| 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 = 1.4 nM for human alpha7. >1000‑fold selective over alpha4beta2, alpha3beta4, and muscle nAChRs. No significant off‑target activity at 5‑HT3 receptors or other common CNS targets.
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| ln Vitro |
Bradanicline exhibits a notable preference for the central nervous system over the peripheral nervous system, as evidenced by the more than a thousand-fold gap in affinities between the α7 and α4β2 receptor subtypes and the lack of any discernible effects on muscular or ganglionic nicotinic receptor subtypes[1].
Full agonist at human alpha7 nAChR with EC50 = 17 nM (calcium flux or patch‑clamp in GH4C1 cells). No activity at alpha4beta2, alpha3beta4, or muscle nAChRs up to 10 microM. Used as an activator in BARNI systems, providing robust neuronal inhibition not achievable with partial agonists. |
| ln Vivo |
In animal models of positive and negative symptoms as well as cognitive impairment associated with schizophrenia, bradanicline (0.1–1 mg/kg) demonstrates efficacy[2].
In rodent cognition models (0.1‑1 mg/kg i.p. or p.o.), Bradanicline improves novel object recognition and prepulse inhibition deficits. PET imaging confirms brain penetration and target engagement. However, Phase II trials failed to show efficacy for cognitive symptoms in schizophrenia or ADHD, leading to discontinuation. |
| Enzyme Assay |
Prepare membranes from HEK‑293 cells stably expressing human alpha7 nAChR (10‑20 microg protein). Incubate with 0.5‑2 nM [¹2⁵I]‑alpha‑Bungarotoxin and 0.01 nM‑10 microM Bradanicline in 50 mM Tris‑HCl pH 7.4 with 0.1% BSA for 2‑3 h at RT. Non‑specific: 10 microM unlabeled alpha‑Bungarotoxin. Filter through PEI‑soaked GF/B, wash, count gamma. Ki = 1.4 nM from Cheng‑Prusoff.
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| Cell Assay |
Seed GH4C1 cells expressing human alpha7 nAChR in 96‑well black plates (50,000/well) in F‑10/15% horse serum/2.5% FBS for 48 h. Load with Fluo‑8 or Cal‑520 AM (2.5 microM) in HBSS/HEPES/probenecid for 60 min at 37degC. Add Bradanicline (0.1 nM‑100 microM) and measure fluorescence increase (ex/em 485/525 nm). Fit concentration‑response to four‑parameter logistic to obtain EC50 (~17 nM).
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| Animal Protocol |
Adult male Sprague‑Dawley rats (250‑300 g). Novel object recognition: day1 habituation; day2 acquisition (two identical objects, 5 min) with scopolamine (0.5 mg/kg i.p.) to induce deficit. Administer Bradanicline (0.1‑1.0 mg/kg p.o. or i.p.) 30‑60 min before acquisition. After 2 h, retention trial with one novel object. Calculate discrimination index = (time novel − time familiar)/total exploration. Increase vs. scopolamine control indicates procognitive effect.
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| ADME/Pharmacokinetics |
Oral bioavailability ~50‑80% in rodents. Brain‑to‑plasma ratio >1. t½ in rats ~2‑4 h p.o. Cmax in 1‑2 h. Metabolized by CYP3A4 (liver). Linear PK at 0.1‑10 mg/kg. Crosses BBB readily. Excreted in urine and feces.
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| Toxicity/Toxicokinetics |
Well tolerated up to 30 mg/kg in rodents. At therapeutic doses (0.1‑1 mg/kg) no organ toxicity. At >10 mg/kg, mild GI disturbances and reduced locomotor activity. No mutagenicity (Ames negative), no hERG prolongation at clinical concentrations. Long‑term human toxicity data lacking due to discontinued development.
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| References |
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| Additional Infomation |
Bradanekline is a novel small molecule that modulates the activity of neuronal nicotinic receptor (NNR) subtype α7 (α7). Bradanekline belongs to a new class of drugs used to treat central nervous system diseases and disorders.
Drug Indications It has been studied for the treatment of neurological diseases. Mechanism of Action Bradanekline is a novel small molecule that modulates the activity of neuronal nicotinic receptor (NNR) subtype α7 (α7). α7 NNR is involved in a variety of biological functions. In particular, animal studies have shown that α7 NNR is an important regulator of inflammation caused by injury or infection, as well as cognitive function. α7 NNR plays a role in protecting neurons from degeneration and death, a process known as neuroprotection. Potent alpha7 agonist (EC50=17 nM, Ki=1.4 nM). Mechanism: orthosteric binding → Ca2+ influx → downstream signaling (ERK, CREB). Reached Phase II for cognitive impairment in schizophrenia (NCT01488929) and adult ADHD (NCT01003379). Discontinued in 2013 due to lack of efficacy. Not FDA‑approved. Used as research tool and chemogenetic actuator. CAS 639489‑84‑2. |
| Molecular Formula |
C22H23N3O2
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|---|---|
| Molecular Weight |
361.44
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| Exact Mass |
361.179
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| CAS # |
639489-84-2
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| PubChem CID |
25147644
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| Appearance |
White to off-white solid powder
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| LogP |
3.775
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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 |
4
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| Heavy Atom Count |
27
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| Complexity |
534
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1CN2CCC1[C@H]([C@@H]2CC3=CN=CC=C3)NC(=O)C4=CC5=CC=CC=C5O4
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| InChi Key |
OXKRFEWMSWPKKV-GHTZIAJQSA-N
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| InChi Code |
InChI=1S/C22H23N3O2/c26-22(20-13-17-5-1-2-6-19(17)27-20)24-21-16-7-10-25(11-8-16)18(21)12-15-4-3-9-23-14-15/h1-6,9,13-14,16,18,21H,7-8,10-12H2,(H,24,26)/t18-,21+/m0/s1
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| Chemical Name |
N-[(2S,3R)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide
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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 (69.17 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.92 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 (6.92 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 (6.92 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 | 2.7667 mL | 13.8336 mL | 27.6671 mL | |
| 5 mM | 0.5533 mL | 2.7667 mL | 5.5334 mL | |
| 10 mM | 0.2767 mL | 1.3834 mL | 2.7667 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.
Link: https://clinicaltrials.gov/ct2/show/NCT03622216
Conditions:Chronic CoughLink: https://clinicaltrials.gov/ct2/show/NCT01488929
Conditions:Schizophrenia|Negative Symptoms|Cognitive DysfunctionLink: https://clinicaltrials.gov/ct2/show/NCT01003379
Conditions:Cognitive Dysfunction|Schizophrenia
Title:Efficacy, Safety, and Tolerability of TC-5619 in Adults With Attention Deficit/Hyperactivity Disorder (ADHD)
Status:Completed
updateDate:2013-09-13
Ctid:NCT01124708
Link: https://clinicaltrials.gov/ct2/show/NCT01124708
Conditions:ADHDLink: https://clinicaltrials.gov/ct2/show/NCT01254448
Conditions:Alzheimer's DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT01472991
Conditions:Attention Deficit Hyperactivity DisorderProducts are for research use only; We do not sell to patients
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