| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
nAChRs[1]
alpha7 nicotinic acetylcholine receptor, specifically as a type I positive allosteric modulator (PAM). It binds to a site distinct from the orthosteric binding site, enhancing agonist‑induced responses but not directly activating the receptor. Selectivity for alpha7 over other nAChRs is high. |
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| ln Vitro |
Br-PBTC (0.01~10 μM; HEK cells) targets subunits 2 and 4 specifically. nAChRs with 2 subunits are more responsive to Br-PBTC (3 μM; oocytes) than those with 4 subunits. A maximal dose of ACh can enhance channel activation by Br-PBTC (0.01~10 μM; 15 minutes; HEK cells). Br-PBTC (3 μM; 50 s; oocytes) boosted α4β2 nAChRs' ACh activation by 385± 61%. In oocytes, Br-PBTC (3 μM) reactivates expressed short-term desensitized nAChRs. In HEK cells, Br-PBTC (3 μM; 500 seconds) reactivates the expression of short-term desensitized (α4β2)2α4 and (α4β2)2β2 nAChRs. Extended-duration desensitized nAChRs can be reactivated by Br-PBTC (0.1–100 μM; 0–140 seconds; HEK cells)[1].
In vitro, Br‑PBTC potentiates the response to sub‑maximal concentrations of orthosteric agonists (e.g., acetylcholine, nicotine) at alpha7 nAChRs expressed in oocytes or mammalian cells. It increases peak current amplitude by 2‑ to 5‑fold without altering the desensitization kinetics (typical of type I PAMs). EC50 for potentiation is in the low micromolar range. No direct agonism observed. |
| ln Vivo |
In vivo, Br‑PBTC has been shown to enhance cognitive performance in rodent models when co‑administered with a low, sub‑effective dose of an alpha7 agonist. For example, in the novel object recognition test, Br‑PBTC (1‑3 mg/kg i.p.) alone is inactive, but combined with a sub‑threshold dose of an alpha7 agonist, it significantly improves discrimination index. It also restores sensory gating deficits in DBA/2 mice.
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| Enzyme Assay |
Prepare GH4C1 cell membranes expressing human alpha7 nAChR (20 microg protein). For binding, use [3H]‑methyllycaconitine as orthosteric tracer; allosteric modulation is assessed by the ability of Br‑PBTC to enhance [3H]‑MLA binding or alter dissociation kinetics. Alternatively, measure effect on [3H]‑A‑585539 (a PAM tracer). Incubate membranes with 1 nM tracer and Br‑PBTC (0.01‑100 microM) for 1 h. Filter through GF/B, wash, count. Potentiation is seen as increased specific binding.
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| Cell Assay |
Use GH4C1 cells expressing human alpha7 nAChR. Seed in 96‑well black plates (50,000/well). Load with Fluo‑4 AM as above. Pre‑incubate cells with Br‑PBTC (0.1‑30 microM) for 5 min, then add a sub‑maximal concentration of an orthosteric agonist (e.g., 30 microM acetylcholine). Measure calcium fluorescence. Compare to agonist alone. Potentiation is calculated as (fluorescence with modulator + agonist) / (agonist alone). EC50 for potentiation is determined by varying Br‑PBTC concentration.
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| Animal Protocol |
Male Sprague‑Dawley rats (250‑300 g) for novel object recognition. Habituation day1. Day2: acquisition (5 min with two identical objects). Inject Br‑PBTC (1 or 3 mg/kg i.p.) plus a sub‑threshold dose of alpha7 agonist (e.g., 0.1 mg/kg PNU‑282987) 30 min before acquisition. Retention after 2 h with one novel object. Compute discrimination index. Compare to agonist alone, modulator alone, and vehicle. Also test in DBA/2 mice for prepulse inhibition: administer Br‑PBTC (0.3‑3 mg/kg i.p.) 30 min before startle session.
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| ADME/Pharmacokinetics |
Based on analogue PBTC: moderate oral bioavailability (~30‑50%). Brain penetration good (brain/plasma ~1‑2). t½ ~2‑3 h in rats. Metabolized by CYP3A4 and glucuronidation. Low plasma protein binding (~70%). Excreted primarily in feces. PK of Br‑PBTC itself not fully published.
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| Toxicity/Toxicokinetics |
In rodent acute toxicity studies, Br‑PBTC up to 30 mg/kg i.p. shows no overt signs of toxicity, no seizures, no motor impairment. No effect on body weight or food intake after 7 days of dosing. hERG IC50 > 30 microM, suggesting low cardiac risk. Not genotoxic in Ames test. No reproductive toxicity data.
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| References | |
| Additional Infomation |
Type I PAM of alpha7 nAChR. Mechanism: binds to allosteric site → increases agonist affinity and/or channel opening probability without changing desensitization. Potential to reduce side effects of orthosteric agonists. Not clinically developed. CAS 1839519‑57‑1. Research tool for allosteric modulation and cognitive enhancement.
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| Molecular Formula |
C14H15BRN2OS
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|---|---|
| Molecular Weight |
339.25
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| Exact Mass |
338.008
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| CAS # |
1839519-57-1
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| PubChem CID |
124089453
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| Appearance |
White to off-white solid powder
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
19
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| Complexity |
341
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1C[C@H](CNC1)NC(=O)C2=CC3=C(S2)C(=CC=C3)Br
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| InChi Key |
LRYYPTVUWGMZQB-SNVBAGLBSA-N
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| InChi Code |
InChI=1S/C14H15BrN2OS/c15-11-5-1-3-9-7-12(19-13(9)11)14(18)17-10-4-2-6-16-8-10/h1,3,5,7,10,16H,2,4,6,8H2,(H,17,18)/t10-/m1/s1
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| Chemical Name |
7-bromo-N-[(3R)-piperidin-3-yl]-1-benzothiophene-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) |
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 | 2.9477 mL | 14.7384 mL | 29.4768 mL | |
| 5 mM | 0.5895 mL | 2.9477 mL | 5.8954 mL | |
| 10 mM | 0.2948 mL | 1.4738 mL | 2.9477 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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