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S0859 (S-0859) is an N-cyanosulphonamide compound acting as a novel, selective, high-affinity generic inhibitor of NBC [(Na(+)-coupled HCO(3)(-) transporters]. It is potentially important for probing the transporter's functional role in heart and other tissues. S0859 reversibly inhibited NBC-mediated pH(i) recovery (K (i)=1.7 microM, full inhibition at approximately 30 microM). In HEPES-buffered superfusates, NHE-mediated pH(i) recovery was unaffected by 30 microM S0859. With CO(2)/HCO(3) (-) buffer, pH(i) recovery from intracellular alkalosis (mediated by Cl(-)/HCO(3) (-) and Cl(-)/OH(-) exchange) was also unaffected. The time course of recovery of pH(i) and contraction was slowed by S0859, confirming that NBC is a significant controller of contractility during acidosis.
| Targets |
S0859 targets sodium bicarbonate cotransporters (NBCs), specifically NBCn1 (SLC4A7) (IC50 = 0.4 μM in HEK293 cells overexpressing human NBCn1; IC50 = 0.6 μM in rat coronary endothelial cells) [3][4]
S0859 shows no significant affinity for Na+/H+ exchanger 1 (NHE1) (IC50 > 30 μM) [2][4] |
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| ln Vitro |
When NBC inhibitor S0859 was administered, caspase-3 activity and the quantity of apoptotic EC were both markedly increased. S0859 may be crucial for examining the functional role of the transporter in the heart and other tissues[1].
In HEK293 cells overexpressing human NBCn1, S0859 (0.1-10 μM) dose-dependently inhibited HCO3⁻-dependent pH recovery, with an IC50 of 0.4 μM; maximal inhibition (≥90%) was achieved at 5 μM [4] - In MCF7 breast cancer cells (wild-type and ErbB2-overexpressing), S0859 (1-30 μM) did not affect cell proliferation but significantly inhibited cell migration: at 10 μM, migration was reduced by ~40% (wild-type) and ~35% (ErbB2-overexpressing) compared to vehicle, as measured by transwell assay [2] - In human breast cancer cells (MDA-MB-231, BT-474), S0859 (5-20 μM) dose-dependently inhibited sodium bicarbonate cotransport activity, with IC50 values of 3.2 μM (MDA-MB-231) and 2.8 μM (BT-474); this was associated with reduced intracellular pH (pHi) alkalinization (from 7.45 ± 0.05 to 7.21 ± 0.04 at 10 μM) [1] - In rat coronary endothelial cells (CECs) subjected to hypoxia-reoxygenation (H/R) injury, S0859 (0.5-5 μM) dose-dependently reduced mitochondrial apoptosis: at 2 μM, caspase-3 activity was decreased by ~55%, and Bcl-2/Bax ratio was increased by 2.3-fold compared to H/R alone; intracellular ROS production was also reduced by ~40% [3] - S0859 (up to 30 μM) showed no significant inhibition of NHE1 activity in A549 cells, confirming selectivity for NBCs over NHE1 [4] |
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| ln Vivo |
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| Enzyme Assay |
NBCn1-mediated HCO3⁻ transport assay (pH-sensitive dye): HEK293 cells overexpressing human NBCn1 were seeded in 96-well plates and loaded with the pH-sensitive fluorescent dye BCECF-AM for 30 minutes at 37°C. Cells were acidified by NH4Cl prepulse, then exposed to HCO3⁻-containing buffer with serial dilutions of S0859. Fluorescence intensity (excitation 440/490 nm, emission 535 nm) was monitored to measure pH recovery rate, reflecting NBCn1 activity. IC50 values were calculated by nonlinear regression of dose-response curves [4]
- Sodium bicarbonate cotransport assay (radioactive tracer): MDA-MB-231 cells were seeded in 24-well plates and preincubated with S0859 (0.1-30 μM) for 30 minutes. Cells were then incubated with 14C-labeled HCO3⁻ for 15 minutes at 37°C. Unincorporated tracer was removed by washing, and cell-associated radioactivity was measured using a scintillation counter. Inhibition rates were calculated relative to vehicle control [1] |
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| Cell Assay |
Breast cancer cell migration assay: MCF7 cells (wild-type or ErbB2-overexpressing) were seeded in the upper chamber of transwell inserts (8 μm pores) at 5×10⁴ cells/well. S0859 (1-30 μM) was added to both upper and lower chambers, and cells were incubated for 24 hours. Migrated cells were fixed, stained with crystal violet, and counted under a microscope; migration rate was normalized to vehicle control [2]
- Intracellular pH (pHi) measurement: BT-474 cells were loaded with BCECF-AM for 30 minutes, then treated with S0859 (5-20 μM) for 1 hour. pHi was calculated from fluorescence ratios (490/440 nm excitation) using a calibration curve generated with high-K+ buffers of known pH [1] - Hypoxia-reoxygenation (H/R) apoptosis assay: Rat coronary endothelial cells were seeded in 6-well plates and treated with S0859 (0.5-5 μM) for 1 hour before exposure to hypoxia (1% O2) for 4 hours, followed by reoxygenation (21% O2) for 24 hours. Apoptosis was assessed by Annexin V-FITC/PI staining and flow cytometry; caspase-3 activity was measured using a colorimetric assay kit [3] - Western blot assay: H/R-treated coronary endothelial cells were lysed in RIPA buffer, and proteins were separated by SDS-PAGE. Membranes were probed with antibodies against Bcl-2, Bax, cleaved caspase-3, and GAPDH (loading control). Chemiluminescent detection and densitometric analysis were used to quantify protein expression [3] - NHE1 selectivity assay: A549 cells were loaded with BCECF-AM and acidified by NH4Cl prepulse. Na+-dependent pH recovery (mediated by NHE1) was measured in the presence of S0859 (1-30 μM) or NHE1 inhibitor EIPA (positive control). Fluorescence intensity was monitored to assess NHE1 activity [4] |
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| Animal Protocol |
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| Toxicity/Toxicokinetics |
In vitro cytotoxicity: As determined by the MTT assay, treatment with S0859 at concentrations up to 30 μM for 72 hours did not affect the viability of MCF7, MDA-MB-231, BT-474, or coronary endothelial cells [1][2][3]
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| References |
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| Additional Infomation |
S0859 is a selective small-molecule sodium-bicarbonate cotransporter (NBC) inhibitor belonging to the N-cyanosulfonamide class of compounds [4]. The main mechanism of action of S0859 is to inhibit NBC-mediated HCO3⁻ influx, thereby reducing intracellular pH (pHi) and regulating pH-dependent cellular processes such as cell migration and mitochondrial apoptosis [1][3][4]. S0859 has a much higher selectivity for NBCn1 (SLC4A7) than other acid-base transporters (such as NHE1), making it a valuable tool compound for studying the function of NBC in cancer and cardiovascular biology [2][4]. Preclinical in vitro data suggest that S0859 has potential applications in the treatment of breast cancer (by inhibiting cell migration) and ischemic cardiovascular disease (by protecting endothelial cells from apoptosis) [1][2][3].
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| Molecular Formula |
C29H24CLN3O3S
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| Molecular Weight |
530.04
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| Exact Mass |
529.122
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| CAS # |
1019331-10-2
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| Related CAS # |
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| PubChem CID |
70675849
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| Appearance |
White to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
748.5±70.0 °C at 760 mmHg
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| Flash Point |
406.5±35.7 °C
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| Vapour Pressure |
0.0±2.5 mmHg at 25°C
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| Index of Refraction |
1.639
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| LogP |
5.68
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
37
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| Complexity |
897
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ITDBPOSLOROLMT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H24ClN3O3S/c1-21-10-12-22(13-11-21)18-33(29(34)26-7-2-4-8-27(26)30)19-23-14-16-24(17-15-23)25-6-3-5-9-28(25)37(35,36)32-20-31/h2-17,32H,18-19H2,1H3
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| Chemical Name |
2-chloro-N-[[4-[2-(cyanosulfamoyl)phenyl]phenyl]methyl]-N-[(4-methylphenyl)methyl]benzamide
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.72 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 (4.72 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 (4.72 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 | 1.8867 mL | 9.4333 mL | 18.8665 mL | |
| 5 mM | 0.3773 mL | 1.8867 mL | 3.7733 mL | |
| 10 mM | 0.1887 mL | 0.9433 mL | 1.8867 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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