product name Cerdulatinib HCl salt
Description: Cerdulatinib, also known as PRT2070 and PRT062070, 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. It also inhibits 19 other tested kinases with IC50 less than 200 nM. It is currently being studied in patients with genetically-defined hematologic cancers, as well as for patients who have failed therapy due to relapse or acquired mutations.
References: J Pharmacol Exp Ther. 2014 Dec;351(3):538-48.
482 (HCl salt)
Formula
C20H28ClN7O3S
CAS No.
1369761-01-2 (HCl salt); 1198300-79-6 (free base)
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 43 mg/mL (89.2 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
5% DMSO+corn oil: 3mg/mL
Synonyms
PRT062070, PRT2070
other peoduct :
| In Vitro |
In vitro activity: 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. Kinase Assay: 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 Assay: 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. |
|---|---|
| In Vivo | 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. |
| Animal model | Rat collagen-induced arthritis model |
| Formulation & Dosage | Dissolved in 0.5% methylcellulose in water; 5 mg/kg; Oral administration |
| References | J Pharmacol Exp Ther. 2014 Dec;351(3):538-48. |
