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| 25mg |
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Purity: =99.03%
Selonsertib (Also known as GS-4997) is a highly selective and potent once-daily orally available inhibitor of ASK1 (apoptosis signal-regulating kinase 1) with a pIC50 of 8.3±0.07. Selonsertib has been studied as a potential treatment for diabetic nephropathy and kidney fibrosis because of its potential anti-inflammatory, anti-cancer, and anti-fibrotic effects. A member of the mitogen-activated protein kinase family known as Apoptosis Signal-Regulating Kinase 1 (ASK1/MAP3K) has been linked to acute ischemia/reperfusion injury. Selonsertib was discovered using structure-based drug design, deconstruction, and reoptimization of a well-known ASK1 inhibitor. In a model of isolated perfused cardiac injury, selonsertib demonstrated potent inhibition of the MAP3K pathway and a reduction in the size of the infarct.
| Targets |
ASK1 (pIC50 = 8.3)
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| ln Vitro |
Selonsertib (GS-4997) is a clinical-stage ASK1 inhibitor that has been assessed as a potential treatment for kidney fibrosis and diabetic nephropathy[1]. A once-daily oral ASK1 inhibitor with high selectivity and potency, selonsertib (GS-4997), competes with ATP in the ASK1 catalytic kinase domain.
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| ln Vivo |
An oral bioavailable inhibitor of apoptosis signal-regulating kinase 1 (ASK1) that may have anti-inflammatory, anti-tumor, and anti-fibrotic properties. The ATP-competitive ASK1 inhibitor GS-4997 targets and binds to the catalytic kinase domain of ASK1 after oral administration, preventing its phosphorylation and activation. This stops downstream kinases, including p38 MAPK and c-Jun N-terminal kinases (JNKs), from becoming phosphorylated. GS-4997 inhibits cellular proliferation, down-regulates the expression of fibrosis-related genes, and suppresses excessive apoptosis by preventing the activation of ASK1-dependent signal transduction pathways[2]. Inflammatory cytokines are also prevented from being produced.
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| Enzyme Assay |
Selonsertib (Also known as GS-4997) is a highly selective and potent once-daily orally available ASK1 (apoptosis signal-regulating kinase 1) inhibitor that is highly potent and selective, with a pIC50 of 8.3–0.07. A once-daily oral ASK1 inhibitor with high selectivity and potency, selonsertib (GS-4997), competes with ATP in the catalytic kinase domain of ASK1.
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| Cell Assay |
An oral bioavailable inhibitor of apoptosis signal-regulating kinase 1 (ASK1) that may have anti-inflammatory, anti-tumor, and anti-fibrotic properties. The ATP-competitive ASK1 inhibitor GS-4997 targets and binds to the catalytic kinase domain of ASK1 after oral administration, preventing its phosphorylation and activation. This stops downstream kinases, including p38 MAPK and c-Jun N-terminal kinases (JNKs), from becoming phosphorylated. GS-4997 suppresses excessive apoptosis, inhibits cellular proliferation, down-regulates the expression of fibrosis-related genes, and prevents the production of inflammatory cytokines by preventing the activation of ASK1-dependent signal transduction pathways.
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| Animal Protocol |
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| References |
| Molecular Formula |
C24H24FN7O
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| Molecular Weight |
445.49
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| Exact Mass |
445.20
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| Elemental Analysis |
C, 64.71; H, 5.43; F, 4.26; N, 22.01; O, 3.59
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| CAS # |
1448428-04-3
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| Related CAS # |
1448428-04-3;1448428-05-4 (HCl);
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| Appearance |
White to off-white
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| SMILES |
CC1=CC(=C(C=C1N2C=C(N=C2)C3CC3)C(=O)NC4=CC=CC(=N4)C5=NN=CN5C(C)C)F
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| InChi Key |
YIDDLAAKOYYGJG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H24FN7O/c1-14(2)32-13-27-30-23(32)19-5-4-6-22(28-19)29-24(33)17-10-21(15(3)9-18(17)25)31-11-20(26-12-31)16-7-8-16/h4-6,9-14,16H,7-8H2,1-3H3,(H,28,29,33)
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| Chemical Name |
5-(4-cyclopropylimidazol-1-yl)-2-fluoro-4-methyl-N-[6-(4-propan-2-yl-1,2,4-triazol-3-yl)pyridin-2-yl]benzamide
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| Synonyms |
Selonsertib free base; GS-4997; GS4997; GS 4997; Selonsertib
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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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.62 mg/mL (5.88 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
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. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.67 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 20.8 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: ≥ 2.08 mg/mL (4.67 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. Solubility in Formulation 4: (saturation unknown) in (add these co-solvents sequentially from left to right, and one by one), |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2447 mL | 11.2236 mL | 22.4472 mL | |
| 5 mM | 0.4489 mL | 2.2447 mL | 4.4894 mL | |
| 10 mM | 0.2245 mL | 1.1224 mL | 2.2447 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02509624 | Completed | Drug: Selonsertib | Diabetic Kidney Disease | Gilead Sciences | August 18, 2015 | Phase 1 |
| NCT02854631 | Completed | Drug: Selonsertib Drug: Prednisolone |
Alcoholic Hepatitis (AH) |
Gilead Sciences | September 1, 2016 | Phase 2 |
| NCT02177786 | Completed | Drug: Selonsertib Drug: Placebo to match selonsertib |
Diabetic Kidney Disease | Gilead Sciences | June 2014 | Phase 2 |
| NCT04026165 | Completed | Drug: SEL Drug: Placebo |
Diabetic Kidney Disease | Gilead Sciences | July 24, 2019 | Phase 2 |
| NCT03449446 | Completed | Drug: SEL Drug: FIR |
Nonalcoholic Steatohepatitis | Gilead Sciences | March 21, 2018 | Phase 2 |
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