| Identification | Back Directory | [Name]
2-Pyridinecarboxamide, N-[6-(1-hydroxy-1-methylethyl)-2-[2-(methylsulfonyl)ethyl]-2H-indazol-5-yl]-6-(trifluoromethyl)- | [CAS]
1931994-81-8 | [Synonyms]
BAY-1834845
Zabedosertib
N-(6-(2-Hydroxypropan-2-yl)-2-(2-(methylsulfonyl)ethyl)-2H-indazol-5-yl)-6-(trifluoromethyl)picolinamide
N-[6-(1-hydroxy-1-methyl-ethyl)-2-(2-methylsulfonylethyl)indazol-5-yl]-6-(trifluoromethyl)pyridine-2-carboxamide
2-Pyridinecarboxamide, N-[6-(1-hydroxy-1-methylethyl)-2-[2-(methylsulfonyl)ethyl]-2H-indazol-5-yl]-6-(trifluoromethyl)- | [Molecular Formula]
C20H21F3N4O4S | [MDL Number]
MFCD32900903 | [MOL File]
1931994-81-8.mol | [Molecular Weight]
470.47 |
| Chemical Properties | Back Directory | [Boiling point ]
620.7±55.0 °C(Predicted) | [density ]
1.44±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 125 mg/mL (265.69 mM; ultrasonic and warming and heat to 60°C) | [form ]
Solid | [pka]
11.53±0.43(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
Zabedosertib (BAY 1834845) is a selective, orally active IRAK4 inhibitor with immunomodulatory potential, IC50 is 3.55 nM. IRAK4 is a protein kinase involved in signaling innate immune responses from Toll-like receptors[1]. Zabedosertib exhibits anti-inflammatory property against IL-β, LPS (HY-D1056) and Imiquimod (HY-B1080) induced inflammation[2]. | [in vivo]
Zabedosertib (150 mg/kg, p.o., twice) prevents lung injury and reduces inflammation in LPS induced ARDS in BALB/c mice[2].
Zabedosertib inhibits IL-β(p.o., 40-80 mg/kg, once), LPS (p.o., 10-40 mg/kg, once) and Imiquimod (p.o., 15-150 mg/kg, twice daily for 7 days) induced inflammation[3].
Zabedosertib has a Pharmacokinetic profile in rats[3]:
Pharmacokinetic Analysis of Zabedosertib in rats[1]
| species | Doseiv (mg/kg) | AUCnorm,iv (kg·h/L) | CLblood (L/h/kg) | Vss (L/kg) | T1/2,iv (h) | Dosepo(mg/kg) | AUCnorm,po (kg·h/L)) | Cmax,norm (kg/L) | Tmax (h) | F (%) | | rat | 0.5 | 5.6 | 0.24 | 0.92 | 4.2 | 2.0 | 5.3 | 0.55 | 4.0 | 94 | | dog | 0.5 | 15 | 0.088 | 1.6 | 17 | 1.0 | 15 | 0.57 | 2.0 | 104 |
| Animal Model: | LPS induced ARDS in BLAB/c mice[2] | | Dosage: | 150 mg/kg | | Administration: | p.o., twice (30 min before and 6 h after LPS-injection or 4 h and 12 h after LPS-injection) | | Result: | Decreased inflammatory cells infiltration.
Combination of Zabedosertib and DEX ( HY-14648) decreased T-cells, monocytes and macrophages.
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| Animal Model: | BALB/c mice[3] | | Dosage: | IL-β:40-80 mg/kg, LPS: 10-40 mg/kg, Imiquimod: 15-150 mg/kg | | Administration: | oral gavage, IL-β: once, LPS: once, Imiquimod: twice daily for 7 days | | Result: | Inhibited IL-β, LPS induced inflammation in a dose-dependent manner. Inhibited Imiquimod induced inflammation. |
| [IC 50]
IRAK4: 3.55 nM (IC50) | [storage]
Store at -20°C | [References]
[1] Bothe, Ulrich; Siebenreicher, Holger; Schmidt, Nicole; Nubbemeyer, Reinhard; Boemer, Ulf; Guenther, Judith; Steuber, Holger; Lange, Martin; Stegmann, Christian; Sutter, Andreas; et al.New substituted indazoles, methods for the production thereof, pharmaceutical preparations that contain said new substituted indazoles, and use of said new substituted indazoles to produce drugs.WO2016083433A1
[2] Li Q, et al., Oral IRAK4 inhibitor BAY-1834845 prevents acute respiratory distress syndrome. Biomed Pharmacother. 2022 Sep;153:113459. DOI:10.1016/j.biopha.2022.113459
[3] Bothe U, et al., Discovery of IRAK4 Inhibitors BAY1834845 (Zabedosertib) and BAY1830839. J Med Chem. 2024 Jan 25;67(2):1225-1242. DOI:10.1021/acs.jmedchem.3c01714 |
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