune-modulating properties suggest potential applications in inflammatory and autoimmune conditions. However, specific in vivo studies have not been detailed in the available literature. |
| Enzyme Assay |
No specific non-cell assay protocol is available for KIRA6. For IRE1α kinase inhibitors, standard cell-free assays use recombinant IRE1α kinase domain and measure autophosphorylation or phosphorylation of peptide substrates. The compound is incubated with the enzyme and ATP, and kinase activity is measured by radioactive or fluorescent methods. These assays provide quantitative data on the compound's potency (IC50) against IRE1α kinase. Selectivity profiling against a panel of kinases can be performed to assess specificity.
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| Cell Assay |
Drugs were administered to cells at different concentrations.
No specific cell-based assay protocol is available for KIRA6. For IRE1α inhibitors, standard cellular assays involve treatment of cells with ER stress-inducing agents (e.g., tunicamycin, thapsigargin) in the presence or absence of KIRA6. IRE1α activation is measured by XBP1 mRNA splicing (by RT-PCR), IRE1α autophosphorylation (by western blot), or IRE1α RNase activity assays. Apoptosis is assessed by Annexin V/PI staining or caspase activity assays. Cell viability is measured using MTT or CellTiter-Glo assays. |
| Animal Protocol |
BALB/c mice
10 mg/kg i.p. No specific animal protocol is available for KIRA6. For studying ER stress in vivo, standard models include diseases associated with ER stress such as neurodegenerative diseases, metabolic disorders, and inflammatory conditions. KIRA6 is administered (route and dose to be determined) for 2-4 weeks. ER stress markers, cell death, and disease progression are assessed. The compound's effects on cell survival and aging can be evaluated in appropriate models. |
| ADME/Pharmacokinetics |
No detailed pharmacokinetic data is publicly available for KIRA6. The compound has a molecular weight of 518.53 and formula C28H25F3N6O. The chemical name is 3-(4-{8-amino-3-tert-butylimidazo[1,5-a]pyrazin-1-yl}naphthalen-1-yl)-1-[3-(trifluoromethyl)phenyl]urea. It is soluble in DMSO at ≥6 mg/mL. As a small molecule with moderate lipophilicity, it would be expected to have reasonable cell permeability. Comprehensive pharmacokinetic studies would be required for therapeutic development.
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| Toxicity/Toxicokinetics |
No detailed toxicology data is publicly available for KIRA6. As a research compound, standard preclinical toxicology would be required for therapeutic development. The compound's ability to modulate the UPR and ER stress suggests potential for both therapeutic effects and side effects related to UPR modulation. The compound is for research use only and not for therapeutic applications.
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| References | |
| Additional Infomation |
KIRA6 has the molecular formula C28H25F3N6O and molecular weight 518.53. The chemical name is 3-(4-{8-amino-3-tert-butylimidazo[1,5-a]pyrazin-1-yl}naphthalen-1-yl)-1-[3-(trifluoromethyl)phenyl]urea. It is also known as KIRA-6 and IRE1 Inhibitor IV. It is a potent type II IRE1α kinase inhibitor with an IC50 of 0.6 µM and an allosteric inhibitor of IRE1α RNase kinase activity. The compound supports cell survival and stops ER stress-induced cell aging in vivo. No clinical trial status has been identified.
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| Molecular Formula |
C28H25F3N6O
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| Molecular Weight |
518.5329
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| Exact Mass |
518.204
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| Elemental Analysis |
C, 64.86; H, 4.86; F, 10.99; N, 16.21; O, 3.09
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| CAS # |
1589527-65-0
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| Related CAS # |
1589527-65-0
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| PubChem CID |
73425700
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| Appearance |
Solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.645
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| LogP |
6.26
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
38
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| Complexity |
834
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(C1C=CC=C(C=1)NC(NC1=CC=C(C2=CC=CC=C21)C1=C2C(N)=NC=CN2C(C(C)(C)C)=N1)=O)(F)F
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| InChi Key |
NOHQEAFAESMMDX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H25F3N6O/c1-27(2,3)25-36-22(23-24(32)33-13-14-37(23)25)20-11-12-21(19-10-5-4-9-18(19)20)35-26(38)34-17-8-6-7-16(15-17)28(29,30)31/h4-15H,1-3H3,(H2,32,33)(H2,34,35,38)
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| Chemical Name |
1-[4-(8-amino-3-tert-butylimidazo[1,5-a]pyrazin-1-yl)naphthalen-1-yl]-3-[3-(trifluoromethyl)phenyl]urea
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| Synonyms |
KIRA6; KIRA 6; KIRA-6
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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: 25~60 mg/mL (48.2~115.7 mM)
Ethanol: ~60 mg/mL (~115.7 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.5 mg/mL (0.96 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.5 mg/mL (0.96 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 0.5 mg/mL (0.96 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9285 mL | 9.6426 mL | 19.2853 mL | |
| 5 mM | 0.3857 mL | 1.9285 mL | 3.8571 mL | |
| 10 mM | 0.1929 mL | 0.9643 mL | 1.9285 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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