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| Targets |
SLC26A3-IN-2 specifically targets SLC26A3 (Down-Regulated in Adenoma), an anion exchanger protein belonging to the solute carrier (SLC) family SLC26. SLC26A3 plays a crucial role in intestinal physiology by mediating the electroneutral exchange of chloride (Cl-) and bicarbonate (HCO3-). By inhibiting SLC26A3 with an IC50 of 360 nM, this compound blocks this exchange process, which alters the ionic composition and fluidity of the intestinal contents..
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| ln Vitro |
Compound 3a, SLC26A3-IN-2, inhibits SLC26A3 by 92% at 10 μM for 10 minutes[1].
In vitro, SLC26A3-IN-2 is an orally active inhibitor of the anion exchanger protein SLC26A3. It has an IC50 of 360 nM, indicating a strong affinity for the transporter at sub-micromolar concentrations.. This activity is selective for SLC26A3, which distinguishes it from other transporters in the SLC26 family that have broad anion specificity for chloride, bicarbonate, sulfate, and oxalate. By inhibiting this exchanger, the compound can increase the chloride content and reduce the pH of the intestinal lumen, leading to the secretion of water. |
| ln Vivo |
In a mouse constipation paradigm caused by Loperamide, SLC26A3-IN-2 (10 mg/kg; oral) dramatically increased the weight and number of feces, indicating that it is effective in enhancing fecal hydration in mice [1].
In vivo, SLC26A3-IN-2 has been shown to have significant gastrointestinal effects. At an oral dose of 10 mg/kg, it significantly increases stool weight and the number of fecal pellets in a Loperamide-induced constipation mouse model.. This demonstrates that the compound is effective in vivo at promoting intestinal motility and water content, which supports its potential mechanism as a pro-secretory agent for treating constipation. The effect is consistent with the pharmacological inhibition of Cl-/HCO3- exchange. |
| Enzyme Assay |
The standard in vitro protocol for assessing SLC26A3 inhibition is a radiolabeled anion exchange assay. COS-7 or HEK-293 cells are transiently transfected with the human SLC26A3 (DRA) cDNA. After 48-72 hours, the cells are harvested and seeded into 24-well plates. The cells are washed with a chloride-free buffer. Varying concentrations of SLC26A3-IN-2 (0.1-1000 nM) are added to the cells and pre-incubated for 15 minutes. To measure exchange, the cells are incubated with a chloride-containing buffer spiked with [3⁶Cl]- (sodium chloride, 1 uCi/well). After a 5-minute incubation, the uptake reaction is terminated by washing the cells three times with ice-cold PBS. The cells are lysed with 0.2 N NaOH, and the radioactivity is counted in a liquid scintillation counter. The IC50 (360 nM) is calculated from the dose-response curve..
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| Cell Assay |
The in vitro cellular assay for SLC26A3-IN-2 utilizes T84 human colonic carcinoma cells, which endogenously express high levels of SLC26A3. Cells are seeded on permeable Transwell supports and cultured until they form polarized monolayers with high transepithelial electrical resistance (TEER > 500 omega·cm2). The filter inserts are mounted in Ussing chambers to measure short-circuit current (Isc), a continuous measurement of ion transport across the epithelium. The mucosal and serosal sides are bathed in a bicarbonate-buffered Ringers solution. The preparation is voltage-clamped, and SLC26A3 activity is stimulated by establishing an apical-to-basolateral chloride gradient. Varying concentrations of SLC26A3-IN-2 (0.1-1000 nM) are added to the apical (mucosal) side. The reduction in the CI-/HCO3- exchange current (deltaIsc) is recorded, and the IC50 is calculated from the dose-response curve.
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| Animal Protocol |
An in vivo protocol for SLC26A3-IN-2 uses a Loperamide-induced constipation mouse model to measure the compound‘s efficacy on gastrointestinal motility. Male ICR mice (6-8 weeks old, 20-25 g) are fasted for 18 hours. Loperamide (5 mg/kg) is administered orally to induce constipation. Thirty minutes later, SLC26A3-IN-2 is dissolved in a suitable vehicle (e.g., 5% DMSO/40% PEG300/5% Tween-80/50% ddH2O) and administered orally by gavage at doses of 3, 10, and 30 mg/kg. Control groups receive vehicle or the known pro-kinetic agent (e.g., prucalopride). After administration, the mice are placed in individual cages with absorbent paper. The number of fecal pellets and total stool weight are recorded at 1, 2, 4, and 6 hours post-dosing. The colon is removed at the end of the study, and the water content of the feces is measured by comparing wet weight versus dry weight after overnight lyophilization. The compound should increase both the number and water content of the fecal pellets..
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) data for SLC26A3-IN-2 is not provided. It is described as an orally active inhibitor, indicating it has sufficient oral bioavailability. A standard PK study in mice would involve oral (PO) administration (10 mg/kg) and intravenous (IV) administration (1 mg/kg). Blood samples would be collected at multiple time points (0-24 h), and plasma concentrations of the compound would be quantified by LC-MS/MS. Key parameters, including T1/2, Cmax, AUC, and oral bioavailability (F%), would be determined. The compound likely has a low volume of distribution and is primarily metabolized by the liver. Given its mechanism, it is expected to concentrate in the gastrointestinal tract.
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| Toxicity/Toxicokinetics |
Specific toxicological data for SLC26A3-IN-2 is not available. The primary safety concern for a SLC26A3 inhibitor is the potential for secretory diarrhea and associated electrolyte imbalances. Chronic stimulation of chloride and water secretion could lead to dehydration, hypokalemia, and hyperchloremic metabolic acidosis. Standard safety assessment would include a 14-day repeat-dose oral toxicity study in rats to determine the Maximum Tolerated Dose (MTD) and the No-Observed-Adverse-Effect Level (NOAEL). Key endpoints would include monitoring of fecal consistency, body weight, food consumption, and clinical biochemistry (electrolytes, blood urea nitrogen, creatinine). Histopathological examination of the gastrointestinal tract would assess for evidence of inflammation or epithelial damage.
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| References | |
| Additional Infomation |
SLC26A3-IN-2 is a research-grade chemical and is not approved for clinical use. SLC26A3 (Down-Regulated in Adenoma, DRA) is an anion exchanger highly expressed in the ileum and colon, and its inhibition increases luminal chloride and water content. This makes SLC26A3-IN-2 a valuable tool for studying the pathophysiology of constipation, inflammatory bowel disease, and other gastrointestinal motility disorders. It is for research use only.
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| Molecular Formula |
C19H13CLN2O2S
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| Molecular Weight |
368.836722135544
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| Exact Mass |
368.038
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| CAS # |
950348-60-4
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| PubChem CID |
16009351
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| Appearance |
White to off-white solid powder
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| LogP |
3.9
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
625
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)C2=CSC3=NC(=CC(=O)N23)COC4=CC=CC=C4Cl
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| InChi Key |
MXPJASIJFFIVEL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H13ClN2O2S/c20-15-8-4-5-9-17(15)24-11-14-10-18(23)22-16(12-25-19(22)21-14)13-6-2-1-3-7-13/h1-10,12H,11H2
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| Chemical Name |
7-[(2-chlorophenoxy)methyl]-3-phenyl-[1,3]thiazolo[3,2-a]pyrimidin-5-one
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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: 16.67 mg/mL (45.20 mM)
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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 | 2.7112 mL | 13.5560 mL | 27.1120 mL | |
| 5 mM | 0.5422 mL | 2.7112 mL | 5.4224 mL | |
| 10 mM | 0.2711 mL | 1.3556 mL | 2.7112 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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