K252a and Staurosporine Microbial Alkaloid Toxins as Prototype of Neurotropic Drugs

Brain-derived neurotrophic factor and TrkB receptor in experimental autoimmune encephalomyelitis and multiple sclerosis

“…In addition, K252a induces a delayed onset and a reduction in the clinical severity of EAE [137], which suggests a possible role for this molecule in MS treatment. The effects of therapies that enhance BDNF support or inhibit the BDNF/TrkB axis in EAE are summarized in Table 6.…”

“…Effect of BDNF gene delivery into the brain through bone marrow stem cells [14] • Delayed onset of EAE • Reduction in clinical severity • Inhibition of pro-inflammatory cytokine expression (TNF-α, IFN-γ) • Enhancement of expression of anti-inflammatory cytokines (IL-4, IL-10, IL-11) • Reduction of demyelination and increased remyelination Effect of conditional BDNF gene deletion (Cre/LoxP mice) in T cell lineage in EAE [77] • Reduction in neuroinflammation • Reduction of T cell infiltration • Reduction of T cell proliferation • Reduction of in vitro cytokine production Effect of K252a treatment in EAE [137] • Delayed onset of EAE • Reduction in clinical severity BDNF: brain-derived nurotrophic factor; EAE: experimental autoimmune encephalomyelitis; TrkB: tropomyosin-related kinase receptor B. and capacity for colony formation in lung carcinoma cell lines that express BDNF and TrkB [136]. In addition, K252a induces a delayed onset and a reduction in the clinical severity of EAE [137], which suggests a possible role for this molecule in MS treatment.…”

Analysis of the histamine H2-receptor in human monocytes

“…Moreover, we incubated monocytes with HA and structurally different PKA inhibitors, i.e. Rp-cAMPS and Rp-8-Br-cAMPS [44], H89 [45] and KT5720 [46]. H89 and KT5720 reduced fMLP-induced ROS production, whereas Rp-cAMPS and Rp-8-Br-cAMPS increased ROS release (Fig.…”

TrkB antibody elicits cytotoxicity and suppresses migration/invasion of transitional cell carcinoma cells

“…Indolocarbazole alkaloid K252a was widely used as the Trk family inhibitor in neuroscience and cancer studies (22,23). However, K252a is also a potent inhibitor of protein kinases, e.g, protein kinase C (PKC) (24), and myosin light chain kinase (MLCK) (25). It also inhibits the phosphorylation of c-met protein (MET) (26).…”