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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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Liu, Shen ; Huang, Tingmo ; Wan, Liyang ; Xiong, Yinghong ; Zeng, Liyue ; Du, Ruixue , et al.

Abstract: Background: Rotator cuff injury (RCI) often leads to chronic pain and anxiety, yet the underlying neural mechanisms remain unclear. This study explored central mechanisms linking RCI to these symptoms and assessed treadmill exercise (TE) as a therapeutic intervention in mice. Methods: Male C57BL/6 mice underwent RCI surgery and were randomized into Sham, RCI, or TE groups (TE initiated on postoperative day 7). Mechanical hypersensitivity and anxiety-like behaviors were evaluated via von Frey, elevated plus maze, and open field tests. Synaptic plasticity proteins and structures in the paraventricular nucleus (PVN) were analyzed using immunofluorescence, Western blotting, electron microscopy, and Golgi staining. The brain-derived neurotrophic factor-tropomyosin receptor kinase B (BDNF-TrkB) pathway’s role was tested using the TrkB inhibitor ANA-12. Results: RCI elicited notable alterations in synaptic structure within the PVN, characterized by decreased synaptophysin expression, increased growth-associated protein 43 expression, and synaptic microstructural abnormalities. These synaptic modifications were correlated with the manifestation of hyperalgesia and anxiety-like behaviors in murine models. TE reversed these synaptic changes and improved pain and anxiety symptoms. Mechanistically, TE activated the BDNF-TrkB signaling pathway in the PVN, which was essential for its therapeutic effects. Pharmacological blockade of the TrkB receptor using ANA-12 attenuated the therapeutic benefits of TE, confirming the critical role of BDNF-TrkB signaling pathway. Conclusion: TE mitigates RCI-related pain and anxiety by restoring PVN synaptic plasticity via BDNF-TrkB signaling, underscoring exercise’s therapeutic potential. The translational potential of this article: The study reveals new insights into the central neural mechanisms of pain and anxiety after RCI, highlighting synaptic plasticity changes in the PVN. It clarifies the link between peripheral injury and central nervous system alterations, guiding clinicians toward more targeted and effective treatments.

Keywords: Rotator cuff injury ; Pain ; Anxiety ; Structural plasticity ; Treadmill exercise

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

Abstract: N4-acetylation of (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. Nat Neurosci. 2013 Jan;16(1):42-7
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. J Neuroinflammation. 2020 Jan 13;17(1):19
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. Transl Psychiatry. 2023 May 24;13(1):173
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. J Neuroinflammation. 2021 Aug 23;18(1):184

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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