Cerdulatinib hydrochloride 是一种选择性可逆，具有口服活性、 ATP 竞争性的Syk和JAK的双重抑制剂，抑制JAK1、2、3、Syk和Tyk2的IC50值分别为12、6、8、32 和 0.5 nM。它可用于研究自身免疫性疾病和B细胞恶性肿瘤。

Cerdulatinib (PRT-062070) is an oral active, multi-targeted tyrosine kinase inhibitor with IC50 of 12 nM/6 nM/8 nM/0.5 nM and 32 nM for JAK1/JAK2/JAK3/TYK2 and Syk, respectively. Also inhibits 19 other tested kinases with IC50 less than 200 nM.

In human whole blood from normal donors, Cerdulatinib affects BCR-mediated B-cell activation by dual inhibition of SYK and JAK. As a dual SYK/JAK inhibitor, Cerdulatinib significantly reduces cell viability in a subset of NHL cell lines, and induces apoptosis in BCR-signaling competent NHL cell lines. [1]

In a rat collagen-induced arthritis model, Cerdulatinib (5 mg/kg p.o.) significantly improves inflammatory infiltrate within the synovium and the integrity of the articular cartilage. In addition, Cerdulatinib also blocks BCR-induced B-cell activation and splenomegaly in mice. [1]

Purified Kinase Assays: Potency against purified SYK is determined by fluorescence resonance energy transfer. A broader panel of 270 purified kinases is surveyed in which PRT062070 is tested at a fixed concentration of 300 nM. [33P]-labeled substrate is measured after incubation of purified kinase with peptide substrate and [33P]ATP at the Km concentration for the kinase.

Cell lines (Ramos RA-1, Daudi, Toledo, SU-DHL4 and SU-DHL6) are cultured in RPMI media supplemented with 10% fetal bovine serum. Cells are treated with the indicated concentrations of PRT062070, the SYK-selective inhibitor PRT060318, the pan-JAK inhibitor 1, a 1:1 combination of PRT060318 and JAK inhibitor 1, or vehicle control (0.5% dimethylsulfoxide) for 72 hours. Cell viability assays are performed using CellTiter Glo in 384-well plates. Cells are seeded at a density of 5000 cells per well. (Only for Reference)

1369761-01-2

C20H28ClN7O3S

482.0

PRT2070;PRT062070;PRT2070 hydrochloride;PRT062070 hydrochloride;Cerdulatinib

Ethanol:<1 mgml
DMSO:40 mg/mL (83 mM)
H2O:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years