SUN11602

SKU: orb1303858

Description

SUN11602 is a neuroprotective small molecule that mimics bFGF by activating the FGFR-ERK1/2 pathway and upregulating CALB1. It protects cerebrocortical neurons from glutamate-induced excitotoxicity, making it a useful research tool for studying neuroprotection in models of neurological disorders.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 704869-38-5
• MW: 451.6
• Purity: 99.36% (May vary between batches)
• Formula: C₂₆H₃₇N₅O₂
• SMILES: CN(C1CCN(Cc2ccc(cc2)C(N)=O)CC1)C(=O)CNc1c(C)c(C)c(N)c(C)c1C
• Target: FGFR,ERK
• Solubility: DMSO:40 mg/mL (88.57 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.43 mM);Ethanol:9 mg/mL (19.93 mM)

Bioactivity

• In Vivo:
  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).
• In Vitro:
  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.
• Cell Research:
  Actinomycin D or cycloheximide is first added to the cultures, and, 2 h later, SUN11602 or bFGF is added. After a 24 h incubation, neurons in the cultures are exposed to 150 μM glutamate for another 24 h, and cell viability is determined by a (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay.(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

SUN 11602, SUN11602, SUN-11602, inhibit, Inhibitor, FGFR, Fibroblast growth factor receptor, ERK1, ERK2

Compound Identifiers

PubChem CID

22245705