Autophagy activator-2
Autophagy activator-2 is a potent autophagy activator with EC50 values of 14.33 μM. Autophagy activator-2 acts as a proteostasis modulator and small-molecule chaperone that upregulates I1061T mutant NPC1 expression and facilitates cholesterol efflux. Autophagy activator-2 reduces lysosomal hydrolase levels. Autophagy activator-2 can be used for the study of Niemann-Pick Type C disease.
For research use only. We do not sell to patients.
- CAS No.: 1111050-17-9
- Formula: C22H36N6OS
- Molecular Weight:432.63
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Autophagy activator-2 (compound 2) induces autophagosome formation in eGFP-LC3 HeLa cells with an EC50 of 14.33 μM, acting as an autophagy activator near its EC50 and a late-stage inhibitor at higher concentrations[1].
Autophagy activator-2 (20, 40 μM; 6 h in HeLa cells; 20 μM; 24 h in fibroblasts) slightly reduces lysosomal proteolytic activity in wild-type HeLa cells at 20 and 40 μM but significantly enhances proteolytic activity in NPC1I1061T fibroblasts at 20 μM[1].
Autophagy activator-2 (10-80 μM; 24 h) is noncytotoxic to NPC1 fibroblasts[1].
Autophagy activator-2 (80 μM; 24 h) does not inhibit mTOR kinase activity in NPC1I1061T fibroblast[1].
Autophagy activator-2 (80 μM; 24 h) reduces expression of multiple lysosomal hydrolases and increases glycosylated LAMP1 levels in NPC1I1061T fibroblasts[1].
Autophagy activator-2 (80 μM; 24 h) does not reduce unesterified cholesterol accumulation in NPC1 null HeLa cells, demonstrating its activity is dependent on NPC1 expression[1].
Autophagy activator-2 (10, 20 μM; 24 h) increases Endo H-sensitive NPC1 protein levels in fibroblasts, without affecting wild-type NPC1 expression[1].
Autophagy activator-2 (40, 80 μM; 24 h) does not broadly suppress proteasomal or autophagic degradation or alter ATF4 expression in I1061T NPC1 mutant fibroblasts, while elevating the LC3-II/LC3-I ratio and showing no enhanced ER stress[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:I1061T NPC1 patient-derived fibroblasts
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Concentration:10, 20, 40, 80 μM
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Incubation Time:24 h
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Result:Maintained ≥ 80% cell viability at all tested concentrations, showing no cytotoxicity at doses that produce beneficial phenotypic effects.
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Cell Line:I1061T NPC1 patient-derived fibroblasts
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Concentration:80 μM
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Incubation Time:24 h
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Result:Did not significantly decrease the formation of phosphorylated p70S6K, indicating no significant inhibition of mTOR kinase activity.\n
Significantly reduced protein expression levels of lysosomal hydrolases including legumain (LGMN), cathepsin Z (CTSZ), cathepsin B (CTSB), and cathepsin D (CTSD).
Increased levels of glycosylated lysosomal-associated membrane protein 1 (LAMP1).
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Cell Line:I1061T NPC1 patient-derived fibroblasts
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Concentration:10, 20 μM
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Incubation Time:24 h
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Result:Increased NPC1 protein intensity to ~1.7-fold at 10 μM and ~1.4-fold at 20 μM compared to DMSO treatment.
Increased Endo H-sensitive (ER-retained) I1061T NPC1, with no effect on wild-type NPC1 expression.
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Cell Line:I1061T NPC1 patient-derived fibroblasts
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Concentration:40, 80 μM
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Incubation Time:24 h
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Result:Did not cause accumulation of p21, p27, or p62, indicating no broad inhibition of proteasomal or autophagic degradation.
Increased the LC3-II/LC3-I ratio at both 40 and 80 μM, consistent with autophagy modulation.\n
Did not significantly alter ATF4 expression levels compared to DMSO treatment, indicating no exacerbation of ER stress.
Chemical Information
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CAS No. 1111050-17-9
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Molecular Weight 432.63
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Formula C22H36N6OS
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SMILES
CCCCN(CC)CCCNC(C1=C(C)C2=C(N3CCN(C)CC3)N=CN=C2S1)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)