Vecabrutinib

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

Vecabrutinib (SNS-062) 是一种有效、可逆、非共价 BTK 抑制剂，对于 WT BTK 和 C481S BTK 的 IC50 分别为 2.9 和 4.4 nM。

Vecabrutinib (SNS-062) is a potent, reversible, non-covalent BTK inhibitor with IC50 of 2.9 and 4.4 nM for WT BTK and C481S BTK, respectively;Binds to Tec kinase family members BTK (Kd=0.3 nM) and ITK (Kd=2.2 nM), but not bind EGFR, active in vitro in cells with the C481S mutation;Inhibits pBTK in human whole blood with IC50 of 50 nM, demonstrates favorable pharmacokinetic properties, shows potential for overcoming the ibrutinib resistance due to C481S mutantion in BTK.Blood Cancer Phase 2 Clinical.

Vecabrutinib inhibits pBTK in human whole blood with an average IC50 of 50 nM. Vecabrutinib inhibits WT and C481S BTK with similar IC50s (pBTK IC50s: WT BTK 2.9 nM, C481S BTK 4.4 nM). In a recombinant kinase assay, IC50s of Vecabrutinib against WT BTK and C481S BTK are 4.6 nM and 1.1 nM. Vecabrutinib retains activity against the mutated BTK variant. Vecabrutinib is six times more potent than PCI-32765 and greater than 640 times more potent than acalabrutinib against C481S BTK. Vecabrutinib demonstrates dose-dependent inhibition of BTK in primary patient CLL cells comparable to PCI-32765 via immunoblot for BTK phosphorylation. Vecabrutinib decreases viability of primary CLL cells in the presence of HS5 stromal protection by 5.5%.

Vecabrutinib has good oral bioavailability in rat and dog (%F ≥ 40%) and a terminal half-life of 5 to 6 hours. Vecabrutinib is well tolerated with continuous drug levels and at exposures much greater than those achieved for PCI-32765.

SNS 062 | SNS062 | SNS-062

Tyrosine Kinase

BTK

BTK

Cancer

Blood cancer

1510829-06-7

529.925

C22H24ClF4N7O2

>98% (HPLC)

DMSO : 125 mg/mL. 235.88 mM

O=C1N([C@H]2CN(C3=NC=NC(N)=C3F)CC[C@@H]2C(N)=O)CCC[C@H]1NC4=CC(C(F)(F)F)=CC(Cl)=C4

(3R,3'R,4'S)-1'-(6-amino-5-fluoropyrimidin-4-yl)-3-[3-chloro-5-(trifluoromethyl)anilino]-2-oxo[1,3'-bipiperidine]-4'-carboxamide

(-20℃)

With Ice Pack

≥ 2 years