product name Pexmetinib (ARRY-614)
Description: Pexmetinib, also known as ARRY-614, is a potent, orally bioavailable, dual inhibitor of p38 and Tie2 kinases with IC50 of 4 nM/18 nM in a HEK-293 cell line. Pexmetinib has potential antineoplastic, anti-inflammatory and antiangiogenic activities. Pexmetinib binds to and inhibits the activities of p38 and Tie2 kinases, which may inhibit the production of proinflammatory cytokines and may decrease tumor angiogenesis and tumor cell growth and survival.
References: Clin Cancer Res. 2015 Mar 1;21(5):985-94.
556.63
Formula
C31H33FN6O3
CAS No.
945614-12-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (179.6 mM)
Water: <1 mg/mL
Ethanol:
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: In HeLa cells, Pexmetinib inhibits phospho-HSP27 with IC50 of 2 nM. In isolated PBMCs and human whole blood cells, Pexmetinib inhibits LPS-Induced TNFα with IC50 of 4.5 nM and 313 nM, respectively. Kinase Assay: Pexmetinib (ARRY-614) is a potent inhibitor of cytokine synthesis, via the dual inhibition of p38 mitogen-activated protein kinase (MAPK), and Tie2/Tek receptor tyrosine kinase. The in vitro IC50 values of ARR Y-614 for both Tie2 and p38 mitogen-activated protein kinase are 1000 ng/mL and 100 ng/mL, respectively. Cell Assay: In primary human bone marrow stromal cells, ARRY-614 inhibited basal cytokines with an IC50 value ranging from 50-100 nM. |
|---|---|
| In Vivo | In male Swiss Webster mice, Pexmetinib (30 mg/kg, p.o.) inhibits the production of the proinfl ammatory cytokines TNFα and IL6 in response to lipopolysaccharide (LPS) or staphyloccus enterotoxin A. In established RPMI 8226 xenografts, ARRY-614 (25 mg/kg, p.o.) inhibits tumor growth and shows additive activity when combines with thalidomide. In ovarian carcinoma A2780 xenografts, ARRY-614 (30 mg/kg, p.o.) also shows additive tumor growth inhibition activity when combines with Taxol. |
| Animal model | RPMI 8226 xenografts |
| Formulation & Dosage | 25 mg/kg; p.o. |
| References | Clin Cancer Res. 2015 Mar 1;21(5):985-94. |
