1
ERK5 inhibitor as key regulator in cancer treatment
Dana Farber
Small molecule
Oncology
Hit To Lead or Lead Optimization
Here,
we perform a targeted screen for kinase inhibitors, which modulate the
naive-primed pluripotent transition. We find that XMD compounds, which
selectively inhibit Erk5 kinase and BET bromodomain
family proteins, drive ESCs toward primed pluripotency.
Using
compound selectivity engineering and CRISPR/Cas9 genome editing, we reveal
distinct functions for Erk5 and Brd4 in pluripotency regulation. We show that
Erk5 signaling maintains ESCs
in
the naive state and suppresses progression toward primed pluripotency and neuroectoderm
differentiation.
PCT/US2015/014120