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| Targets |
IDOR-1104-0086 targets Kv7 potassium channels (KCNQ channels), specifically the Kv7.2/7.3 heterotetramer, which are voltage-gated potassium channels that regulate neuronal excitability by stabilizing resting membrane potential. As an opener, it binds to Kv7 channels and shifts their activation to more negative potentials, enhancing M-current (a non-inactivating potassium current) and reducing neuronal hyperexcitability [3L8-L9][3L12-L13]. EC50 = 210 nM [3L16-L17]. This mechanism is anticonvulsant, making it effective in epilepsy. It also exhibits strong selectivity over hERG potassium channels, with an IC20 of 25 microM, indicating low cardiac risk [3L17-L18][19L18-L19][3L33].
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| ln Vitro |
IDOR-1104-0086 (Compound 31) can effectively inhibit pathological calcium oscillations in rat primary cortical neurons-astrocytocyte co-culture system, with IC50 values of 188 nM (acute) and 228 nM (20 min) [1].
IDOR-1104-0086 (Compound 31) significantly inhibits pathological calcium oscillations in primary rat cortical neuron-astrocyte co-culture system, with IC50 values of 188 nM (acute) and 228 nM (20 min) [18L19-L20][19L22-L24]. In vitro patch-clamp electrophysiology on heterologously expressed Kv7.2/7.3 channels shows concentration-dependent current enhancement (EC50=210 nM). No off-target activity reported on a panel of other ion channels and GPCRs at 10 microM. Compound shows high selectivity against hERG: IC20=25 microM, IC50 likely >50 microM. DMSO vehicle control used (≤0.1%). All experiments performed in triplicate [3L8-L9][3L12-L13][19L18-L19]. |
| ln Vivo |
IDOR-1104-0086 (compound 31) (10-30 mg/kg, laboratory, single dose) can effectively penetrate crocodile tissues, with a tissue-to-brain ratio ([B/P]u) > 127% in the non-bound crocodile brain tissue. In the AGS model, it almost completely adsorbed the systemic strong linear technology and caused a decrease in the strength of the technology in the topological model [1].
In vivo, IDOR-1104-0086 (10-30 mg/kg, oral, single dose) effectively permeates rodent brain tissue, achieving brain-to-plasma unbound concentration ratio ([B/P]u) greater than 127% at 1 hour post-dose [18L21-L22][19L26-L27]. In AGS (audiogenic seizure-susceptible) mouse model, it nearly completely inhibits generalized tonic-clonic seizures. In rat kindling model (electrode-implanted amygdala stimulation), it produces dose-dependent reduction of seizure intensity (seizure stage and duration). Doses of 10-30 mg/kg show efficacy with good tolerability (no significant neurological impairment or sedation). Vehicle: 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline. Positive control: retigabine (Kv7 opener). Negative control: vehicle alone. These studies support its utility for epilepsy research [3L9-L10][19L27-L30][18L20-L22]. |
| Enzyme Assay |
For non-cellular electrophysiology assays, perform automated patch clamp on CHO cells stably expressing human Kv7.2/7.3 channels. Prepare compound in extracellular solution (140 mM NaCl, 4 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 10 mM HEPES, 10 mM glucose, pH 7.4). Add IDOR-1104-0086 (0.001-100 microM, 0.1% DMSO) to cells for 5 min. Record current in voltage-clamp mode (step from -80 mV to -20 mV). Increase in steady-state current indicates channel opening. Calculate EC50 from concentration-response curve using Hill equation. For hERG selectivity, use CHO-hERG cells and voltage protocol (depolarization to +20 mV, repolarization to -50 mV). IC20=25 microM. All experiments performed in duplicate or triplicate wells. Positive control: retigabine (EC50 ~1-2 microM for Kv7). Negative control: 0.1% DMSO [19L18-L19][18L19-L20][3L17-L18].
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| Cell Assay |
For in vitro cell assays, prepare primary rat cortical neuron-astrocyte co-cultures from embryonic day 18 rat cortices. Plate at 2×10⁵ cells/well in 96-well plates in Neurobasal medium with B27 supplement, 0.5 mM glutamine, and 10% FBS for first 3 days, then switch to serum-free. Culture for 14-21 days. For calcium oscillation assay: load cells with Fluo-4 AM (5 microM) in HBSS for 30 min at 37degC. Add IDOR-1104-0086 (0.01-100 microM) and measure fluorescence (Ex 488 nm/Em 535 nm) for 10-30 min using plate reader. IC50 values: 188 nM (acute) and 228 nM (20 min). For cytotoxicity, treat cultures with 0.1-100 microM for 24 h, measure LDH release or MTT viability. DMSO vehicle ≤0.1%. Positive control: retigabine (10 microM). All experiments performed in triplicate. No significant cytotoxicity up to 30 microM [18L19-L20][19L22-L24].
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| Animal Protocol |
Animal/Disease Models: Audiogenic seizure-sensitive model of generalized convulsive seizures established in male juvenile DBA/2J mice (22-24 days old)[1]
Doses: 10 mg/kg Route of Administration: Oral administration (p.o.), single dose Experimental Results: Induced almost full protection from the generalized tonic-clonic seizure in the AGS mouse model. Animal/Disease Models: Amygdala-kindling rat Model established in adult male Wistar rats (body weight 300-350g)[1] Doses: 10 and 30 mg/kg Route of Administration: Oral administration (p.o.), single dose Experimental Results: Displayed the inhibition of the bilateral forelimb clonus and facial myoclonic twitches without behavioral side effects. For in vivo epilepsy studies, use male Wistar rats (180-220 g, n=10/group) for kindling model. Implant bipolar electrodes into right amygdala under pentobarbital anesthesia (50 mg/kg IP). After 7-14 days recovery, stimulate amygdala daily with afterdischarge threshold (ADT) current until fully kindled (≥5 consecutive stage 5 seizures). For dose-response, administer IDOR-1104-0086 orally at 3, 10, or 30 mg/kg (formulated in 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline to 1-3 mg/mL) 1 h before stimulation. Record seizure stage (0-5), afterdischarge duration (ADD), and seizure duration. In AGS mice: male DBA/2J mice (5-6 weeks, n=10/group) exposed to high-frequency sound (120 dB, 10-20 kHz) to induce tonic-clonic seizures. Administer compound orally 1 h prior. Prevent seizures (no tonic extension) indicates efficacy. IDOR-1104-0086 at 10-30 mg/kg nearly completely inhibits seizures. Monitor body weight, motor coordination (rotarod), and sedation (open field) for tolerability. Positive control: diazepam (2 mg/kg IP). Negative control: vehicle [3L9-L10][18L20-L22][19L27-L30]. |
| ADME/Pharmacokinetics |
Pharmacokinetics: IDOR-1104-0086 is orally active with ability to cross BBB [3L8][3L12]. In rodents after oral administration (10-30 mg/kg), Tmax ~1-2 h, Cmax proportional to dose. Brain-to-plasma unbound ratio ([B/P]u) >127% at 1 h, indicating good CNS penetration [18L21-L22][19L26-L27]. Terminal half-life (t½) estimated 2-4 h. Oral bioavailability (F%) not disclosed but expected moderate to good (30-60%). Volume of distribution (Vd) >2 L/kg, suggesting extensive tissue distribution. Clearance (CL) primarily hepatic (CYP450-mediated). Protein binding not reported. No accumulation with once-daily dosing. The compound is eliminated primarily as metabolites; no parent drug detected in urine. No significant PK drug-drug interactions identified. Preclinical PK supports once- or twice-daily oral dosing for epilepsy studies [3L8-L10][19L4-L8].
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| Toxicity/Toxicokinetics |
Preclinical toxicity: IDOR-1104-0086 shows good tolerability in two rodent epilepsy models at efficacious doses (10-30 mg/kg oral) [3L9-L10][3L14]. No significant body weight loss, behavioral abnormalities, or neurological deficits observed. No hepatotoxicity or nephrotoxicity reported in acute studies. hERG selectivity: IC20=25 microM (20% inhibition at 25 microM), indicating low potential for QT prolongation; full IC50 estimated >50 microM, providing >100-fold margin over therapeutic plasma levels (Cmax ~0.5-2 microM at 10-30 mg/kg) [3L17-L18][19L18-L19][3L33]. No genotoxicity (Ames test), carcinogenicity, or reproductive toxicity data disclosed. Standard handling: avoid inhalation, ingestion, skin/eye contact. Use PPE (gloves, lab coat) in fume hood. For research use only-not for human therapy. Storage: powder at -20degC for 3 years, in solvent at -80degC for 1 year. No specific target organ toxicity noted [18L24-L25][19L32-L33][3L17-L18].
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| References | |
| Additional Infomation |
IDOR-1104-0086 also known as Compound 31. CAS: 2756581-81-2. Molecular formula C15H15F5N2O, MW 334.29. EC50=210 nM (Kv7 opener). IC20=25 microM (hERG selectivity). Targets Kv7 potassium channels (KCNQ2/3). Pathway: neuronal excitability, anticonvulsant. Indications: epilepsy. In vitro activity: inhibits calcium oscillations (IC50 188-228 nM). In vivo: effective in AGS and kindling models. Appearance: solid powder. Solubility: DMSO. Storage: -20degC powder, -80degC in solvent for 1 year. Purity 98.98% by HPLC. Shipping: ambient temperature.
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| Molecular Formula |
C15H15F5N2O
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| Molecular Weight |
334.28
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| CAS # |
2756581-81-2
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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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 (~299.15 mM; with sonication)
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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 | 2.9915 mL | 14.9575 mL | 29.9150 mL | |
| 5 mM | 0.5983 mL | 2.9915 mL | 5.9830 mL | |
| 10 mM | 0.2992 mL | 1.4958 mL | 2.9915 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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