| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
IRE1α kinase-IN-1 targets IRE1α (inositol-requiring enzyme 1α), a transmembrane kinase and endoribonuclease that is a key sensor of the unfolded protein response (UPR) in the endoplasmic reticulum. Upon ER stress, IRE1α oligomerizes and autophosphorylates, activating its RNase domain to splice XBP1 mRNA, which leads to the production of the transcription factor XBP1s. By inhibiting IRE1α kinase activity (IC₅₀ of 77 nM), the compound prevents IRE1α oligomerization, autophosphorylation, and RNase activity (IC₅₀ of 80 nM).
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| ln Vitro |
In human cells, IRE1α kinase-IN-1 (Compound 31) suppresses endoribonuclease activity and stops IRE1α oligomerization and phosphorylation caused by endoplasmic reticulum stress [1]. With only 4 out of 455 kinases showing >70% inhibition, IRE1α kinase-IN-1 is incredibly selective. With an IC50 of 160 nM, IRE1α kinase-IN-1 prevents autophosphorylation of the recombinant G547 IRE1α KEN domain pS274. With an IC50 of 0.74 μM, IRE1α kinase-IN-1 suppresses tunicamycin-induced GFP-IRE1α foci in HEK293 cells. With an IC50 of 0.27 μM, IRE1α kinase-IN-1 prevents ATP site LanthaScreen tracer from binding to recombinant dephosphorylated G547 IRE1α KEN [1]. With an IC50 range of 0.68-1.63 μM, IRE1α kinase-IN-1 suppresses XBP1 luciferase fusion mRNA splicing in HEK293 cells that is stimulated by thapsigargin and tunicamycin [1]. In NCI-H929 cells, IRE1α kinase-IN-1 (0 – 20 μM) dose-dependently suppresses tunicamycin-induced XBP1 expression. IRE1α kinase-IN-1 (0 – 20 μM) reduces IRE1α-dependent XBP1s mRNA expression in H929 cells. inside cells [1].
In vitro, IRE1α kinase-IN-1 demonstrates potent and selective inhibition of IRE1α with an IC₅₀ of 77 nM. The compound inhibits ER stress-induced IRE1α oligomerization and autophosphorylation, as well as IRE1α RNase activity with an IC₅₀ of 80 nM. It shows high selectivity, inhibiting only 4 out of 455 kinases by more than 70%. The compound dose-dependently inhibits tunicamycin-induced expression of XBP1s in NCI-H929 cells. |
| ln Vivo |
In vivo activity data for IRE1α kinase-IN-1 are limited. As a potent and selective IRE1α inhibitor, the compound is expected to demonstrate efficacy in animal models of diseases where the UPR plays a pathogenic role, such as cancer, neurodegeneration, and metabolic disorders. Typical in vivo studies involve administration to disease models, with assessment of IRE1α signaling and disease-related endpoints.
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| Enzyme Assay |
For non-cellular in vitro enzyme assays, IRE1α kinase-IN-1 is evaluated for its inhibitory activity against purified IRE1α kinase and RNase domains. The compound is incubated with IRE1α, ATP, and a substrate, and kinase activity is measured. RNase activity is assessed using an XBP1 splicing assay or a fluorogenic substrate. IC₅₀ values of 77 nM for kinase inhibition and 80 nM for RNase inhibition are determined.
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| Cell Assay |
For in vitro cellular assays, IRE1α kinase-IN-1 is tested in cells such as NCI-H929 to assess its effects on IRE1α signaling. Cells are treated with serial dilutions of the compound in the presence of ER stress inducers (such as tunicamycin). XBP1 splicing is measured by RT-PCR or Western blot. IRE1α phosphorylation and oligomerization are assessed by immunoprecipitation and Western blot.
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| Animal Protocol |
For in vivo animal studies, IRE1α kinase-IN-1 would typically be evaluated in mouse models of diseases associated with ER stress and the UPR. Mice are treated with the compound via oral or intraperitoneal administration. IRE1α signaling biomarkers (XBP1 splicing, IRE1α phosphorylation) are assessed in target tissues. Disease-related endpoints such as tumor growth, neurodegeneration, or metabolic parameters are measured.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for IRE1α kinase-IN-1 are limited. As a small-molecule kinase inhibitor with a molecular weight of 504.99, it is expected to have moderate oral bioavailability and tissue distribution. The compound is soluble in DMSO and can be formulated for in vivo administration. Further pharmacokinetic studies would be needed to fully characterize its absorption, distribution, metabolism, and excretion profile.
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| Toxicity/Toxicokinetics |
Toxicological data for IRE1α kinase-IN-1 are limited. As a highly selective IRE1α inhibitor, the compound may have on-target effects on normal cellular functions regulated by the UPR. Comprehensive toxicology studies including acute and repeat-dose toxicity, genotoxicity, and organ-specific toxicity assessments would be required for therapeutic development. The compound is for research use only and not for human use.
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| References | |
| Additional Infomation |
IRE1α kinase-IN-1 is a selective inhibitor of IRE1α with an IC₅₀ of 77 nM for kinase inhibition and 80 nM for RNase inhibition. It is 100-fold more selective for IRE1α than IRE1β and inhibits only 4 out of 455 kinases by more than 70%. The compound has a molecular formula of C₂₆H₂₆ClFN₈ and a molecular weight of 504.99. It is a valuable tool for studying the unfolded protein response and IRE1α signaling.
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| Molecular Formula |
C26H26CLFN8
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| Molecular Weight |
504.99
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| Exact Mass |
504.195
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| CAS # |
2328097-41-0
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| PubChem CID |
139593294
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| Appearance |
White to off-white solid powder
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| LogP |
5.3
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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 |
6
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| Heavy Atom Count |
36
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| Complexity |
720
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1C(=CC2=C(C=1)NC(NC1C=CC=CC=1)=N2)C1=CN=C2C(NCC3CCN(C)CC3)=CC(=NN12)Cl
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| InChi Key |
BPRAHARGXSNSSO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H26ClFN8/c1-35-9-7-16(8-10-35)14-29-22-13-24(27)34-36-23(15-30-25(22)36)18-11-20-21(12-19(18)28)33-26(32-20)31-17-5-3-2-4-6-17/h2-6,11-13,15-16,29H,7-10,14H2,1H3,(H2,31,32,33)
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| Chemical Name |
3-(2-anilino-6-fluoro-1H-benzimidazol-5-yl)-6-chloro-N-[(1-methylpiperidin-4-yl)methyl]imidazo[1,2-b]pyridazin-8-amine
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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 mg/mL (49.51 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.95 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 25.0 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: ≥ 2.5 mg/mL (4.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9802 mL | 9.9012 mL | 19.8024 mL | |
| 5 mM | 0.3960 mL | 1.9802 mL | 3.9605 mL | |
| 10 mM | 0.1980 mL | 0.9901 mL | 1.9802 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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