Spleen tyrosine kinase (Syk) is a 72 kDa non-receptor tyrosine kinase. Specifically, Syk is activated by binding the tandem SH2 domain to the immune receptor tyrosine activation motif (ITAM). Syk activates new targets, including CARD9/CARMA1-BCL10-MALT1 pathway and NLRP3 inflammasome. Besides, Syk is expressed in most hematopoietic cells. Syk has related to the innate recognition of C-type lectin to fungal and other microbial pathogens and tissue damage. Moreover, Syk is necessary to separate newly formed lymphatic vessels form the vascular system. Syk plays a key role in adaptive immune receptor signaling.

Furthermore, Syk is mainly relevant to the pathway dependent on ITAM (activation motif based on immune receptor tyrosine). Syk affects the early development and activation of B cells, degranulation of mast cells, phagocytosis of neutrophils and macrophages, and platelet activation. Meanwhile, Syk plays a central role in the development of allergic and autoimmune diseases and hematological malignancies such as B-cell lymphoma. Here, we will introduce a bioavailable, cell-permeable oxindole Syk inhibitor, OXSI-2.

OXSI-2 is an Oxindole Syk Inhibitor.

First of all, OXSI-2 is a Syk inhibitor with an EC50 of 313 nM and an IC50 of 14 nM. OXSI-2 with 2 μM completely inhibits Convulxin-induced platelet aggregation and shape change. Nonetheless, OXSI-2 also completely blocks GPVI-mediated dense granule release.

In the second place, OXSI-2 with 100 nM does not affect the platelet functional responses induced by Convulxin, and modest shape change is still evident at 1 μM. Adaptor protein LAT is a known substrate of Syk Kinase. Particularly, OXSI-2 completely inhibits LAT Y191 phosphorylation.

Last but not the least, OXSI-2 inhibits Syk mediated events in platelets. Obviously, OXSI-2 inhibits inflammasome assembly, caspase-1 activation, IL-1β processing and release, mitochondrial ROS generation, and pyroptotic cell death.

All in all, OXSI-2 is an oxindole Syk inhibitor.


Kamala Bhavaraju, et al. Eur J Pharmacol. 2008 Feb 12;580(3):285-90.