syk in 3

Syk-IN-3 is a Syk inhibitor with potential anti-inflammatory and anticancer activity and can be used to study immune dysregulation.

PRT-060318 (PRT318) dihydrochloride is a potent, highly selective tyrosine kinase Syk inhibitor with an IC50 of 3 nM, and is orally bioavailable. It inhibits the activation and migration of B cells in chronic lymphocytic leukemia (CLL) and induces apoptosis. Additionally, PRT-060318 dihydrochloride offers potential therapeutic applications by preventing heparin-induced thrombocytopenia and thrombosis in transgenic mouse models, making it useful in studies of chronic lymphocytic leukemia and thrombosis.

Type-II-IN-1 (Compound 3) is a Type II spleen tyrosine kinase (Syk) inhibitor with an IC50 value of 2.1 nM. Type-II-IN-1 binds to the DFG-out conformation of Syk, and it may be applied in immunology studies, including research on asthma.

Midostaurin (PKC412) is a multi-targeted tyrosine kinase inhibitor with antitumor activity, exhibiting IC50 values ranging from 22 to 500 nM against PKCα/β/γ, Syk, Flk-1, Akt, PKA, c-Kit, c-Fgr, c-Src, FLT3, PDFRβ, and VEGFR1/2. Midostaurin is indicated for the treatment of acute myeloid leukemia (AML) and systemic mastocytosis (SM).

1. Glaucocalyxin A (Leukamenin F)-SBE-β-CD could be useful with a better solubility and sustained function in drug delivery. 2. Glaucocalyxin A activates caspase-3, decreases BAD phosphorylation, and reduces the expression of X-linked inhibitor of apoptosis protein. 3. Glaucocalyxin A inhibits Akt phosphorylation, suppresses proliferation, and promotes apoptosis in a dose-dependent manner, but not in normal glial cells. 4. Glaucocalyxin A inhibits collagen-stimulated tyrosine phosphorylation of Syk, LAT, and phospholipase Cγ2, the signaling events in collagen receptor GPⅥ pathway. 5. Glaucocalyxin A could potentially be developed as an antiplatelet and antithrombotic agent, can inhibit platelet p-selectin secretion and integrin activation by convulxin, is a GPVI selective ligand.

The impact of spleen tyrosine kinase (Syk) signaling might be prominent in lupus because (i) Syk is a shared downstream signaling molecule among circulating immune complex, LPS, and (1→3)-β-D-glucan (BG), and (ii) all of these factors are detectable in the serum of Fc gamma receptor IIb-deficient (FcgRIIb-/-) mice with sepsis. Syk inhibition downregulated several inflammatory pathways in FcgRIIb-/- macrophages activated with BG + LPS suggesting the potential anti-inflammatory impact of Syk inhibitors in lupus. Indeed, administration of a Syk inhibitor prior to cecal ligation and puncture (CLP) sepsis in FcgRIIb-/- mice reduced baseline lupus-induced proinflammatory cytokines and attenuated sepsis severity as evaluated by mortality, organ injury, serum LPS, and post-sepsis serum cytokines.