BTK inhibitor 17

Research use only, not for human use.

BTK inhibitor 17 is a potent irreversible BTK inhibitor (IC50 = 2.1 nM). BTK inhibitor 17 can be used in rheumatoid arthritis studies.

BTK inhibitor 17 is a potent irreversible BTK inhibitor (IC50 = 2.1 nM). BTK inhibitor 17 can be used in rheumatoid arthritis studies.(In Vitro):BTK inhibitor 17 exhibited high potency against BTK kinase and acceptable PK profile. BTK inhibitor 17 could covalently bind to Cys481 and formed an HB network with gatekeeper Thr474, hinge key residues Met477 and Glu475.(In Vivo):BTK inhibitor 17 demonstrated significant in vivo efficacy in a mouse-collagen-induced arthritis (CIA) model. BTK inhibitor 17 shows >95% plasma protein binding across three species of human, rat, and mouse. After an intravenous injection, the half-life (rat, 0.32 h; mice, 0.42 h), clearance (rat, 54.6 mL/min/kg; mice, 31.3 mL/min/kg), volume of distribution (rat, 1.55 L/kg; mice, 0.82 L/kg), and AUC exposure (rat, 604 ng.h/mL; mice, 576 ng.h/mL) are observed in two species. After oral administration, BTK inhibitor 17 exhibits higher Cmax (rat, 466 ng/mL; mice, 252 ng/mL) and plasma exposure (rat, 642 ng.h/mL; mice, 128 ng.h/mL) with a favorable oral bioavailability (rat, 23.7%; mice, 11.2%). In male Balb/C mice injected with collagen, BTK inhibitor 17 inhibited the significant progression of the disease and exhibited a clear dose-dependent reduction per paw clinical scores.

BTK inhibitor 17 (compound 8) could covalently bind to Cys481 and formed an HB network with hinge key residues Met477, Glu475, and gatekeeper Thr474.

BTK inhibitor 17 (compound 8; 3-10 mg/kg; oral gavage; daily; for 28 days) treatment inhibits the significant progression of the disease and exhibits a clear dose-dependent reduction per paw clinical scores, and no significant body weight loss is observed for all different dosages. BTK inhibitor 17 (compound 8) shows >95% plasma protein binding across three species of human, rat, and mouse. After an intravenous injection, the half-life (rat, 0.32 h; mice, 0.42 h), clearance (rat, 54.6 mL/min/kg; mice, 31.3 mL/min/kg), volume of distribution (rat, 1.55 L/kg; mice, 0.82 L/kg), and AUC exposure (rat, 604 ng.h/mL; mice, 576 ng.h/mL) are observed in two species. After oral administration, BTK inhibitor 17 exhibits higher Cmax (rat, 466 ng/mL; mice, 252 ng/mL) and plasma exposure (rat, 642 ng.h/mL; mice, 128 ng.h/mL) with a favorable oral bioavailability (rat, 23.7%; mice, 11.2%). Animal Model:Male Balb/C mice injected with collagenDosage:3 mg/kg or 10 mg/kg Administration:Oral gavage; daily; for 28 days Result:Inhibited the significant progression of the disease and exhibited a clear dose-dependent reduction per paw clinical scores.

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Tyrosine Kinase

BTK

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1858206-76-4

456.5

C25H24N6O3

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (219.06 mM)

C=CC(N(CCC1)C[C@@H]1n(c1c2C(N)=NNC1=O)nc2-c(cc1)ccc1Oc1ccccc1)=O

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(-20℃)

With Ice Pack

≥ 2 years