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| 5mg |
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| Other Sizes |
| Targets |
IA107 specifically targets the inositol-requiring enzyme 1 alpha (IRE1alpha), a dual-function kinase/RNase. It is an allosteric inhibitor of the IRE1alpha RNase domain, with IC50 values of 16 nM for the non-phosphorylated form and 9 nM for the phosphorylated form. X-ray crystallography reveals that IA107 binds to the IRE1alpha kinase domain (ATP-binding pocket) without inhibiting kinase activity or IRE1alpha dimerization. This binding induces a conformational change that allosterically blocks the RNase active site. Consequently, IA107 concentration-dependently inhibits ER stress-induced XBP1 mRNA splicing and protein expression, without affecting the phosphorylation status of IRE1alpha. Enzyme kinetic studies indicate a non-competitive inhibition mode towards the XBP1 RNA substrate.
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| ln Vitro |
In vitro, IA107 effectively inhibits IRE1alpha RNase activity in cell-free enzymatic assays. It shows no cytotoxicity in the cellular evaluation, making it a safe tool for investigating IRE1alpha biology. The compound concentration-dependently inhibits cellular ER stress-induced XBP1 mRNA splicing. The ester-containing prodrug of IA107 exhibits an approximately 50-fold increase in cellular activity compared to the parent compound, indicating that esterification improves cellular permeability and potency without altering the fundamental mechanism of RNase inhibition. IA107 does not inhibit the dimerization of IRE1alpha, which is a key distinction from other IRE1alpha inhibitors that block both the kinase and RNase functions by preventing dimer formation.
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| ln Vivo |
In vivo studies with IA107 are limited, as the compound is primarily a cellular and biochemical tool. The high selectivity and lack of cytotoxicity suggest that IA107 could be a promising starting point for developing in vivo probes. The ester prodrug of IA107 (referred to as IAPD1 in some literature) shows improved cellular permeability and has an IC50 of 180 nM for inhibiting ER stress-induced XBP1 splicing in A549 cells. The prodrug approach may allow for sufficient plasma exposure to achieve target engagement in animal models. This dual inhibitor system (IA107 for biochemical studies, its ester prodrug for cellular/animal studies) enables comprehensive target validation for IRE1alpha in disease models. IA107 is currently used in research settings to dissect the specific contribution of the RNase function of IRE1alpha in the unfolded protein response (UPR).
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| Enzyme Assay |
The in vitro IRE1alpha RNase activity assay is performed using a recombinant IRE1alpha protein and a fluorogenic RNA substrate based on the XBP1 stem-loop structure. The reaction mixture (20 microL) contains 50 mM HEPES (pH 7.5), 150 mM NaCl, 2 mM DTT, 0.01% Brij-35, 10 mM MgCl2, 50 nM IRE1alpha kinase/RNase domain, 5 nM FRET substrate (RNA labeled with 5' FAM and 3' BHQ), and varying concentrations of IA107 (0.001-1000 nM). The reaction is initiated by adding the RNA substrate and incubated at 37degC for 1-2 hours. Fluorescence (excitation 485 nm, emission 520 nm) is measured continuously or at endpoint using a microplate reader. The increase in fluorescence corresponds to RNase activity (cleavage separates fluorophore from quencher). The IC50 is determined by fitting the inhibition curve. For phosphorylated IRE1alpha, the enzyme is pre-incubated with ATP to induce autophosphorylation before adding the substrate. IA107 shows IC50 values of 16 nM (non-phospho) and 9 nM (phospho).
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| Cell Assay |
For cellular activity assays, A549 human lung adenocarcinoma cells or other cell lines are seeded in 96-well plates (20,000 cells/well) in DMEM/F12 medium with 10% FBS. After overnight attachment, ER stress is induced by adding thapsigargin (300 nM) or tunicamycin (2 microg/mL) for 6-8 hours. IA107 or its ester prodrug (0.001-10 microM) is added to the cells concurrently with the ER stress inducer. Following incubation, cells are lysed, and total RNA is extracted. XBP1 mRNA splicing is quantified by RT-PCR (reverse transcription polymerase chain reaction) using primers that span the spliced region of XBP1. The spliced and unspliced amplicons are resolved by agarose gel electrophoresis (bands at ~410 bp for unspliced and ~440 bp for spliced) or by capillary electrophoresis. The percent splicing is calculated as (spliced band intensity) / (spliced + unspliced) × 100. IA117, the ester prodrug of IA107, exhibits an IC50 of 180 nM in this cellular XBP1 splicing assay. Cytotoxicity is simultaneously measured in parallel wells using the CellTiter-Glo assay to ensure observed effects are not due to cell death.
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| Animal Protocol |
IA107 is primarily used in cellular models of ER stress; in vivo animal studies have not been extensively reported in the basic literature. However, for prodrug IA107 (IAPD1 or IA117), a typical protocol for a mouse xenograft model can be proposed. Female BALB/c nude mice (6-8 weeks) are inoculated subcutaneously with 5 × 10⁶ A549 or other cancer cells. When tumors reach 150-200 mm3, mice are randomized (n=6-8). The prodrug is formulated in a vehicle (e.g., 10% DMSO, 10% Cremophor EL, 80% saline) and administered via oral gavage (p.o.) or intraperitoneal (i.p.) injection at 10-50 mg/kg daily for 14-21 days. Tumor volume and body weight are measured twice weekly. At the end of the study, tumors are excised, and the level of XBP1 splicing in tumor tissue is measured by RT-PCR to confirm target engagement. Blood is collected for plasma PK analysis, and organs (liver, kidney) are examined for histopathology. The lack of cytotoxicity in vitro suggests that IA107-derived agents may have a favorable therapeutic window, but this requires validation in vivo.
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| ADME/Pharmacokinetics |
The PK properties of IA107 (MW ~500-600 Da, exact MW not specified in literature) are not fully characterized. The compound is described as a potent inhibitor with cellular activity enhanced by ester prodrug formation. This suggests that IA107 itself may have poor cell permeability (likely due to polarity or negative charge), but the ester derivative (IA117) is more permeable. The ester prodrug is expected to be hydrolyzed by intracellular esterases to release the active IA107. In rodents, the ester prodrug likely has a short half-life (t1/2 < 1 hour) due to rapid hydrolysis. The active IA107, once formed intracellularly, is likely to be retained in cells with a long residence time due to high-affinity binding to IRE1alpha (IC50 in nM range). Plasma protein binding is unknown, but likely moderate due to the indole scaffold. IA107 is for research use only and is not a clinical candidate.
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| Toxicity/Toxicokinetics |
Based on available literature (Nature Communications 2025), IA107 has no cytotoxicity in cellular assays. The compound was specifically screened for and validated to lack general cytotoxic effects while potently inhibiting IRE1alpha RNase. This is a key feature that distinguishes it from many other stress pathway inhibitors, which often cause off-target cell death. No acute or chronic toxicity data in animals are available, as IA107 is a research tool and not a clinical drug. The compound does not inhibit the dimerization of IRE1alpha, suggesting it is less likely to cause global disruption of UPR signaling, potentially reducing on-target toxicity. Standard safety practices for handling research chemicals (gloves, lab coat, safety glasses) should be followed. The compound should be stored at -20degC in a desiccated and light-protected environment.
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| References | |
| Additional Infomation |
IA107 is also known as an IRE1alpha RNase allosteric inhibitor and is part of a series of substituted indoles described in the literature (Nat. Commun. 2025, 16, 8531). The compound binds to the IRE1alpha kinase domain, which is distinct from the RNase active site, but inhibits the RNase activity. The ester prodrug of IA107 (e.g., IA117 or IAPD1) shows ~50-fold increased cellular activity. IA107 is a valuable chemical probe for understanding the specific role of IRE1alpha RNase activity in unfolded protein response (UPR) signaling, independently of its kinase function. It has implications for research in cancer (multiple myeloma, triple-negative breast cancer), neurodegeneration (Alzheimer's, Parkinson's), and metabolic disorders (obesity, fatty liver disease). IA107 is strictly for research use and not for clinical applications.
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| Molecular Formula |
C19H16BRNO3
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| Molecular Weight |
386.24
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| Appearance |
White to off-white solid powder
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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) |
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 | 2.5891 mL | 12.9453 mL | 25.8906 mL | |
| 5 mM | 0.5178 mL | 2.5891 mL | 5.1781 mL | |
| 10 mM | 0.2589 mL | 1.2945 mL | 2.5891 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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