product name ANA-12
Description: ANA-12 is a potent and selective TrkB antagonist with Kd of 10 nM and 12 μM for the high and low affinity sites, respectively. Mice administered ANA-12 demonstrated reduced anxiety- and depression-related behaviors on a variety of tests predictive of anxiolytic and antidepressant properties in humans. ANA-12 may be a valuable tool for studying BDNF/TrkB signaling and may constitute a lead compound for developing the next generation of therapeutic agents for the treatment of mood disorders.
References: J Clin Invest. 2011 May 2; 121(5): 1846–1857; Eur J Neurosci. 2014 May;39(9):1439-54.
407.49
Formula
C22H21N3O3S
CAS No.
219766-25-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 37 mg/mL (90.79 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: ANA-12 binds directly and selectively to TrkB and inhibits processes downstream of TrkB without altering TrkA and TrkC functions. In nnr5 PC12-TrkB cells, ANA-12 prevents brain-derived neurotrophic factor (BDNF)-induced neurite outgrowth at concentrations as low as 10 nM. In DRG neurons, ANA-12 eliminates the effect of BDNF on increasing inward current. Kinase Assay: Maxisorp ELISA 96-well plates are coated with various concentrations of Trk BECD -Fc, 20 mg/ml BSA, or 1 mg/mL IgG-Fc (polyclonal anti-TrkB) in a carbonate buffer (pH 9.6) overnight at 4°C. Plates are saturated with 0.5% BSA in PBS for 2 hours at room temperature and extensively washed in PBS-Tween 0.05%. Bodipy–ANA-12 is then incubated in 0.5% PBS-BSA for 1 hour at room temperature before the addition of BDNF in 0.5% PBS-BSA for another hour. After extensive washes in PBS-Tween 0.05%, the amount of bodipy–ANA-12 bound is quantified by fluorescence at 520 ± 10 nm. Detectability range for extrapolation analysis is assessed by coating ELISA plates with bodipy–ANA-12 and reading fluorescence at 520 ± 10 nm. Cell Assay: Modulation of neurite outgrowth by molecules is assessed in nnr5 PC12–TrkB, –TrkA, and –TrkC cells after addition of BDNF (1 nM), NGF (2 nM), and NT-3 (10 nM), respectively. The number of cells bearing neurites longer than 2 cells in diameter in each counting field is microscopically determined (2 fields per well, 3 wells per condition). Counting is performed blind each 24 hours for 3 days. |
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| In Vivo | In adult C57BL6/129SveV F1s mice, ANA-12 (0.5 mg/kg, i.p.) decreases TrKB activity in the brain and reduces the anxiety- and depression-related behaviors without affecting the neuron survival. In male C57BL/6 mice, ANA-12 (0.5 mg/kg, i.p.) shows antidepressant-like effects on lipopolysaccharide-induced depression-like behavior. In male Sprague-Dawley rats, ANA-12 (3 μg/dose) blocks the effect of medial nucleus tractus solitarius (mNTS) BDNF on reducing food intake. In male wild-type mice, ANA-12 reverses ethanol intake and induces D3 receptor downregulation, but is ineffective in D3R-/- mice. In male CocSired rats, ANA-12 (0.5 mg/kg, i.p.) reverses the diminished self-administration of cocaine. |
| Animal model | Adult C57BL6/129SveV F1s mice |
| Formulation & Dosage | Dissolved in 1% DMSO dissolved in 0.9% NaCl solution; 0.5 mg/kg; i.p. |
| References | J Clin Invest. 2011 May 2; 121(5): 1846–1857; Eur J Neurosci. 2014 May;39(9):1439-54; Int J Neuropsychopharmacol. 2014 Oct 31;18(4). pii: pyu077. |
