KIRA-7 (KIRA7) is an imidazopyrazine-based anti-fibrotic compound acting as an IRE1α kinase/Rnase inhibitor with the potential to be used in fibrosis. It allosterically inhibits IRE1α kinase with an IC50 of 0.11/0.22 uM. It is able to reverse bleomycin-induced fibrosis when given 2 weeks after bleomycin exposure in vivo.
Physicochemical Properties
| Molecular Formula | C27H23FN6O |
| Molecular Weight | 466.509528398514 |
| Exact Mass | 466.191 |
| CAS # | 1937235-76-1 |
| PubChem CID | 121596794 |
| Appearance | White to off-white solid powder |
| LogP | 5.1 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 35 |
| Complexity | 779 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | FC1=CC=CC(=C1)NC(NC1=CC=C(C2C=CC=CC=21)C1=C2C(N)=NC=CN2C(C2(C)CC2)=N1)=O |
| InChi Key | BMEJPYIGRYVVEF-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C27H23FN6O/c1-27(11-12-27)25-33-22(23-24(29)30-13-14-34(23)25)20-9-10-21(19-8-3-2-7-18(19)20)32-26(35)31-17-6-4-5-16(28)15-17/h2-10,13-15H,11-12H2,1H3,(H2,29,30)(H2,31,32,35) |
| Chemical Name | 1-[4-[8-amino-3-(1-methylcyclopropyl)imidazo[1,5-a]pyrazin-1-yl]naphthalen-1-yl]-3-(3-fluorophenyl)urea |
| Synonyms | KIRA7 KIRA 7 |
| 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 |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | The alveolar epithelial cell line MLE12 can have its XBP1 splicing inhibited by KIRA-7 [1]. |
| ln Vivo | Spliced XBP1 and ATF4 were lower in C57BL6 mice treated with KIRA-7 (5 mg/kg; i.p.; once daily for 14 days) than in mice treated with vehicle or subjected to bleomycin. Similarly, bleomycin exposure led to a considerable increase in the mRNA levels of BiP and CHOP, while KIRA-7 treatment of bleomycin-exposed animals decreased these levels. Collagen 1A1 and fibronectin mRNA levels were markedly decreased following KIRA-7 therapy [1]. |
| Animal Protocol |
Animal/Disease Models: C57BL6 mice (12 weeks old) Bleomycin (1.5 units/kg) [1] Doses: 5 mg/kg Route of Administration: intraperitoneal (ip) injection; daily; continued for 14 days Experimental Results: Result in splicing of XBP1 and ATF4 reduction. Likewise, the mRNA levels of BiP and CHOP were also Dramatically diminished. |
| References |
[1]. Small molecule inhibition of IRE1α kinase/RNase has anti-fibrotic effects in the lung. PLoS One. 2019 Jan 9;14(1):e0209824. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~214.36 mM) |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1436 mL | 10.7179 mL | 21.4358 mL | |
| 5 mM | 0.4287 mL | 2.1436 mL | 4.2872 mL | |
| 10 mM | 0.2144 mL | 1.0718 mL | 2.1436 mL |