bFGF

451.6

DMSO : ≥ 37 mg/mL (81.93 mM)

White powder

Physiological actions of SUN11602 mimic several phenomena of the neuroprotection that is induced by bFGF. SUN11602 plays a pivotal role in allowing primary cultured neurons to survive in adverse environments of glutamate toxicity and activating intracellular key molecules that are involved in the neuroprotective mechanisms. These actions are quite similar to those of bFGF. Such neuroprotective mechanisms are specific and distinctive to SUN11602 and bFGF and differs clearly from those of the other growth factors that are investigated. But unlike bFGF, SUN11602 can either directly or indirectly trigger the phosphorylation of the cytosolic domain of the FGFR without binding to the extracellular domain of the FGFR-1. SUN11602 demonstrates no cell proliferative activity of somatic cells, unlike bFGF. SUN11602 significantly affects neuronal survival in adverse conditions through a FGFR1-mitogen-activated protein kinase/extracellular signal-regulated kinase-1/2 kinase (FGFR-1–MEK/ERK) signaling pathway.

In WT mice, SUN11602 and bFGF increase the levels of newly synthesized Calb in cerebrocortical neurons and suppress the glutamate-induced rise in intracellular Ca²⁺. This Ca²⁺-capturing ability of Calb allows the neurons to survive severe toxic conditions of glutamate. In contrast, Calb levels remain unchanged in Calb-/- mice after exposure to SUN11602 or bFGF, and due to a loss of function of the gene, these neurons are no longer resistant to toxic conditions of glutamate. Neuroprotective activities of SUN11602 and FGF-2 are due to exogenously induced hyperexpression of CalB in hippocampal neurons. The pharmacokinetic properties of SUN11602 appear to hold promise in terms of bioavailability (>65%) after oral administration in rodents (rats and mice) and dogs (beagles).

C₂₆H₃₇N₅O₂

704869-38-5