| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Interleukin-1 receptor-associated kinase 4 (IRAK4): Selective inhibitor with an IC50 of 0.1 μM in kinase assays [1].
IRAK4 (Interleukin-1 receptor-associated kinase 4) (IC₅₀ = 0.6 nM in biochemical assay; EC₅₀ = 15 nM in cell-based assay) [1,2] |
|---|---|
| ln Vitro |
- Potent IRAK4 Inhibition: Edecesertib (GS-5718) demonstrated IC₅₀ = 0.6 nM in IRAK4 kinase activity assay and EC₅₀ = 15 nM in human whole blood cell assay, potently blocking TNF-α production [1,2]
- Selectivity Profile: At 1000 nM, Edecesertib showed >500-fold selectivity against 72 kinases except IRAK1 (176-fold selectivity), with IRAK1 IC₅₀ = 70 nM [1] - Anti-Inflammatory Activity: In LPS-stimulated THP-1 macrophages, Edecesertib (10 μM) reduced IL-6 and IL-1β secretion by 82% and 75%, respectively, via suppression of NF-κB pathway activation [1] |
| ln Vivo |
- Efficacy in Lupus Model: In NZB/W F1 mice (a lupus model), Edecesertib (30 mg/kg, p.o.) administered daily for 28 days reduced anti-dsDNA antibody levels by 45% and improved renal histopathology [1]
- Neuroinflammation Reduction: In a mouse model of experimental autoimmune encephalomyelitis (EAE), Edecesertib (20 mg/kg, BID) significantly decreased spinal cord inflammation and demyelination, with efficacy comparable to fingolimod (2.5 mg/kg) [1] - Safety in Non-Human Primates: In cynomolgus monkeys, Edecesertib (200 mg/kg, p.o.) for 7 days showed no drug-related adverse effects, and no QT interval prolongation was observed [1] |
| Enzyme Assay |
- IRAK4 Kinase Activity Assay: Recombinant IRAK4 kinase domain was incubated with ATP and a biotinylated peptide substrate in the presence of Edecesertib (0.01–1000 nM). Phosphorylation was detected via streptavidin-HRP, and IC₅₀ = 0.6 nM was determined [1]
- Kinase Selectivity Panel: Edecesertib (1000 nM) was tested against 72 kinases using a fluorescence polarization-based assay. Selectivity ratios were calculated by comparing IRAK4 IC₅₀ with other kinases’ IC₅₀ values [1] |
| Cell Assay |
- Human Whole Blood Assay: Heparinized human blood was treated with Edecesertib (0.1–1000 nM) and stimulated with LPS (1 μg/mL). TNF-α levels in plasma were measured by ELISA, yielding EC₅₀ = 124 nM [1]
- THP-1 Macrophage Assay: Cells (1×10⁶ cells/mL) were pretreated with Edecesertib (1–10 μM) for 1 hour, followed by LPS stimulation. Supernatants were analyzed for IL-6/IL-1β by ELISA, showing dose-dependent inhibition [1] |
| Animal Protocol |
- NZB/W F1 Mouse Model: Mice (8-week-old) received Edecesertib (30 mg/kg) dissolved in 0.5% CMC-Na via oral gavage daily for 28 days. Serum anti-dsDNA antibodies and renal histology were evaluated [1]
- EAE Rat Model: Rats were immunized with MOG35-55 peptide and treated with Edecesertib (20 mg/kg, BID, p.o.) starting on day 0. Clinical scores and spinal cord inflammation were assessed at day 28 [1] - Cynomolgus Monkey Toxicity Study: Animals received Edecesertib (50–200 mg/kg) in capsules daily for 7 days. Safety parameters included ECG monitoring, hematology, and clinical chemistry [1] |
| ADME/Pharmacokinetics |
Oral bioavailability: In rats, the bioavailability of Edecesertib was 34% after oral administration (10 mg/kg), with a peak plasma concentration (Cmax) of 1.2 μg/mL at 1.5 hours [1] - Half-life: The terminal half-life (t₁/₂) in rat plasma was 3.2 hours, and in cynomolgus monkeys it was 4.8 hours [1] - Tissue distribution: The highest drug concentrations were found in the kidneys (5.8 μg/g) and spleen (4.1 μg/g) of rats 2 hours after administration [1] - Plasma protein binding: Moderate binding was observed in human plasma (free fraction = 4.4%) [1]
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| Toxicity/Toxicokinetics |
Preclinical safety: No drug-related deaths or organ toxicity were observed in rats (14 days, 300 mg/kg) and cynomolgus monkeys (7 days, 200 mg/kg). No QT interval prolongation was detected in telemetry-monitored dogs [1]
-hERG safety: Edecesertib IC₅₀ > 30 μM in hERG channel assays, indicating a low risk of arrhythmias [1] -Human Phase I tolerability: In healthy subjects, single escalation doses up to 400 mg and multiple doses of 200 mg once daily were well tolerated without serious adverse events [4] |
| References | |
| Additional Infomation |
Mechanism of action: Edecesertib binds to the ATP-binding site of IRAK4, blocking the formation of the Myddosome complex and the activation of downstream NF-κB/p38 MAPK, thereby inhibiting the production of pro-inflammatory cytokines [1,2] - Structural optimization: The compound was developed by modifying the pyridine core and R1/R3 substituents to eliminate hERG toxicity while maintaining inhibitory activity against IRAK4. Key modifications include cyanomethyl substitution and pyrrolopyridazine ring [1,2] - Clinical development: Currently undergoing Phase II clinical trials for the treatment of cutaneous lupus erythematosus (CLE) and rheumatoid arthritis (RA) [1,2] - FDA designation: Fast Track designation for systemic lupus erythematosus (SLE) is expected in 2023 [1]
|
| Molecular Formula |
C22H22FN7O2
|
|---|---|
| Molecular Weight |
435.454186916351
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| Exact Mass |
435.181
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| Elemental Analysis |
C, 60.68; H, 5.09; F, 4.36; N, 22.52; O, 7.35
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| CAS # |
2408839-73-4
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| PubChem CID |
147817927
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| Appearance |
Light yellow to yellow solid powder
|
| LogP |
1.8
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
32
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| Complexity |
775
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| Defined Atom Stereocenter Count |
2
|
| SMILES |
C1=NC(C2N3C(=CC=2)C=C(C#N)C=N3)=CC(N[C@@H](C#N)C)=C1C(NC[C@@H](F)C(O)(C)C)=O
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| InChi Key |
HORBHQPSWJRDSV-ZUOKHONESA-N
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| InChi Code |
InChI=1S/C22H22FN7O2/c1-13(8-24)29-17-7-18(19-5-4-15-6-14(9-25)10-28-30(15)19)26-11-16(17)21(31)27-12-20(23)22(2,3)32/h4-7,10-11,13,20,32H,12H2,1-3H3,(H,26,29)(H,27,31)/t13-,20-/m1/s1
|
| Chemical Name |
4-[[(1R)-1-cyanoethyl]amino]-6-(3-cyanopyrrolo[1,2-b]pyridazin-7-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide
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| Synonyms |
Edecesertib; 3NUJ7N1277; 4-[[(1R)-1-cyanoethyl]amino]-6-(3-cyanopyrrolo[1,2-b]pyridazin-7-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide; 4-(((1R)-1-cyanoethyl)amino)-6-(3-cyanopyrrolo(1,2-b)pyridazin-7-yl)-N-((2R)-2-fluoro-3-hydroxy-3-methylbutyl)pyridine-3-carboxamide; 2408839-73-4; Edecesertib [INN]; UNII-3NUJ7N1277; 3-Pyridinecarboxamide, 4-(((1R)-1-cyanoethyl)amino)-6-(3-cyanopyrrolo(1,2-b)pyridazin-7-yl)-N-((2R)-2-fluoro-3-hydroxy-3-methylbutyl)-;
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 : ~100 mg/mL (~229.65 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.74 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.74 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2965 mL | 11.4824 mL | 22.9647 mL | |
| 5 mM | 0.4593 mL | 2.2965 mL | 4.5929 mL | |
| 10 mM | 0.2296 mL | 1.1482 mL | 2.2965 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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