1. NF-κB Neuronal Signaling
  2. NF-κB Beta-secretase
  3. (S)-(-)-Anatabine

(S)-(-)-Anatabine is an NFκB/BACE-1 inhibitor with blood-brain barrier penetration. (S)-(-)-Anatabine inhibits NFκB activation via phosphorylation of its p65 subunit. (S)-(-)-Anatabine inhibits BACE-1 transcription and reduces BACE-1 protein levels. (S)-(-)-Anatabine lowers production of 1-40 and 1-42 by reducing β-cleavage of amyloid precursor protein without affecting α-cleavage. (S)-(-)-Anatabine can be used for the research of Alzheimer's disease.

For research use only. We do not sell to patients.

(S)-(-)-Anatabine

(S)-(-)-Anatabine Chemical Structure

CAS No. : 581-49-7

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Description

(S)-(-)-Anatabine is an NFκB/BACE-1 inhibitor with blood-brain barrier penetration. (S)-(-)-Anatabine inhibits NFκB activation via phosphorylation of its p65 subunit. (S)-(-)-Anatabine inhibits BACE-1 transcription and reduces BACE-1 protein levels. (S)-(-)-Anatabine lowers production of 1-40 and 1-42 by reducing β-cleavage of amyloid precursor protein without affecting α-cleavage. (S)-(-)-Anatabine can be used for the research of Alzheimer's disease[1].

IC50 & Target[1]

NF-κB

 

BACE1

 

In Vitro

(S)-(-)-Anatabine (24 h) dose-dependently reduces Aβ1-40 and Aβ1-42 production with an IC50 of 640 μg/mL[1].
(S)-(-)-Anatabine (200-800 μg/mL; 3 h) dose-dependently inhibits TNFα-induced NFκB activation in HEK293 NFκB luciferase reporter cells[1].
(S)-(-)-Anatabine (600 μg/mL; 24 h) inhibits basal p65 NFκB phosphorylation in 7W CHO cells overexpressing human APP, and inhibits TNFα-induced p65 NFκB phosphorylation in HEK293 and SHSY-5Y cells[1].
(S)-(-)-Anatabine (500-1000 μg/mL; 30 min) fully inhibits TNFα-induced BACE-1 transcription in human neuronal-like SHSY-5Y cells[1].
(S)-(-)-Anatabine (5-1000 μg/mL; 24 h) dose-dependently reduces BACE-1 protein levels in human neuronal-like SHSY-5Y cells[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis[1]

Cell Line: 7W CHO cells overexpressing human APP, HEK293 cells, human neuronal-like SHSY-5Y cells
Concentration: 600 μg/mL
Incubation Time: 24 h
Result: Significantly reduced basal p65 NFκB phosphorylation relative to controls in 7W CHO cells.
Significantly reduced TNFα-induced p65 NFκB phosphorylation relative to TNFα-only treatment in HEK293 and SHSY-5Y cells.

Real Time qPCR[1]

Cell Line: human neuronal-like SHSY-5Y cells
Concentration: 500 μg/mL; 1000 μg/mL
Incubation Time: 30 min
Result: Fully prevented the TNFα-induced increase in BACE-1 mRNA levels at both 500 μg/mL and 1000 μg/mL.
Showed no significant difference in BACE-1 mRNA levels between control cells and cells treated with TNFα + anatabine.

Western Blot Analysis[1]

Cell Line: human neuronal-like SHSY-5Y cells
Concentration: 5 μg/mL; 20 μg/mL; 50 μg/mL; 100 μg/mL; 200 μg/mL; 800 μg/mL; 1000 μg/mL
Incubation Time: 24 h
Result: Reduced BACE-1 protein levels dose-dependently.
Caused statistically significant reductions in BACE-1 protein levels relative to controls at all doses higher than 50 μg/mL.
Parmacokinetics
Species Dose Route AUC0-∞ (Brain) Cmax (Brain) AUC0-∞ (Plasma) Cmax
Mice[1] 2 mg/kg i.v. 172384 min·ng/mL 5194.4 ng/mL 49968 min·ng/mL 1501.7 ng/mL
In Vivo

(S)-(-)-Anatabine (2 mg/kg; i.p.; single dose) can cross the blood–brain barrier, with the area under the curve (AUC)
and the maximal concentration (Cmax) achieving approximately 3.5 times greater in the brain of B6/SJL F1 mice than in the plasma[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: B6/SJL F1 mice (43 week-old)[1]
Dosage: 2 mg/kg
Administration: i.p.; single dose
Result: Exhibited AUC of 172384.9 ng·min/mL and 49968 ng·min/mL in the brain and plasma, respectively.
Exhibited Cmax of 5194.4 ng/mL and 1501.7 ng/mL in the brain and plasma, respectively.
Molecular Weight

160.22

Formula

C10H12N2

CAS No.
SMILES

[C@@H]1(C2=CC=CN=C2)CC=CCN1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation
References
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    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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(S)-(-)-Anatabine
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HY-126047
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