RO9021 is an orally bioavailable, novel ATP-competitive SYK inhibitor [average IC50: 5.6 nM].

Syk:5.6 nM

RO9021 effectively inhibits the anti-IgM induced phosphorylation of key signaling proteins including BTK, PLCγ2, AKT, and ERK, thereby demonstrating its capacity to block SYK kinase activity and consequently attenuate the B-cell receptor (BCR) downstream signaling cascade. This compound selectively targets B-cell receptor signaling, underscored by its role as a highly selective inhibitor of SYK. Its selectivity is evidenced by low S-scores of 0.003 for S(99) and 0.015 for S(90), indicating that among 392 kinases tested, SYK is the sole kinase significantly competed by RO9021 with 99% effectiveness. Moreover, RO9021 exhibits comparable inhibitory potency (IC50=22.8±1.7 nM) in assays measuring FcεR-mediated mast cell activation and degranulation, highlighting its broad potential in modulating immune responses [1].