| Size | Price | Stock | Qty |
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| 10mg |
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| Targets |
Bile salt hydrolase (BSH)[1]
GR-7 targets bile salt hydrolase (BSH), an enzyme produced by certain gut bacteria that deconjugates bile acids. It is a covalent inhibitor that acts on a broad range of BSHs (pan-BSH inhibitor), effectively reducing the activity of these enzymes in the gut. By inhibiting BSH, it prevents the deconjugation of bile acids, thereby altering the bile acid pool in the intestine. |
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| ln Vitro |
The epithelial barrier integrity of Caco-2 cells was not affected by the BSH Inhibitor Gut Restricted-7 (GR-7) (60 μM), suggesting that this molecule is comparatively benign. Additionally, microbial biomass is unaffected by gut restricted-7 [1].
In vitro, Gut restricted-7 (60 μM) does not affect the epithelial barrier integrity of Caco-2 cells and does not impact microbial biomass. This indicates that the compound is relatively benign to host cells and the overall microbial community. Its specificity for bacterial BSH over host enzymes is a key feature of its design. |
| ln Vivo |
For one day, C57BL/6 mice were given either a powdered food that contained 0.09% of Gut Restricted-7 (GR-7) (w/w) or just the powdered diet. Eight hours after a food shift, gut restricted-7 dramatically reduced BSH activity in the excrement of mice treated with inhibitors. Cecal contents contained 20 pmol/mg wet weight (~20 μM) of gut restricted-7 [1].
In vivo, C57BL/6 mice fed a powdered diet containing 0.09% Gut restricted-7 (w/w) for one day showed significantly inhibited fecal BSH activity 8 hours after the diet change. The concentration of GR-7 in cecal contents was detected at 20 pmol/mg wet weight (~20 μM). These results confirm its oral bioavailability and efficacy in the gut. |
| Enzyme Assay |
Non-cellular enzyme assays for GR-7 would involve measuring its inhibitory activity against purified bile salt hydrolase (BSH) enzymes. The compound would be incubated with the enzyme and a substrate, and the inhibition of enzymatic activity would be quantified to determine its potency as a covalent BSH inhibitor. Its pan-BSH activity can be confirmed by testing against a panel of BSH enzymes from different bacterial species.
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| Cell Assay |
In vitro cellular assays for GR-7 are performed using Caco-2 cells to assess its effects on epithelial barrier integrity. Cells are treated with the compound, and the integrity of the monolayer is measured by assessing transepithelial electrical resistance (TEER) or permeability to fluorescent markers. Its lack of effect on microbial biomass can be confirmed by culturing fecal microbiota in the presence of the compound.
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| Animal Protocol |
In vivo animal experiments for GR-7 are conducted in C57BL/6 mice. The compound is administered orally via the diet at 0.09% (w/w). The primary endpoints are the measurement of BSH activity in fecal samples and the quantification of deconjugated bile acid levels. The gut-restricted nature of the compound can be confirmed by measuring its concentration in plasma and other tissues.
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| ADME/Pharmacokinetics |
GR-7 has a molecular weight of 510.64 and a molecular formula of C25H40FNaO6S. Its CAS number is 2553218-46-3. It is soluble in DMSO (250 mg/mL) and H2O (100 mg/mL). For in vivo studies, it can be formulated in 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% Saline. It is typically stored as a powder at -20°C.
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| Toxicity/Toxicokinetics |
Toxicological data for GR-7 are limited, but in vitro studies indicate that it does not affect the epithelial barrier integrity of Caco-2 cells at 60 μM, suggesting low cytotoxicity. The compound also does not alter microbial biomass, indicating a targeted effect on BSH activity rather than broad antimicrobial activity. Its gut-restricted nature further minimizes systemic exposure and potential off-target toxicity.
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| References |
[1]. Adhikari AA, et al. Development of a covalent inhibitor of gut bacterial bile salt hydrolases. Nat Chem Biol. 2020 Mar;16(3):318-326.
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| Additional Infomation |
GR-7 is a covalent and orally active pan-BSH inhibitor. It is a research compound used to study the role of the gut microbiome in metabolism, particularly the deconjugation of bile acids. No clinical trial or regulatory approval information is available in the search results.
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| Molecular Formula |
C25H40FNAO6S
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|---|---|
| Exact Mass |
510.242
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| CAS # |
2553218-46-3
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| Related CAS # |
BSH-IN-1;2553217-91-5
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| PubChem CID |
145713840
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
34
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| Complexity |
849
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| Defined Atom Stereocenter Count |
10
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| SMILES |
C[C@H](CCC(=O)CF)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2[C@@H](C[C@H]4[C@@]3(CC[C@H](C4)OS(=O)(=O)[O-])C)O)C.[Na+]
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| InChi Key |
GVCGSXGVFOXFAT-CTSSCMOWSA-M
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| InChi Code |
InChI=1S/C25H41FO6S.Na/c1-15(4-5-17(27)14-26)19-6-7-20-23-21(9-11-25(19,20)3)24(2)10-8-18(32-33(29,30)31)12-16(24)13-22(23)28;/h15-16,18-23,28H,4-14H2,1-3H3,(H,29,30,31);/q;+1/p-1/t15-,16+,18-,19-,20+,21+,22-,23+,24+,25-;/m1./s1
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| Chemical Name |
sodium;[(3R,5R,7R,8R,9S,10S,13R,14S,17R)-17-[(2R)-6-fluoro-5-oxohexan-2-yl]-7-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl] sulfate
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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: 250 mg/mL (489.59 mM)
H2O: ≥ 100 mg/mL (195.84 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.19 mg/mL (4.29 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 21.9 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 (4.07 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 (4.07 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
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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