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Chemical Structure| 219766-25-3 Chemical Structure| 219766-25-3

Structure of ANA-12
CAS No.: 219766-25-3

Chemical Structure| 219766-25-3

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ANA-12 is a selective TrkB receptor antagonist with an IC50 value of 45 nM for TrkB. ANA-12 exhibits neuroprotective and antidepressant effects and can be used in research on neurodegenerative diseases and mood disorders.

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Product Citations

Product Citations

Zhang, Aomei ; Yang, Jingwen ; Wang, Meng ; Li, Yujia ; Hu, Tao ; Xie, Jialin , et al.

Abstract: N4-acetylation of Cytidine (ac4C), catalyzed by its only known enzyme N-acetyltransferase 10 (NAT10), facilitates cellular mRNA translation and stability, but its function in brain disorders especially epilepsy is poorly understood. By using pentylenetetrazole (PTZ) induced mouse model of epilepsy, we first displayed spatiotemporally expression of ac4C and NAT10 in the mouse brain. To corroborate the alteration of ac4C and NAT10 in epilepsy, we used acute PTZ, chronic PTZ and intrahippocampal kainic acid (IHKA) mouse model. We then utilized a combination of viral tool and pharmacological approaches to implicate NAT10 mediated ac4C modification in seizure behaviors. We found that the expression of ac4C was increased in epileptic brain tissues in mouse models of epilepsy, which might be due to the up-regulated NAT10. Block of NAT10 led to both reduced brain ac4C level and resistance to PTZ or KA-induced seizure behavior, while hippocampal over-expression of NAT10 causes exacerbated seizure behavior. In support of such a role, our data demonstrated that the loss or gains of ac4C modification could normalize or exacerbate neuronal over-activation in epileptic brain tissues, respectively. Mechanically, we observed that block the NAT10 or over-expression NAT10 lead to reduced or enhanced BDNF, respectively. While the BDNF pathway inhibitor rescued the hippocampal NAT10 over-expression induced aggravated seizure behavior in the chronic PTZ treated mice. Therefore, our work provides the first demonstration of the ac4C levels in an epilepsy mice model, targeted to prevent ac4C by NAT10 inhibition seems to be effective in preventing and treating epilepsy.

Keywords: ac4C ; NAT10 ; Seizure ; Hippocampus ; IEGs

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Product Details of ANA-12

CAS No. :219766-25-3
Formula : C22H21N3O3S
M.W : 407.49
SMILES Code : O=C(C1=CC2=CC=CC=C2S1)NC3=CC=CC=C3C(NC4C(NCCCC4)=O)=O
MDL No. :MFCD00117444
InChI Key :TUSCYCAIGRVBMD-UHFFFAOYSA-N
Pubchem ID :2799722

Safety of ANA-12

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Related Pathways of ANA-12

RTK

Isoform Comparison

Biological Activity

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Rats cocaine self-administration model Intraperitoneal injection 0.5 mg/kg 4 hours prior to each of 10 daily sessions ANA-12 administration reversed the diminished self-administration of cocaine in ♂CocSired rats. PMC3531046
Mice intracerebral hemorrhage (ICH) Intraperitoneal injection 0.5 mg/kg/day daily for 7 days, starting 1 day before ICH to investigate the effects of ANA-12 on WIM after ICH and TrkB activity after ICH. PMC8383380
Sprague-Dawley rats Cyclophosphamide-induced cystitis model Intraperitoneal injection 0.5 mg/kg Every other day for 3 days ANA-12 could attenuate mechanical allodynia, restrain activation of astrocytes and microglia and alleviate neuroinflammation. PMC6958761
Mice Early-life stress model Intraperitoneal injection 0.5 mg/kg Single dose To examine the effects of TrkB receptor inhibition on spatial memory, results showed that ANA-12 significantly decreased preference index, mimicking the cognition-impairing effects of ELS. PMC10209152

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.45mL

0.49mL

0.25mL

12.27mL

2.45mL

1.23mL

24.54mL

4.91mL

2.45mL

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