| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg | |||
| 100mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
BL-1249 targets K2P2.1 (TREK-1) and K2P10.1 (TREK-2) potassium channels. It acts as a selective activator of the TREK subfamily of K2P channels, showing approximately 10-fold greater activity against K2P2.1 and K2P10.1 compared to K2P4.1 (TRAAK). The compound interacts with the negatively charged activator site on K2P channels and modulates channel opening. It also inhibits cyclooxygenase (COX) enzyme.
|
|---|---|
| ln Vitro |
In human bladder myocytes that have been cultured, BL-1249 causes a concentration-dependent membrane hyperpolarization. This can be measured using direct electrophysiological measurement (EC50 = 1.49 μM) or the voltage-sensitive dye bis(1,2-dibutylbarbituric acid)trimethanine oxocyanine (EC50 of 1.26 μM). With an EC50 of 21.0 μM, BL-1249 causes concentration-dependent hyperpolarization in human aortic smooth muscle cells [1]. When evaluated at the maximum dose (10 μM), BL-1249 did not cause concentration-dependent relaxation of 30 mM KCl-induced contractions in rat bladder strips, but it did in rat aorta strips. These results were obtained from in vitro organ bath tests. Impact. ). Ba2+ at concentrations of 1 and 10 mM partially inhibits the bladder relaxation that BL-1249 produces. A selective agonist belonging to the TREK subfamily is BL-1249. Its effect on K2P2.1 (TREK-1) and K2P10.1 (TREK-2) when applied extracellularly is preferential over K2P4.1 (TRAAK), and its mechanism of action is found to be dependent on the gating of the selective filter C-type gate [2].
In vitro, BL-1249 demonstrates concentration-dependent membrane depolarization in cultured human bladder myocytes as assessed by voltage-sensitive dye fluorescence reduction (EC50 = 1.26 ± 0.6 μM) or direct electrophysiological measurement (EC50 = 1.49 ± 0.08 μM). Patch-clamp experiments show that BL-1249 stimulates the selectivity filter 'C-type' gate that controls K2P function. Studies on mutants and K2P2.1/K2P4.1 chimeras highlight the critical role of the C-terminal tail in BL-1249 action and identify the M2/M3 transmembrane helix interface as a key site for selectivity. |
| ln Vivo |
In vivo, isovolumetric bladder contractions are inhibited by BL-1249 (1 mg/kg). The brief half-life of BL-1249's effect on bladder contraction (30 minutes) could potentially be attributed to the compound's quick clearance following intravenous treatment (0.69 hours) [1]. The study found that BL-1249 (1 mg/kg) had minimal impact on mean arterial pressure. This finding aligns with the in vitro bladder's selectivity for vasorelaxants [1].
In vivo, BL-1249 (1 mg/kg intravenous) reduces the number of isovolumic contractions in anesthetized rat models without significantly affecting blood pressure. This demonstrates that BL-1249 exhibits bladder versus vascular selectivity as a potassium channel activator in both in vitro and in vivo settings. The compound has also been used as an activator of mechano-gated K2P channels in contracted mouse ileum and colon tissues. |
| Enzyme Assay |
Not specifically documented for BL-1249. For potassium channel activators, typical cell-free binding assays involve radioligand displacement or fluorescence-based membrane potential measurements using isolated membrane preparations. BL-1249's activity is primarily characterized through electrophysiological techniques rather than direct binding assays. The compound is known to interact with the negatively charged activator site on K2P channels.
|
| Cell Assay |
In vitro cell-based assays for BL-1249 include voltage-sensitive dye fluorescence assays and patch-clamp electrophysiology in cultured human bladder myocytes to assess channel activation. Cell viability and proliferation assays may also be conducted. The compound has been used as a TREK2 modulator in U-2 OS osteosarcoma cell lines. Concentration ranges typically span from low micromolar to higher concentrations depending on the assay format.
|
| Animal Protocol |
In vivo animal studies with BL-1249 have been conducted in rat models. Anesthetized rats received BL-1249 at 1 mg/kg via intravenous injection to assess effects on isovolumic contractions and blood pressure. The compound has also been used as a TREK1 and TREK2 activator in mice. Additional studies may involve mouse ileum and colon tissue contraction models. Dosing routes and regimens vary by experimental design.
|
| ADME/Pharmacokinetics |
Pharmacokinetic data for BL-1249 are not extensively documented in the available literature. The compound is a small molecule with molecular weight 291.35 and is soluble in DMSO (~17.5 mg/mL) but insoluble in water. It should be stored at -20°C and protected from light. Further PK parameters such as half-life, bioavailability, and clearance have not been reported.
|
| Toxicity/Toxicokinetics |
BL-1249 is classified as a non-steroidal anti-inflammatory drug. Hazard classifications include Eye Irrit. 2, Skin Irrit. 2, STOT SE 3, and Aquatic Chronic 4. The signal word is Warning. Standard laboratory safety precautions should be followed when handling this compound. It is not intended for human therapeutic use.
|
| References |
|
| Additional Infomation |
BL-1249 is featured on the Potassium Channels page of the Handbook of Receptor Classification and Signal Transduction. The compound is supplied as a pink to brown solid with purity ≥98% (HPLC). It is also referred to as (5,6,7,8-Tetrahydro-naphthalen-1-yl)-[2-(1H-tetrazol-5-yl)-phenyl]-amine. This compound is for research use only and not for therapeutic applications.
|
| Molecular Formula |
C17H17N5
|
|---|---|
| Molecular Weight |
291.36
|
| Exact Mass |
291.148
|
| CAS # |
18200-13-0
|
| Related CAS # |
18200-13-0
|
| PubChem CID |
16078951
|
| Appearance |
Off-white to light yellow solid powder
|
| Density |
1.291g/cm3
|
| Boiling Point |
492.6ºC at 760 mmHg
|
| Flash Point |
251.7ºC
|
| Vapour Pressure |
7.57E-10mmHg at 25°C
|
| Index of Refraction |
1.684
|
| LogP |
3.562
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
22
|
| Complexity |
363
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
YYNRZIFBTOUICE-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C17H17N5/c1-2-8-13-12(6-1)7-5-11-15(13)18-16-10-4-3-9-14(16)17-19-21-22-20-17/h3-5,7,9-11,18H,1-2,6,8H2,(H,19,20,21,22)
|
| Chemical Name |
5,6,7,8-Tetrahydro-N-[2-(2H-tetrazol-5-yl)phenyl]-1-naphthalenamine
|
| Synonyms |
BL1249 BL 1249 BL-1249
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~171.61 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.58 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 (8.58 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4322 mL | 17.1609 mL | 34.3218 mL | |
| 5 mM | 0.6864 mL | 3.4322 mL | 6.8644 mL | |
| 10 mM | 0.3432 mL | 1.7161 mL | 3.4322 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.
|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
