| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
alpha7 nicotinic acetylcholine receptor (alpha7 nAChR). Ki values: 0.2‑0.6 nM for rat and human cortical alpha7 nAChRs. >100‑fold selective over alpha4beta2 and alpha3beta4 subtypes. Minimal off‑target binding to a broad panel of receptors, ion channels, and enzymes.
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| ln Vitro |
Full agonist at alpha7 nAChRs, leading to Ca2+ influx and activation of ERK1/2 and CREB. In progranulin‑deficient cells, ABT‑107 suppresses NF‑kappaB activation and reduces TNFalpha levels. Also reduces tau hyperphosphorylation in cell models. EC50 for functional activation (calcium flux) is in the low nanomolar range.
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| ln Vivo |
In rodents with a brain/plasma ratio of 1, ABT-107 demonstrates strong CNS penetration and good bioavailability in mice (orally, 51.1%; intraperitoneally, 100%), rats (orally, 81.2%; intraperitoneally, 100%), and monkeys (orally, 40.6%; intramuscularly, 100%)[1]. ABT-107 (0.01-1 μmol/kg ip, 15 min prior to sacrifice) increases CREB and ERK1/2 in a dose-dependent manner[1]. In mouse cortex and hippocampus, ABT-107 (0.01, 0.1, and 1.0 mg/kg ip) raises S9-GSK3 and lowers p-tau[1]. In AD transgenic APP-tau mice, ABT-107 (5 mg/kg/day ip) infusion reduces tau hyperphosphorylation[1].
In 6‑OHDA rat model of Parkinson's disease, ABT‑107 protects nigrostriatal neurons. In progranulin‑deficient mice, it reduces microgliosis, TNFalpha, and compulsive behavior. Enhances sensory gating in DBA/2 mice (blocked by alpha7 antagonist). At 1‑3 micromol/kg i.p., increases ACh release in rat hippocampus. Reduces p‑tau in mouse cortex/hippocampus. |
| Enzyme Assay |
Prepare rat cortical or human alpha7‑expressing HEK membranes (15‑20 microg protein). Incubate with 0.5‑2 nM [3H]‑methyllycaconitine or [¹2⁵I]‑alpha‑Bungarotoxin and 0.01 nM‑10 microM ABT‑107 in 50 mM Tris‑HCl pH 7.4 with 120 mM NaCl, 5 mM KCl, 1 mM MgCl2, 2 mM CaCl2 for 60‑120 min at RT. Non‑specific: 10 microM alpha‑Bungarotoxin or 100 microM nicotine. Filter through GF/B (0.3% PEI), wash, count. Ki = 0.2‑0.6 nM.
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| Cell Assay |
Use GH4C1 cells stably expressing human alpha7 nAChR. Seed 50,000/well in 96‑well black plates in F‑10/15% horse serum/2.5% FBS for 48 h. Load with 2.5 microM Fluo‑4 AM in HBSS/HEPES/probenecid for 60 min at 37degC. Wash, add ABT‑107 (0.1 nM‑10 microM). Measure fluorescence (ex/em 485/525 nm) for calcium influx. Alternatively, whole‑cell patch‑clamp recording to measure agonist‑induced inward currents. EC50 is determined from concentration‑response curve.
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| Animal Protocol |
Animal/Disease Models: Rats (male Sprague-Dawley; 350-380 g b.wt.)[1].
Doses: 1, 3 μmol/kg. Route of Administration: IP daily for 3 days. Experimental Results: Induced a significant, dose-dependent increase in ACh release by day 3 of repeated administration. Higher doses may be required to evoke ACh release in naive rats not engaged in stimulated, ie, cognitive-related behavior. Animal/Disease Models: Female TAPP (and wild-type littermates) mice[1]. Doses: 1 mg/kg. Route of Administration: Continuous subcutaneous (sc) infusion for 2 weeks. Experimental Results: Produced a dose-dependent increase in Ser9 phosphorylation in the cingulate cortex 15 min after acute administration in mice. Male DBA/2 mice (20‑30 g). Anesthetize with urethane (1.5 g/kg i.p.). Implant recording electrode into hippocampus (AP −2.0 mm, ML 1.5 mm, DV 1.2 mm). Administer ABT‑107 i.p. (0.1 or 1.0 micromol/kg) 30‑180 min before recording. Deliver paired auditory clicks (500 ms interval) and record hippocampal P20‑N40 evoked potentials. Calculate gating ratio (test/conditioning). For ACh release, use rat microdialysis after daily ABT‑107 (1‑3 micromol/kg i.p.) for 3 days. |
| ADME/Pharmacokinetics |
Oral bioavailability: 51% (mouse), 81% (rat), 41% (monkey). i.p. and i.m. bioavail 100%. Brain‑to‑plasma ratio ≥1. t½ in humans 7‑10 h (Phase I). Metabolized via N‑oxidation (FMO1, M1) and indole oxidation (CYP3A4/1A2/2J2/2D6, M2). M1 primary in rat, M2 in monkey/human. Nonlinear PK in humans.
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| Toxicity/Toxicokinetics |
Well tolerated at therapeutic doses (1‑3 micromol/kg). No significant off‑target binding to 70 other receptors. In two‑week infusion (1 mg/kg s.c.) in transgenic mice, no overt toxicity. Not approved for clinical use. No carcinogenicity or reproductive toxicity data publicly available. Standard lab safety precautions.
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| References |
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| Additional Infomation |
Highly selective alpha7 full agonist with neuroprotective and procognitive effects. Mechanism: alpha7 activation → Ca2+ influx → ERK/CREB → reduced NF‑kappaB and tau hyperphosphorylation. Phase I clinical trials (safety, PK) completed but no further development. Not FDA‑approved. Used as research tool for neurodegeneration and neuroinflammation. CAS 855291‑54‑2. Research use only.
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| Molecular Formula |
C19H20N4O
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|---|---|
| Molecular Weight |
320.39
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| Exact Mass |
320.163
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| CAS # |
855291-54-2
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| PubChem CID |
11151363
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
598.0±50.0 °C at 760 mmHg
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| Flash Point |
315.4±30.1 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.699
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| LogP |
2.18
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
24
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| Complexity |
439
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1CN2CCC1[C@H](C2)OC3=NN=C(C=C3)C4=CC5=C(C=C4)NC=C5
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| InChi Key |
LUKNJAQKVPBDSC-SFHVURJKSA-N
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| InChi Code |
InChI=1S/C19H20N4O/c1-2-16-15(5-8-20-16)11-14(1)17-3-4-19(22-21-17)24-18-12-23-9-6-13(18)7-10-23/h1-5,8,11,13,18,20H,6-7,9-10,12H2/t18-/m0/s1
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| Chemical Name |
5-[6-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxy]pyridazin-3-yl]-1H-indole
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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: 100 mg/mL (312.12 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.80 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 (7.80 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 25.0 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: ≥ 2.5 mg/mL (7.80 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 | 3.1212 mL | 15.6060 mL | 31.2120 mL | |
| 5 mM | 0.6242 mL | 3.1212 mL | 6.2424 mL | |
| 10 mM | 0.3121 mL | 1.5606 mL | 3.1212 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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