Pexmetinib hydrochloride

Pexmetinib hydrochloride potently inhibits Tie-2, p38 MAPK α and p38 MAPK β, and is a type 2 kinase that binds to the "DFG-out" conformation of these kinases^[1].
Pexmetinib (2 h) hydrochloride inhibits doxycycline (HY-N0565)-induced phosphorylation of Tie-2 and p38 MAPK in HEK-Tie2 cells, as well as anisomycin (HY-18982)-stimulated phosphorylation of Tie-2 and p38 MAPK in HUVECs, while also suppressing their respective downstream mediators pHsp27 and pAkt^[1].
Pexmetinib (0.1 μM; 14 days) hydrochloride reverses TNF-α-mediated myelosuppression of erythroid (BFU-E) and myeloid (CFU-GM) colony formation in primary CD34⁺ hematopoietic stem cells from healthy humans^[1].
Pexmetinib (for 14-17 days) hydrochloride stimulates hematopoietic differentiation and increases the number and size of erythroid (BFU-E) and myeloid (CFU-GM) colonies in primary monocytes from patients with myelodysplastic syndrome (MDS)^[1].
Pexmetinib (0.1-0.4 μM; 5 days) hydrochloride inhibits RANKL-induced osteoclast formation in primary bone marrow macrophages in a concentration-dependent manner^[2].
Pexmetinib (0.1-0.4 μM; 3 days) hydrochloride reduces the bone resorptive activity of mature osteoclasts differentiated from primary bone marrow macrophages in a dose-dependent manner, with an approximately 88% reduction in bone resorptive activity following treatment with 0.4 μM for 3 days^[2].
Pexmetinib (0.1-0.4 μM; 5 days) hydrochloride inhibits the expression of osteoclast-specific genes in RANKL-induced primary bone marrow macrophages^[2].
Pexmetinib (0.4 μM; 3-5 days) hydrochloride inhibits RANKL-induced NFATc1 and CTSK protein expression in primary bone marrow macrophages after 3 and 5 days of incubation^[2].
Pexmetinib (0.4 μM; 2 h pretreatment, followed by RANKL stimulation for 0-60 min) hydrochloride specifically inhibits RANKL-induced p38 phosphorylation and subsequent STAT3 activation in primary bone marrow macrophages^[2].
Pexmetinib (0.4 μM; 48 h) hydrochloride reduces the binding of STAT3 to the NFATc1 promoter in RAW264.7 cells stimulated with RANKL for 48 h^[2].
Pexmetinib (pre-incubated for 1 h; stimulated for 16 h) hydrochloride inhibits LPS (HY-D1056)-induced TNFα production (a functional readout of p38 inhibition), with an IC₅₀ value of 313 nM in whole blood and 4.5 nM in peripheral blood mononuclear cells (PBMCs); after correction for protein binding, the predicted IC₅₀ values are 2282 nM for pTie2 and 172 nM for p-p38 in plasma^[1].
Pexmetinib hydrochloride completely abrogates TNF-α-induced p38 MAPK activation, and inhibits the activation of downstream effectors MAPKAPK2 and EIF4E in KG1 acute myeloid leukemia (AML) cells^[1].
Pexmetinib hydrochloride potently inhibits the proliferation of KG1 and CMK acute myeloid leukemia (AML) cell lines in vitro^[1].
Pexmetinib (0-64 μM; 48-96 h) hydrochloride reduces the viability of human MDA-MB-231 breast cancer cells in a concentration-dependent manner, with an IC₅₀ of 17.43 μM at 96 h^[2].
Pexmetinib (4 μM; 0-24 h) hydrochloride inhibits the phosphorylation of p38 and STAT3 in human MDA-MB-231 breast cancer cells^[2].
Pexmetinib (1-4 μM) hydrochloride inhibits the migration and invasion of human MDA-MB-231 breast cancer cells in a concentration-dependent manner^[2].
Pexmetinib (1-4 μM; 24 h) hydrochloride inhibits the gene and protein expression of MMP-2 and MMP-9 in human MDA-MB-231 breast cancer cells^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.