Sovleplenib (HMPL-523) is a highly potent, orally available and selective SYK inhibitor with an IC50 of 25 nM. Anti-tumor activity. Sovleplenib can be used for the research of immune thrombocytopenia (ITP)[1].
GSK143 is an orally active and highly selective spleen tyrosine kinase (SYK) inhibitor with a pIC50 of 7.5. GSK143 inhibits phosphorylated Erk (pErk: pIC50=7.1)[1]. GSK143 reduces inflammation and prevents recruitment of immune cells in the intestinal muscularis in mice[2][3].
Syk Inhibitor II dihydrochloride dihydrate is a potent, high selective and ATP-competitive Syk inhibitor with an IC50 of 41 nM. Syk Inhibitor II dihydrochloride dihydrate inhibits 5-HT release from RBL-cells with an IC50 of 460 nM. Syk Inhibitor II dihydrochloride dihydrate shows less potent against other kinases and has anti-allergic effect[1].
Syk Kinase Peptide Substrate is a Syk kinase peptide substrate.
SYK/JAK-IN-1 is dual SYK/JAK inhibitor with IC50s of <5 nM for SYK and JAK2, respectively[1].
BAY 61-3606 (dihydrochloride) is a potent, ATP-competitive, reversible, and highly selective inhibitor of Syk tyrosine kinase (IC50=10 nM) with no inhibitory effect on Btk, Fyn, Itk, Lyn, and Src.
Syk-IN-8 (compound 19q) is a Syk inhibitor, with antiproliferative activity against multiple hematological tumour cells. Syk-IN-8 inhibits PLCγ2 phosphorylation, can be used for research in blood cancers[1].
ER-27319, an acridone derivative, is a potent and selective SYK inhibitor, and inhibits the tyrosine phosphorylation of SYK and its activity. ER-27319 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].
R112 is an ATP-competitive inhibitor of Syk kinase with a Ki of 96 nM. R112 inhibits Syk kinase activity with an IC50 of 226 nM. IC50 value: 226 nM [1]Target: Sykin vitro: R112 blocks leukotriene C4 production and all proinflammatory cytokines tested. Its onset of action was immediate, and the inhibition was reversible. R112 is able to completely inhibit all three IgE-induced mast cell functions: degranulation, lipid mediator production, and cytokine production. R112 potently, completely, and rapidly abrogated all mast cell activation cascades triggered by IgE receptor cross-linking.[1]
TAK-659 is a highly potent, selective, reversible and orally available inhibitor of spleen tyrosine kinase (SYK) and fms related tyrosine kinase 3 (FLT3), with an IC50 of 3.2 nM for SYK. TAK-659 induces cell death in tumor cells but not in nontumor cells, and with potential for the treatment of chronic lymphocytic leukemia (CLL)[1][2][3][4].
MNS is a potent and selective inhibitor of Src and Syk tyrosine kinases. target: src, syk. [1]IC50:29.3 (src), 2.5 uM (syk); [1]In vitro: no direct effects on protein kinase C, Ca2+ mobilization, Ca2+-dependent enzymes, PKC activation. MNS potently prevents GPIIb/IIIa activation and platelet aggregation without directly affecting other signaling pathways required for platelet activation. [1] [2] MNS is much more potent than genistein in inhibiting platelet aggregation and protein tyrosine phosphorylation. [2]
Fostamatinib (R788), a prodrug of the active metabolite R406, is a potent Syk inhibitor with IC50 of 41 nM.
RO9021 is an orally bioavailable, novel ATP-competitive inhibitor of SYK, with an average IC50 of 5.6 nM.
R406 is a potent Syk inhibitor with IC50 of 41 nM, strongly inhibits Syk but not Lyn, 5-fold less potent to Flt3. IC50 value: 41 nM [1]Target: Syk in vitro: R406 is a potent inhibitor of immunoglobulin E (IgE)- and IgG-mediated activation of Fc receptor signaling. R406 inhibits the anti-IgE-induced production and release of LTC4 and cytokines and chemokines, including TNFα, IL-8, and GM-CSF. R406 inhibits phosphorylation of Syk substrate linker for activation of T cells in mast cells and B-cell linker protein/SLP65 in B cells. R406 binds to the ATP binding pocket of Syk and inhibits its kinase activity as an ATP-competitive inhibitor with Ki of 30 nM. R406 blocks Syk-dependent FcR-mediated activation of monocytes/macrophages and neutrophils and Bcr-mediated activation of B lymphocytes [1]. R406 significantly induces chronic lymphocytic leukemia (CLL) cell apoptosis in nurselike cells cocultures and blocks CCL3 and CCL4 secretion by CLL cells in response to B-cell antigen receptor (Bcr) triggering [2]. R406 is a potent inhibitor of platelet signaling and functions initiated by FcγRIIA cross-linking by specific antibodies or by sera from HIT patients [3].in vivo: R406 reduces cutaneous reverse passive Arthus reaction by approximately 86% at 5 mg/kg in prophylactic treated mice. R406 also shows efficacy in inhibiting paw inflammation in antibody-induced arthritis mouse models [1]. R406 does not adversely affect macrophage or neutrophil function in innate immune responses and has minimal functional immunotoxicity notwithstanding its lymphocytopenic effect [4].
Dehydroabietinol is an abietane diterpenoid. Dehydroabietinol has kinase inhibition activity for spleen tyrosine kinase (SYK) with an IC50 value of 46.4 μM. Dehydroabietinol can be used for the research of immune-mediated disease[1].
TAS05567 (TAS-5567) is a novel potent, selective, orally available Spleen tyrosine kinase (Syk) inhibitor with IC50 of 0.37 nM; shows >70% inhibition of Syk and 4 other kinases in a panel of 192 kinases, more selective and potent than R406; suppresses induction of BLNK phosphorylation by anti-IgM in Ramos cells (IC50=1.8 nM); inhibits BCR-dependent signal transduction in Ramos cells, FcγR-mediated TNF-α production in THP-1 cells, and FcεR-mediated histamine release from RBL-2H3 cells; suppresses hind-paw swelling in a dose-dependent manner, markedly reduces histopathologic scores in rheumatoid arthritis models.
Cerdulatinib (PRT062070) is a dual JAK and SYK inhibitor with IC50s of 12, 6, 8 and 32 for JAK1, 2, 3 and SYK, respectively.
PRT062607(P505-15; PRT-2607; BIIB-057) is a highly specific and potent inhibitor of Syk with IC50 of 1-2 nM; >80-fold selective for Syk than Fgr, Lyn, FAK, Pyk2 and Zap70.IC50 value: 1-2 nM [1]Target:Syk kinase inhibitorin vitro: In human whole blood, P505-15 potently inhibited B cell antigen receptor-mediated B cell signaling and activation (IC50 0.27 and 0.28 μM, respectively) and Fcε receptor 1-mediated basophil degranulation (IC50 0.15 μM) [1]. P505-15 successfully inhibited SYK-mediated B-cell receptor signaling and decreased cell viability in NHL and CLL [2]. PRT318 and P505-15 effectively antagonize CLL cell survival after BCR triggering and in nurse-like cell-co-cultures. Moreover, they inhibit BCR-dependent secretion of the chemokines CCL3 and CCL4 by CLL cells, and leukemia cell migration toward the tissue homing chemokines CXCL12, CXCL13, and beneath stromal cells. PRT318 and P505-15 furthermore inhibit Syk and extracellular signal-regulated kinase phosphorylation after BCR triggering [3].in vivo: Similar levels of ex vivo inhibition were measured after dosing in mice (Syk signaling IC50 0.32 μM). Oral administration of P505-15 produced dose-dependent anti-inflammatory activity in two rodent models of rheumatoid arthritis [1]. Oral dosing in mice prevented BCR-mediated splenomegaly and significantly inhibited NHL tumor growth in a xenograft model. In addition, combination treatment of primary CLL cells with P505-15 plus fludarabine produced synergistic enhancement of activity at nanomolar concentrations [2].
Syk Inhibitor II dihydrochloride is a potent, high selective and ATP-competitive Syk inhibitor with an IC50 of 41 nM. Syk Inhibitor II dihydrochloride inhibits 5-HT release from RBL-cells with an IC50 of 460 nM. Syk Inhibitor II dihydrochloride shows less potent against other kinases and has anti-allergic effect[1].
ER-27319 maleate is a potent, selective inhibitor of antigen or anti-IgE-mediated degranulation of rodent and human mast cells by selective inhibition of FcɛRI-mediated activation of Syk; does not inhibits the anti-CD3-induced tyrosine phosphorylation of phospholipase C-gamma1 in Jurkat T cells.
PRT062607 hydrochloride is a highly specific and potent inhibitor of purified Syk (IC50 1-2 nM).
PRT-060318 (PRT318) is a novel selective inhibitor of the tyrosine kinase Syk with an IC50 of 4 nM.
R406 is a competitive Syk inhibitor for ATP binding with a Ki of 30 nM, potently inhibits Syk kinase activity in vitro with an IC50 of 41 nM, measured at an ATP concentration corresponding to its Km value.
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[1][2][3].
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[1].
Piceatannol is a selective inhibitor of protein tyrosine kinase Syk. It could inhibit ICa,L, Ito, IKr, Ca2+ transients and Na+-Ca2+ exchange except IK1. Shows multiple biological activities such as anti-inflammatory, antiproliferative and immunomodulatory effects.In vitro: The treatment of human myeloid cells with piceatannol suppressed TNF-induced DNA binding activity of NF-κB. The effect of piceatannol was not restricted to myeloid cells, as TNF-induced NF-κB activation was also suppressed in lymphocyte and epithelial cells. Piceatannol also inhibited NF-κB activated by H2O2, PMA, LPS, okadaic acid, and ceramide. [1]
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)[1]. GSK143 dihydrochloride reduces inflammation and prevents recruitment of immune cells in the intestinal muscularis in mice[2][3].
Cerdulatinib hydrochloride (PRT062070) is a selective, oral active and reversible ATP-competitive inhibitor of dual SYK and JAK, with the 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[1][2].
SRX3207 is an orally active and first-in-class dual Syk/PI3K inhibitor. SRX3207 possesses anti-tumor activity[1].
Syk Inhibitor II is a potent, high selective and ATP-competitive Syk inhibitor with an IC50 of 41 nM. Syk Inhibitor II inhibits 5-HT release from RBL-cells with an IC50 of 460 nM. Syk Inhibitor II shows less potent against other kinases and has anti-allergic effect[1].