a(CHEBI:"2-[[7-(3,4-dimethoxyphenyl)-5-imidazo[1,2-c]pyrimidinyl]amino]-3-pyridinecarboxamide")

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Name

2-[[7-(3,4-dimethoxyphenyl)-5-imidazo[1,2-c]pyrimidinyl]amino]-3-pyridinecarboxamide

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chebi

Namespace Version

20180906

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https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/chebi-names.belns

The Syk inhibitor BAY61-3606 was used as a positive control in the Syk activity assay, and a dose-dependent inhibition of Syk activity was observed with BAY61-3606 as expected (Fig. 5B). PubMed:25331948

We found that, like (-)-nilvadipine, Syk inhibition with the selective Syk inhibitor BAY61-3606 resulted in decreased sAPPβ secretion, BACE-1 mRNA, and BACE-1 protein expression (data not shown). PubMed:25331948

In addition, we verified that pharmacological inhibition of Syk with BAY61-3606 resulted in a blockade of NFkB activation and that genetic down-regulation of SYK using shRNA also prevented NFkB activation (data not shown) thus highlighting Syk as a key player of NFkB activation. PubMed:25331948

We found that Syk inhibition with the selective Syk inhibitor BAY61-3606 suppresses Aβ production in 7W CHO cells overexpressing APP (Fig. 6A). PubMed:25331948

We show that the selective Syk inhibitor BAY61-3606 stimulates the transport of Aβ across the BBB in vitro mimicking the biological activity of (-)-nilvadipine in this model (Fig. 7A). PubMed:25331948

We found that, like (-)-nilvadipine, Syk inhibition with the selective Syk inhibitor BAY61-3606 resulted in decreased sAPPβ secretion, BACE-1 mRNA, and BACE-1 protein expression (data not shown). PubMed:25331948

We found that, like (-)-nilvadipine, Syk inhibition with the selective Syk inhibitor BAY61-3606 resulted in decreased sAPPβ secretion, BACE-1 mRNA, and BACE-1 protein expression (data not shown). PubMed:25331948

We found that, like (-)-nilvadipine, Syk inhibition with the selective Syk inhibitor BAY61-3606 resulted in decreased sAPPβ secretion, BACE-1 mRNA, and BACE-1 protein expression (data not shown). PubMed:25331948

We observed that BAY61-3606 significantly reduces brain Aβ38, Aβ40, and Aβ42 levels in Tg PS1/ APPsw mice (Fig. 7, C and D). PubMed:25331948

We observed that BAY61-3606 significantly reduces brain Aβ38, Aβ40, and Aβ42 levels in Tg PS1/ APPsw mice (Fig. 7, C and D). PubMed:25331948

In addition, we found that BAY61-3606 stimulates the clearance of Aβ across the BBB in wild-type mice as demonstrated by increased circulating plasma levels of human Aβ42 in mice treated with the Syk inhibitor compared with vehicle-treated mice following the intracranial injection of human Aβ42 (Fig. 7B) PubMed:25331948

We observed that BAY61-3606 significantly reduces brain Aβ38, Aβ40, and Aβ42 levels in Tg PS1/ APPsw mice (Fig. 7, C and D). PubMed:25331948

We observed a reduction in Tau phosphorylation at the Tyr-18 epitope as expected (Fig. 8) in BAY61-3606-treated mice. PubMed:25331948

Interestingly, we also detected a reduction in Tau phosphorylation at PHF-1 (Ser(P)- 396/Ser(P)-404) and CP13 (Ser(P)-202) in epitopes following treatment of Tg Tau P301S mice with BAY61-3606, whereas the RZ3 (Thr(P)-231) Tau epitope was not significantly impacted (Fig. 8) suggesting that Syk inhibition may also control the activity of other downstream kinases involved in Tau hyperphosphorylation PubMed:25331948

Interestingly, we also detected a reduction in Tau phosphorylation at PHF-1 (Ser(P)- 396/Ser(P)-404) and CP13 (Ser(P)-202) in epitopes following treatment of Tg Tau P301S mice with BAY61-3606, whereas the RZ3 (Thr(P)-231) Tau epitope was not significantly impacted (Fig. 8) suggesting that Syk inhibition may also control the activity of other downstream kinases involved in Tau hyperphosphorylation PubMed:25331948

Interestingly, we also detected a reduction in Tau phosphorylation at PHF-1 (Ser(P)- 396/Ser(P)-404) and CP13 (Ser(P)-202) in epitopes following treatment of Tg Tau P301S mice with BAY61-3606, whereas the RZ3 (Thr(P)-231) Tau epitope was not significantly impacted (Fig. 8) suggesting that Syk inhibition may also control the activity of other downstream kinases involved in Tau hyperphosphorylation PubMed:25331948

Interestingly, we also detected a reduction in Tau phosphorylation at PHF-1 (Ser(P)- 396/Ser(P)-404) and CP13 (Ser(P)-202) in epitopes following treatment of Tg Tau P301S mice with BAY61-3606, whereas the RZ3 (Thr(P)-231) Tau epitope was not significantly impacted (Fig. 8) suggesting that Syk inhibition may also control the activity of other downstream kinases involved in Tau hyperphosphorylation PubMed:25331948

We observed that pharmacological inhibition of Syk with BAY61-3606 stimulates Ser-9 phosphorylation of GSK3β in SH-SY5Y cells (Fig. 9,Aand B) suggesting that blocking Syk activity results in GSK3β inhibition. PubMed:25331948

We found that KT5270 effectively suppressed GSK3β phosphorylation at Ser-9 induced by BAY61-3606 (Fig. 10B) suggesting that this event is mediated by an activation of PKA. PubMed:25331948

We further confirmed that possibility by showing that Tau phosphorylation at the typical GSK3β sites (PHF-1 and CP13) is reduced following treatment of SH-SY5Y cells with BAY61-3606, whereas Tau phosphorylation at the RZ3 site was not significantly impacted in SH-SY5Y cells (Fig. 9C). PubMed:25331948

We further confirmed that possibility by showing that Tau phosphorylation at the typical GSK3β sites (PHF-1 and CP13) is reduced following treatment of SH-SY5Y cells with BAY61-3606, whereas Tau phosphorylation at the RZ3 site was not significantly impacted in SH-SY5Y cells (Fig. 9C). PubMed:25331948

We further confirmed that possibility by showing that Tau phosphorylation at the typical GSK3β sites (PHF-1 and CP13) is reduced following treatment of SH-SY5Y cells with BAY61-3606, whereas Tau phosphorylation at the RZ3 site was not significantly impacted in SH-SY5Y cells (Fig. 9C). PubMed:25331948

We further confirmed that possibility by showing that Tau phosphorylation at the typical GSK3β sites (PHF-1 and CP13) is reduced following treatment of SH-SY5Y cells with BAY61-3606, whereas Tau phosphorylation at the RZ3 site was not significantly impacted in SH-SY5Y cells (Fig. 9C). PubMed:25331948

We found that treatment of SH-SY5Y cells with BAY61-3606 inhibits AKT phosphorylation (Fig. 9, A and B), which is consistent with previous studies (59) investigating the impact of Syk inhibition on AKT activation. PubMed:25331948

We found that Syk inhibition with BAY61-3606 induced CREB phosphorylation, although that event is inhibited in the presence of a selective PKA inhibitor (Fig. 10, A and B) further showing that Syk inhibition results in PKA activation. PubMed:25331948