| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg | |||
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| Targets |
BIX HCl selectively targets the sodium-hydrogen exchanger isoform 1 (NHE1), a membrane transport protein that regulates intracellular pH by exchanging extracellular sodium for intracellular protons. NHE1 plays a critical role in maintaining cellular pH homeostasis and is involved in cell volume regulation, proliferation, and survival. By inhibiting NHE1, BIX HCl prevents the extrusion of protons, leading to intracellular acidification. This inhibition is particularly relevant in ischemia-reperfusion injury, where NHE1 activation contributes to cellular damage.
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| ln Vitro |
In vitro, BIX HCl is a potent inhibitor of NHE1 with IC50 values of 6 nM in intracellular pH restoration assays and 31 nM in human platelet swelling assays. It displays more than 30-fold selectivity for NHE1 over NHE2 and has no obvious inhibitory activity against NHE3. The compound also displays low drug-drug interaction (DDI) potential. Its high potency and selectivity make it a valuable tool for studying the physiological and pathophysiological roles of NHE1.
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| ln Vivo |
In vivo, BIX HCl has demonstrated significant efficacy in an isolated cardiac ischemia-reperfusion injury model. It prevents ischemic damage in an ischemia-reperfusion injury isolated rat heart model ex vivo. The compound shows good pharmacokinetics in rats and dogs. These results suggest that NHE1 inhibition by BIX HCl is cardioprotective, and the compound may have therapeutic potential for conditions involving ischemia-reperfusion injury, such as myocardial infarction and stroke.
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| Enzyme Assay |
Non-cellular in vitro assays for BIX HCl involve measuring its inhibition of NHE1 activity in membrane preparations. A typical protocol uses cells overexpressing NHE1, from which membrane vesicles are prepared. The vesicles are loaded with a pH-sensitive fluorescent dye (e.g., BCECF). The dye-loaded vesicles are suspended in a buffer, and the fluorescence is monitored. The rate of pH recovery upon the addition of extracellular sodium is measured. Varying concentrations of BIX HCl are added, and the inhibition of pH recovery is calculated. The IC50 is determined from the concentration-response curve.
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| Cell Assay |
Cellular assays for BIX HCl are performed using cells endogenously expressing NHE1, such as human platelets or fibroblasts. For the intracellular pH restoration assay, cells are acid-loaded using a nigericin-based technique or by ammonium chloride prepulse. The cells are then placed in a sodium-containing buffer, and the recovery of intracellular pH is monitored using a pH-sensitive fluorescent dye (e.g., BCECF-AM). The inhibition of pH recovery by BIX HCl is measured. For the platelet swelling assay, human platelets are incubated with BIX HCl, and the swelling induced by hypotonic shock is measured.
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| Animal Protocol |
In vivo animal studies for BIX HCl are conducted in rat models of cardiac ischemia-reperfusion injury. Rats undergo surgical occlusion of the left anterior descending coronary artery to induce ischemia, followed by reperfusion. BIX HCl is administered intravenously or orally prior to ischemia or at the time of reperfusion. Infarct size is measured by triphenyltetrazolium chloride (TTC) staining. Cardiac function is assessed by echocardiography. The compound's ability to reduce infarct size and improve cardiac function is evaluated.
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| ADME/Pharmacokinetics |
BIX HCl has a molecular weight of 392.80 and is soluble in DMSO at ~100 mg/mL and in water at ~4.17 mg/mL. For in vivo studies, it can be formulated in vehicles such as 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline to achieve a solubility of ≥ 2.5 mg/mL. The compound shows good pharmacokinetics in rats and dogs, indicating favorable absorption, distribution, metabolism, and excretion (ADME) properties. It is stored as a powder at -20°C for up to 3 years.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for BIX HCl have not been extensively reported. As a research chemical, it is not intended for human use and is strictly for preclinical research purposes. Standard safety precautions should be followed when handling BIX HCl, including the use of personal protective equipment. The compound is typically stored as a powder at -20°C for up to three years or at 4°C for up to two years. No specific toxicity data, such as LD50 values, are available in the provided literature.
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| References | |
| Additional Infomation |
BIX HCl (BI-9627 hydrochloride) is a potent and selective NHE1 inhibitor. It is a valuable pharmacological tool for studying the role of NHE1 in pH regulation, cell volume control, and ischemia-reperfusion injury. The compound's high potency (IC50 = 6 nM in pHi assays) and selectivity over NHE2 and NHE3 make it a useful probe for dissecting NHE1-specific functions. BIX HCl is not a clinically approved drug and has not entered clinical trials. Its primary application is in academic and pharmaceutical research to validate NHE1 as a therapeutic target for cardiovascular diseases.
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| Molecular Formula |
C16H20CLF3N4O2
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|---|---|
| Molecular Weight |
392.803812980652
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| Exact Mass |
392.122
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| CAS # |
1422252-46-7
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| Related CAS # |
BI-9627;1204329-34-9
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| PubChem CID |
121513866
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| Appearance |
Off-white to light yellow solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
26
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| Complexity |
538
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.FC(C1C=C(C(/N=C(\N)/N)=O)C=CC=1C1CCN(C(C)=O)CC1)(F)F
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| InChi Key |
SLSZLEROFKLICF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H19F3N4O2.ClH/c1-9(24)23-6-4-10(5-7-23)12-3-2-11(14(25)22-15(20)21)8-13(12)16(17,18)19;/h2-3,8,10H,4-7H2,1H3,(H4,20,21,22,25);1H
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| Chemical Name |
4-(1-acetylpiperidin-4-yl)-N-(diaminomethylidene)-3-(trifluoromethyl)benzamide;hydrochloride
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| Synonyms |
BIX HCl
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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: Please store this product in a sealed and protected environment, 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 (~254.58 mM)
H2O : ~4.17 mg/mL (~10.62 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.36 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 (6.36 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 (6.36 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 | 2.5458 mL | 12.7291 mL | 25.4582 mL | |
| 5 mM | 0.5092 mL | 2.5458 mL | 5.0916 mL | |
| 10 mM | 0.2546 mL | 1.2729 mL | 2.5458 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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