WC36 is a potent, specific inhibitor of Syk-cSH2 with IC50 of 40 nM, inhibits Syk-cSH2-PIP3 binding, specifically and potently suppresses oncogenic activities of Syk in AML cells.
WC36 potently blocks BCR-mediated activation of Syk in B cells, effectively suppresses phosphorylation of all BCR signaling proteins.
WC36 does not inhibit binding of ZAP-70-cSH2 to PIP3-containing vesicles, showing selectivity for Syk-cSH2 over ZAP-70-cSH2.
WC36 (5 uM) potently suppressed the phosphorylation and activation of Syk, ERK1/2 and STAT3/5 in entospletinib-resistant MV4-11 cells, but not 5 μM entospletinib.
WC36 potently inhibited proliferation of entospletinib-resistant MV4-11 cells.
WC36 suppressed HL-60 and patient-derived AML cells, while entospletinib was ineffective, WC36 potently inhibited phosphorylation of Syk, ERK1/2 and STAT3/5 in AML cells.
WC36 blocks not only the Syk kinase activity, but also its noncatalytic scaffolding function that is linked to drug resistance.