| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
BI-9627 is a novel and highly potent NHE1 (sodium-hydrogen exchanger isoform 1) inhibitor with with an EC50 of 31 nM. It has good drug like properties such as high oral bioavailability, low DDI (drug drug interaction) potential, excellent pharmacokinetics, and good selectivity against NHE2 and NHE3. Sodium-hydrogen exchanger isoform 1 (NHE1) is a ubiquitously expressed transmembrane ion channel responsible for intracellular pH regulation. During myocardial ischemia, low pH activates NHE1 and causes increased intracellular calcium levels and aberrant cellular processes, leading to myocardial stunning, arrhythmias, and ultimately cell damage and death. The role of NHE1 in cardiac injury has prompted interest in the development of NHE1 inhibitors for the treatment of heart failure.
| Targets |
Sodium-hydrogen exchanger isoform 1 (NHE1) inhibitor (IC50 = 45 nM in pH change assay; EC50 = 241 nM in human platelet swelling assay) with >30-fold selectivity against NHE2 and no measurable inhibition of NHE3 up to 16 μM [1]
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| ln Vitro |
In the Langendorff isolated perfused rat heart model, BI-9627 significantly prevented ischemia-reperfusion injury, recovering left ventricular developed pressure (LVDP) to 100% and 36% of baseline at perfusate concentrations of 100 nM and 10 nM, respectively, measured 30 minutes post-reperfusion. It also significantly attenuated the increase in left ventricular end-diastolic pressure (LVEDP) compared to vehicle control [1]
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| Enzyme Assay |
NHE1 inhibition was assessed using a pH change assay in PS120 cells stably expressing human NHE1. Cells were loaded with the pH-sensitive dye BCECF-AM, acid-loaded with an NH₄Cl-containing buffer, and then exposed to compound-containing buffer lacking NH₄Cl. The recovery of intracellular pH was monitored fluorometrically, and IC₅₀ values were calculated as the concentration causing 50% inhibition of pH recovery [1]
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| Cell Assay |
Functional inhibition of NHE1 was evaluated using a human platelet swelling assay (hPSA). Platelet-rich plasma was incubated with compound and then exposed to a propionate medium to induce osmotic swelling. Swelling was measured as a decrease in optical density at 680 nm over time, and EC₅₀ values were derived from the inhibition of swelling [1]
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| Animal Protocol |
Pharmacokinetic studies in rats: BI-9627 was dissolved in 20% hydroxypropyl-β-cyclodextrin for intravenous dosing (1 mg/kg) and suspended in 0.015% Tween 80 + 0.5% aqueous methylcellulose for oral dosing (5 mg/kg) to fasted male Sprague-Dawley rats. Serial blood samples were collected up to 24 hours for plasma analysis by LC/MS/MS [1]
Pharmacokinetic studies in dogs: Similar formulations were used in male Beagle dogs following 1 mg/kg iv or 5 mg/kg po dosing, with blood sampling up to 72 hours [1] |
| ADME/Pharmacokinetics |
In rats, BI-9627 was cleared at a low rate (5.7% of hepatic blood flow), with a volume of distribution of 0.76 L/kg, a mean residence time of 3.2 hours, and an oral bioavailability of 73% [1]. In dogs, it was cleared at a rate of 36.2% of hepatic blood flow, with a volume of distribution of 1.4 L/kg, a mean residence time of 2.1 hours, and an oral bioavailability of 33% [1]. The drug exhibits low inhibition of CYP enzymes (IC₅₀ > 30 µM for 2C19, 2C9, 2D6, and 3A4), high metabolic stability in human and rat liver microsomes (QH < 11% and 11%, respectively), and high membrane permeability as measured by PAMPA [1].
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| Toxicity/Toxicokinetics |
BI-9627 showed no mutagenicity at concentrations up to 5000 µg/well in the Ames assay (regardless of S9 activation); no cytotoxicity at concentrations up to 100 µM in HeLa cells; and no incidence of phospholipid deposition at concentrations up to 50 µM in the Nile Red assay [1]. It does not inhibit hERG channels (IC₅₀ > 30 µM in the PatchXpress assay) and showed no time-dependent inactivation of CYP3A4 at concentrations up to 50 µM [1].
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| References | |
| Additional Infomation |
BI-9627 is an optimized NHE1 inhibitor derived from sapipole, designed for once-daily oral administration, with a low risk of drug interactions and improved pharmacokinetic properties, and is indicated for the treatment of chronic heart failure [1].
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| Molecular Formula |
C16H19F3N4O2
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|---|---|
| Molecular Weight |
356.342873811722
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| Exact Mass |
356.146
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| CAS # |
1204329-34-9
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| Related CAS # |
BI-9627 hydrochloride;1422252-46-7
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| PubChem CID |
51031001
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| Appearance |
White to yellow solid powder
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| LogP |
1.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
25
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| Complexity |
538
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(NC(N)=N)(=O)C1=CC=C(C2CCN(C(C)=O)CC2)C(C(F)(F)F)=C1
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| InChi Key |
QMHRLXNEGYTSRV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H19F3N4O2/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)
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| Chemical Name |
4-(1-acetylpiperidin-4-yl)-N-(diaminomethylidene)-3-(trifluoromethyl)benzamide
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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 (~280.63 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.84 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 20.8 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: ≥ 2.08 mg/mL (5.84 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 20.8 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: ≥ 2.08 mg/mL (5.84 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 | 2.8063 mL | 14.0315 mL | 28.0631 mL | |
| 5 mM | 0.5613 mL | 2.8063 mL | 5.6126 mL | |
| 10 mM | 0.2806 mL | 1.4032 mL | 2.8063 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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