For research use only. Not for therapeutic Use.
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].
Zabedosertib decreases inflammatory cytokines secretion (500 nM), such as IL-1, IFN-γ, TNF-α, and IL-17[2].
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
| Catalog Number | I038652 |
| CAS Number | 1931994-81-8 |
| Synonyms | N-[6-(2-hydroxypropan-2-yl)-2-(2-methylsulfonylethyl)indazol-5-yl]-6-(trifluoromethyl)pyridine-2-carboxamide |
| Molecular Formula | C20H21F3N4O4S |
| Purity | ≥95% |
| InChI | InChI=1S/C20H21F3N4O4S/c1-19(2,29)13-10-15-12(11-27(26-15)7-8-32(3,30)31)9-16(13)25-18(28)14-5-4-6-17(24-14)20(21,22)23/h4-6,9-11,29H,7-8H2,1-3H3,(H,25,28) |
| InChIKey | OQAMEEFUUFJZRS-UHFFFAOYSA-N |
| SMILES | CC(C)(C1=CC2=NN(C=C2C=C1NC(=O)C3=NC(=CC=C3)C(F)(F)F)CCS(=O)(=O)C)O |
| Reference | [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. [3]. Bothe U, et al., Discovery of IRAK4 Inhibitors BAY1834845 (Zabedosertib) and BAY1830839. J Med Chem. 2024 Jan 25;67(2):1225-1242. |
