Pexmetinib (ARRY-614) is a potent, orally bioavailable, dual p38 MAPK/Tie-2 inhibitor with IC50 of 4 nM/18 nM in a HEK-293 cell line. Phase 1.
Storage Temp
Store at -20°C
Shipped In
Ice chest + Ice pads
Grade
Moligand™
Action Type
INHIBITOR
Mechanism of action
Tyrosine-protein kinase TIE-2 inhibitor
Product Description
Information
Pexmetinib (ARRY-614) Pexmetinib (ARRY-614) is a potent, orally bioavailable, dual p38 MAPK/Tie-2 inhibitor with IC50 of 4 nM/18 nM in a HEK-293 cell line. Phase 1.
Targets
p38 MAPK ; Tie-2
In vitro
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.
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.
1.Bachegowda L, Gligich O, Mantzaris I, Schinke C, Wyville D, Carrillo T, Braunschweig I, Steidl U, Verma A. (2013) Signal transduction inhibitors in treatment of myelodysplastic syndromes.. J Hematol Oncol, 6 (3):(50). [PMID:23841999]
2.Garcia-Manero G, Khoury HJ, Jabbour E, Lancet J, Winski SL, Cable L, Rush S, Maloney L, Hogeland G, Ptaszynski M et al.. (2015) A phase I study of oral ARRY-614, a p38 MAPK/Tie2 dual inhibitor, in patients with low or intermediate-1 risk myelodysplastic syndromes.. Clin Cancer Res, 21 (5):(985-94). [PMID:25480830]
3.Gañán-Gómez I, Bohannan ZS, Garcia-Manero G. (2015) p38 MAPK in MDS.. Aging (Albany NY), 7 (6):(346-7). [PMID:26081220]
4.Bachegowda L, Morrone K, Winski SL, Mantzaris I, Bartenstein M, Ramachandra N, Giricz O, Sukrithan V, Nwankwo G, Shahnaz S et al.. (2016) Pexmetinib: A Novel Dual Inhibitor of Tie2 and p38 MAPK with Efficacy in Preclinical Models of Myelodysplastic Syndromes and Acute Myeloid Leukemia.. Cancer Res, 76 (16):(4841-4849). [PMID:27287719]
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