XMD8-92 is an ERK5 inhibitor (K
d = 80 nM) that less potently inhibits DCAMKL2, TNK1, and Plk4 (K
ds = 190, 890, and 600 nM, respectively) in a panel of 402 kinases.
1 It blocks ERK5 autophosphorylation, ERK5-mediated phosphorylation of promyelocytic leukemia protein (PML), and PML-dependent activation of p21.
1 XMD8-92 inhibits AP-1 transcriptional activity induced by MEK5-activated ERK5 but not that induced by Cdc37.
2 It inhibits bFGF-induced angiogenesis in a Matrigel
™ plug assay in mice and reduces tumor growth in a HeLa mouse xenograft model when administered at a dose of 50 mg/kg twice per day.
1 XMD8-92 also binds bromodomain-containing protein 4 (BRD4; K
d = 170 nM for BRD4 bromodomain 1).
3