Poseltinib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Poseltinib (HM-71224, LY-3337641) 是一种有效的选择性 Btk 共价抑制剂，IC50 为 1.95 nM。

Poseltinib (HM-71224, LY-3337641) is a potent and selective, covalent inhibitor of Btk with IC50 of 1.95 nM; also inhibits BMX, TEC, TXK, EGFR in biochemical sense (IC50=0.3-2.5 nM); effectively inhibits the phosphorylation of Btk and PLCγ2, and inhibits expression of CD40, CD69, and CD86 by activated primary human B cells with IC50 of 4.2, 4.2, and 7.7 nM, respectively; inhibited the production of TNF-α, IL-6, and IL-1β by human monocytes, and osteoclast formation by human monocytes; ameliorates arthritis in a mouse model.Rheumatoid Arthritis Phase 1 Clinical.

Western Blot Analysis Cell Line: B cells Concentration:0.1-100 nM Incubation Time:30 min Result:Blocked both autophosphorylation of BTK and phosphorylation of PLCγ2 with IC50 values of less than 10 nM.Decreased the production of both TNF-α and IL-6 in a dose-dependent manner.

Animal Model:MRL/lpr mice and NZB/W F1 mice modelsDosage:3-30 mg/kg Administration:p.o Result:Decreased the spleen weights and prevented skin lesion progression.Ameliorated renal injury and inflammation and improved the survival rate.Animal Model:Collagen-induced arthritis (CIA) mouse model Dosage:1-30 mg/kg Administration:p.o Result:Reduced the serum IL-6, circulating anti-collagen antibodies and total IgG levels.Reduced erosive bone changes and prevented bone loss.

HM-71224 | LY-3337641

Tyrosine Kinase

BTK

BTK

Inflammation/Immunology

Rheumatoid Arthritis

1353552-97-2

470.533

C26H26N6O3

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (212.53 mM)

C=CC(NC1=CC=CC(OC2=C(OC=C3)C3=NC(NC4=CC=C(N5CCN(C)CC5)C=C4)=N2)=C1)=O

2-Propenamide, N-[3-[[2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]furo[3,2-d]pyrimidin-4-yl]oxy]phenyl]-

(-20℃)

With Ice Pack

≥ 2 years