Garutadustat
Based on 1 Customer Validation
Garutadustat (ISM012-042) is an orally active, selective inhibitor of PHD1 and PHD2, with IC50 values of 1.9 nM and 2.5 nM, respectively. Garutadustat stabilizes HIF1α protein in intestinal epithelial cells, thereby activating gene transcription programs associated with mucus production, tight junction formation, anti-inflammatory mediator generation and wound healing, which fundamentally promotes mucosal barrier repair and regulates intestinal immunity. Garutadustat can be used for the research of inflammatory bowel disease.
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- Pureté: 98.78%
- CAS No.: 2924181-80-4
- Formule: C25H27N7O4
- Masse moléculaire:489.53
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Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
Description
In Vitro
Garutadustat (ISM012-042) (6 h) stabilizes HIF1α in Caco-2 HIF1α-HiBit cells with an EC50 value of 2.0 to 3.5 μM, and retains activity under different extracellular iron concentrations[1].
Garutadustat (2.5 μM; 0-96 h) protects Caco-2 cell monolayers against DSS (HY-116282C)-induced intestinal barrier disruption[1].
Garutadustat 2 (1-10 μM; 24 h) dose-dependently reduces the mRNA expression of proinflammatory cytokines IL-12p35 and TNF in LPS-stimulated mouse bone marrow-derived dendritic cells (BMDCs)[1].
Garutadustat (3 μM; 25 h) maintains the localization of ZO1 at intercellular junctions in Caco-2 cells and protects against DSS-induced tight junction disruption[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Murine bone marrow-derived dendritic cells (BMDCs) stimulated with lipopolysaccharide (LPS)
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Concentration:1, 3, 10 μM
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Incubation Time:24 h (concurrent with LPS stimulation)
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Result:Dose-dependently reduced IL-12p35 mRNA expression relative to LPS-stimulated vehicle controls.
Dose-dependently reduced TNF mRNA expression relative to LPS-stimulated vehicle controls.
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Cell Line:Caco-2 cells treated with DSS
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Concentration:3 μM
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Incubation Time:1 h pretreatment, then 24 h concurrent with DSS
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Result:Retained ZO1 at cell-cell contacts, preventing DSS-induced tight-junction disruption.
In Vivo
Garutadustat (1-10 mg/kg; p.o.; daily; 6-9 days) dose-dependently alleviates Oxazolone (HY-126360)-induced murine colitis (a model of T helper 2-driven disease) by reducing gut inflammation and restoring intestinal barrier function, with no systemic effects on EPO or VEGF levels[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c (female, 8 weeks old, ~19-21 g body weight, TNBS-induced colitis)[1]
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Dosage:1 mg/kg (prevention mode); 3 mg/kg (prevention mode; therapeutic mode); 10 mg/kg (prevention mode; therapeutic mode)
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Administration:p.o.; daily; 9 days (prevention mode: day -1 to day 7); 6 days (therapeutic mode: day 2 to day 7)
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Result:Reduced disease activity index (DAI) scores to levels comparable to 100 mg/kg mesalamine (3 and 10 mg/kg, prevention mode).
Reduced body weight loss, colon shortening, and colon weight (3 and 10 mg/kg, prevention mode).
Improved colonic histopathology scores (3 and 10 mg/kg, prevention mode).
Dose-dependently increased colon HIF1α staining intensity and mRNA expression of barrier-protective genes Tff3, Tjp1 and Nt5e (prevention mode).
Reduced plasma levels of proinflammatory cytokines IL-6 and TNF (prevention mode).
Reduced fecal lipocalin 2 (LCN2) and calprotectin levels (prevention mode).
Promoted weight gain and ameliorated disease severity within 48 hours (3 and 10 mg/kg, therapeutic mode).
Improved colonic gross pathology (3 and 10 mg/kg, therapeutic mode).
Reduced plasma fluorescein isothiocyanate (FITC)-dextran levels, indicating restored intestinal barrier function (3 and 10 mg/kg, therapeutic mode).
Reduced proportions of colonic lamina propria monocytes, neutrophils, and proinflammatory CD3+ T cell subsets (TNF+, IFNγ+, IL-17A+) relative to vehicle controls (3 and 10 mg/kg, therapeutic mode).
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Animal Model:BALB/c (female, 8 weeks old, ~18-20 g body weight, oxazolone-induced colitis)[1]
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Dosage:1 mg/kg (prevention mode); 3 mg/kg (prevention mode; therapeutic mode); 10 mg/kg (prevention mode; therapeutic mode)
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Administration:p.o.; daily; 9 days (prevention mode: day -1 to day 7); 6 days (therapeutic mode: day 2 to day 7)
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Result:Dose-dependently prevented body weight loss, improved DAI scores, improved colon density, and reduced fecal LCN2 levels (prevention mode).
Reduced colon tissue levels of proinflammatory chemokines (KC/GRO, MCP1, MIP1α, MIP2) and cytokines (IL-33, IL-5, IL-12p70, TNF) (prevention mode).
Reduced plasma IL-1β levels while leaving systemic EPO and VEGF levels unchanged (prevention mode).
Promoted disease remission, improved DAI scores, reduced plasma FITC-dextran levels (restored intestinal permeability), and normalized colon weight and length relative to vehicle controls (3 and 10 mg/kg, therapeutic mode).
Chemical Information
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CAS No. 2924181-80-4
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Appearance Solid
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Masse moléculaire 489.53
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Formule C25H27N7O4
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Color White to off-white
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SMILES
CC(C)(OC(N1CCN(C2=CC=C3C(C=NC(C(NCC4=CN=C(C#N)C=C4)=O)=C3O)=N2)CC1)=O)C
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Synonyms
ISM012-042
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
In Vitro:
DMSO : 25 mg/mL (51.07 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.11 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureté et documentation
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Fiche technique (277 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instruction de manipulation (2659 KB)
Références
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 2.0428 mL | 10.2139 mL | 20.4278 mL | 51.0694 mL |
| 5 mM | 0.4086 mL | 2.0428 mL | 4.0856 mL | 10.2139 mL | |
| 10 mM | 0.2043 mL | 1.0214 mL | 2.0428 mL | 5.1069 mL | |
| 15 mM | 0.1362 mL | 0.6809 mL | 1.3619 mL | 3.4046 mL | |
| 20 mM | 0.1021 mL | 0.5107 mL | 1.0214 mL | 2.5535 mL | |
| 25 mM | 0.0817 mL | 0.4086 mL | 0.8171 mL | 2.0428 mL | |
| 30 mM | 0.0681 mL | 0.3405 mL | 0.6809 mL | 1.7023 mL | |
| 40 mM | 0.0511 mL | 0.2553 mL | 0.5107 mL | 1.2767 mL | |
| 50 mM | 0.0409 mL | 0.2043 mL | 0.4086 mL | 1.0214 mL |
Garutadustat Related Classifications
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