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Purity: ≥98%
SBI-115 (SBI115) is a novel and potent TGR5 (GPCR19) antagonist with the potential to be used for polycystic liver disease. In polycystic liver diseases, it reduces hepatic cystogenesis by blocking TGR5. By boosting cholangiocyte proliferation and cAMP levels, TGR5 aids in the process of hepatic cystogenesis1. A TGR5 antagonist, either by itself or in combination with somatostatin receptor agonists, may be a useful treatment option for polycystic liver disease. TGR5 promotes hepatic cystogenesis by elevating cAMP and cholangiocyte proliferation.
| Targets |
TGR5
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|---|---|
| ln Vitro |
SBI-115 (100-200 μM, 24 hours) prevents the proliferation of shRNA-transfected ADPKD cholangiocytes that is caused by pre-treating cystic cholangiocytes with taurolithocholic acid (TLCA)[1].
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| ln Vivo |
In order to further investigate TGR5's role in PLD, we produced double-mutant mice with the TGR5−/−;Pkhd1del2/del2 phenotype. TGR5−/− mice demonstrated good health and reproducibility, in line with an earlier report. 29, Overall morphology (Supporting Fig. 4), liver, cholangiocyte, and primary cilium morphology (Supporting Table 4), and serum biochemistries (Supporting Table 3) were similar in WT and TGR5−/− mice. More than one hepatic cyst is present in Pkhd1del2/del2 rodents. 30, TGR5 was overexpressed in Pkhd1del2/del2 mice relative to WT, while it was not seen in TGR5−/− mice or TGR5−/−;Pkhd1del2/del2 mice, which is in line with our findings in other animal models of PLD (Supporting Fig. 5). Compared to Pkhd1del2/del2 littermates, we observed reductions in liver weight (30%), hepatic cystic areas (31%), and hepatic fibrotic areas (33%), in double mutant TGR5−/−;Pkhd1del2/del2 mice (both males and females). * Supporting Table 4 and Figure 5A. The mouse serum biochemistries in each group were comparable (Supporting Table 3). Reduced quantity of PCNA-positive nuclei by three times was linked to attenuated hepatic cystogenesis in double mutant TGR5−/−;Pkhd1del2/del2 mice (Fig. 5B).
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| Cell Assay |
Cell Line: shRNA-transfected ADPKD cholangiocytes
Concentration: 100, 200 µM Incubation Time: 24 hours Result: Inhibited proliferation (by 32-48%) triggered by pre-treatment of cystic cholangiocytes with TLCA. |
| References |
| Molecular Formula |
C14H13CLN2O4S
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|---|---|
| Molecular Weight |
340.782021284103
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| Exact Mass |
340.03
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| Elemental Analysis |
C, 49.34; H, 3.85; Cl, 10.40; N, 8.22; O, 18.78; S, 9.41
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| CAS # |
882366-16-7
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| PubChem CID |
18879973
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| Appearance |
White to off-white solid powder
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
22
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| Complexity |
494
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
IJPXOPBVXVPPEW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H13ClN2O4S/c1-3-22(19,20)14-16-8-11(15)12(17-14)13(18)21-10-6-4-5-9(2)7-10/h4-8H,3H2,1-2H3
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| Chemical Name |
(3-methylphenyl) 5-chloro-2-ethylsulfonylpyrimidine-4-carboxylate
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| Synonyms |
SBI115; SBI 115; SBI-115
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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: 68~150 mg/mL (199.5~440.2 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 3 mg/mL (8.80 mM) in 2% DMSO + 40% PEG300 + 5% Tween80 + 53% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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 (7.34 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.34 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 5 mg/mL (14.67 mM) in Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9344 mL | 14.6722 mL | 29.3444 mL | |
| 5 mM | 0.5869 mL | 2.9344 mL | 5.8689 mL | |
| 10 mM | 0.2934 mL | 1.4672 mL | 2.9344 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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