Syk Inhibitor

GSK143 dihydrochloride is an orally active and highly selective spleen tyrosine kinase (SYK) inhibitor with a pIC₅₀ of 7.5. GSK143 dihydrochloride inhibits phosphorylated Erk (pErk: pIC₅₀=7.1). GSK143 dihydrochloride reduces inflammation and prevents recruitment of immune cells in the intestinal muscularis in mice.

Fostamatinib (R788) disodium hexahydrate is the oral proagent of the active compound R406. R406 is an orally available and competitive Syk/FLT3 inhibitor with a K_i of 30 nM and an IC₅₀ of 41 nM. R406 also inhibits Lyn (IC₅₀=63 nM) and Lck (IC₅₀=37 nM).

Syk-IN-4 is a potent, selective and orally bioavailable SYK inhibitor with an IC₅₀ of 0.31 nM. SYK has emerged as a potential target for autoimmunity and hematological cancers.

R112 is a fast and reversible inhibitor of spleen tyrosine kinase (Syk) kinase. R112 inhibits Syk kinase activity with an IC₅₀ value of 226 nM and a Ki value of 96 nM. R112 inhibits IgE-FcεRI signaling pathway. R112 can be used for the research of allergic rhinitis.

SRX3207 is an orally active and first-in-class dual Syk/PI3K inhibitor, with IC₅₀ values of 10.7 nM and 861 nM for Syk and PI3Kα, respectively. SRX3207 relieves tumor immunosuppression.

Cevidoplenib (SKI-O-703) is an orally available inhibitor of spleen tyrosine kinase (Syk), with potential anti-inflammatory and immunomodulating activities. Cevidoplenib is also the mesylate form of SKI-O-592. Cevidoplenib and SKI-O-592 inhibits BCR-mediated survival, proliferation, and differentiation of B cells. And SKI-O-592 potently inhibits multiple kinases with IC₅₀s of 6.2 nM (Syk), 1.859 μM (Jak2), 5.807 μM (Jak3), 0.412 μM (RET), 0.687 μM (KOR), 1.783 μM (FLT3), 16.96 μM (FGFR1), 5.662 μM (FGFR3), and 0.709 μM (Pyk2), respectively.

Chemerin15 is an anti-inflammatory peptide derived from Chemerin. Chemerin15 binds to ChemR23. Chemerin15 inhibits TNFα-induced activation of Syk, ERK and Src kinases. Chemerin15 increases the expression of p-p38 mRNA and protein. Chemerin15 mediates phagocytosis, resolution of inflammation, CD62L shedding and downregulation of PSGL-1 expression in macrophages and microglia. Chemerin15 inhibits neutrophil-mediated vascular inflammation and myocardial ischemia-reperfusion injury via ChemR23. Chemerin15 enhances microglial phagocytosis, thereby alleviating cerebral ischemia-reperfusion injury.

RO9021 is an orally bioavailable, novel ATP-competitive inhibitor of SYK, with an average IC₅₀ of 5.6 nM.

Cerdulatinib hydrochloride (PRT062070) is a selective, oral active and reversible ATP-competitive inhibitor of dual SYK and JAK, with IC₅₀s of 32 nM, 0.5 nM, 12 nM, 6 nM and 8 nM for SYK and Tyk2, JAK1, 2, 3, respectively. Cerdulatinib hydrochloride could be used to research autoimmune disease and B-cell malignancies.

Lck inhibitor 2 is a bisanilino pyrimidine-derived tyrosine kinase inhibitor targeting LCK, BTK, LYN, SYK and TXK, with a K_d value of 10 nM against TXK.

OXSI-2 is a bioavailable, cell-permeable Syk inhibitor with an EC₅₀ of 313 nM and an IC₅₀ of 14 nM.

Lanraplenib succinate (GS-9876 succinate) is a highly selective and orally active SYK inhibitor (IC₅₀=9.5 nM) in development for the treatment of inflammatory diseases. Lanraplenib succinate (GS-9876 succinate) inhibits SYK activity in platelets via the glycoprotein VI (GPVI) receptor without prolonging bleeding time (BT) in monkeys or humans.

PRT062607 (P505-15) acetate is an orally available Syk inhibitor (IC₅₀: 1 nM) that inhibits inflammation and induction Apoptosis. PRT062607 acetate exerts potent antitumor activity in tumor xenograft mouse models..

UBX-382 is an orally active BTK PROTAC degrader with a DC₅₀ of 4.56 nM. UBX-382 inhibits B-cell receptor signaling by targeting BTK. UBX-382 shows superior degradation activity for wild-type and mutant BTK proteins. UBX-382 inhibits tumor growth in murine xenograft models harboring wild-type or C481S mutant BTK-expressing TMD-8 cells. UBX-382 can be used for the study of B-cell-related blood cancers.

GSK2646264 (Compound 44) is a potent and selective spleen tyrosine kinase (SYK) inhibitor with a pIC₅₀ of 7.1. GSK2646264 also inhibits other kinases with pIC₅₀ values of 5.4, 5.4, 5.3, 5, 4.5, <4.6 and <4.3 against LCK, LRRK2, GSK3β, JAK2, VEGFR2, Aurora B and Aurora A, respectively. GSK2646264 is penetrable into the epidermis and dermis of the skin.

Cevidoplenib is an orally available inhibitor of spleen tyrosine kinase (Syk), with potential anti-inflammatory and immunomodulating activities.

ER-27319 (maleate), an acridone derivative, is a potent and selective SKY inhibitor, and inhibits the tyrosine phosphorylation of SYK and its activity. ER-27319 (maleate) inhibits the release of antigen-induced allergic mediators from human and rat mast cells with an IC₅₀ of 10 μM and can be used for study in allergic diseases^{[1] [2]} .

MRL-SYKi is a chemical probe for gain-of-function variants of spleen tyrosine kinase (SYK). MRL-SYKi reduces the catalytic activity of SYK^S550Y, SYK^S550F and SYK^P342T, and downregulates the phosphorylation level of SYK^S550Y. MRL-SYKi serves as a template for developing NanoBRET tracers targeting SYK, enabling NanoBRET cellular target engagement assays for gain-of-function variants of SYK. MRL-SYKi is applicable to research related to inflammatory and immune diseases.

MTX-216 is a dual ATP-competitive inhibitor of PI3K and EGFR. MTX-216 cosuppresses Ki-67 and ribosomal S6 phosphorylation and induces apoptosis in NF1^LOF cells. MTX-216 suppresses the activity of SYK kinase, with an IC₅₀ of 281 nM. MTX-216 is used in the research of Melanoma.

Midostaurin-d₅ (PKC412-d₅) is a deuterium labeled Midostaurin. Midostaurin is a multi-targeted protein kinase inhibitor which inhibits PKCα/β/γ, Syk, Flk-1, Akt, PKA, c-Kit, c-Fgr, c-Src, FLT3, PDFRβ and VEGFR1/2 with IC₅₀s ranging from 22-500 nM.