ATI-1
ATI-1 is an autophagy initiation inhibitor. ATI-1 targets valosin-containing protein (VCP/p97, disrupts its interaction with UFL1, impairs UFMylation homeostasis associated with VCP, promotes polyubiquitination and degradation of Beclin1, and blocks the formation of early autophagosomes. ATI-1 induces synergistic death of autophagy-dependent malignant tumor cells under nutrient deprivation conditions, accompanied by decreased mitochondrial membrane potential, reduced ROS levels and lysosomal stress. ATI-1 exhibits anti-tumor efficacy in a pancreatic adenocarcinoma xenograft mouse model. ATI-1 can be used for the research of pancreatic adenocarcinoma and lung cancer.
For research use only. We do not sell to patients.
- CAS No.: 1242983-93-2
- Formula: C16H14F2N2O2S3
- Molecular Weight:400.49
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
ATI-1 (10 μM; 20 h, plus 20 μM CQ final 4 h) potently inhibits autophagosome formation in HeLa cells[1].
ATI-1 (5-20 μM; 24 h, plus 10 μM for 2 h under EBSS starvation) inhibits autophagy initiation in HeLa cells by reducing Beclin1 protein levels and suppressing autophagosome formation, with dose-dependent reductions in LC3II levels at 5, 10, 20 μM over 24 h, and paradoxical LC3II accumulation under starvation that does not reflect functional autophagosome formation[1].
ATI-1 (5-20 μM; 48 h, plus CQ co-treatment) robustly inhibits autophagy initiation in autophagy-addicted NCI-H1299 and MIA PaCa-2 cells by reducing Beclin1 protein levels, with dose-dependent reductions in LC3II levels at 5, 10, 20 μM over 48 h, and suppressed autophagosome formation in MIA PaCa-2 cells when combined with CQ[1].
ATI-1 (20 μM; 48-72 h) selectively inhibits proliferation, clonogenic capacity, migration, and invasion of autophagy-addicted NCI-H1299 and MIA PaCa-2 cells, with greater potency than in less autophagy-dependent HeLa cells[1].
ATI-1 (30 μM; 24 h) disrupts the VCP-UFL1 interaction, reduces VCP UFMylation, weakens the VCP-Beclin1 interaction, and selectively impairs specific VCP cofactor interactions (VCP-ATXN3, VCP-NPLOC4) in HeLa cells[1].
ATI-1 (3.13-50 μM) directly binds to purified full-length VCP (Kd = 25.1 μM) and purified VCP N-terminal domain (Kd = 32.5 μM) with measurable affinity[1].
ATI-1 (20 μM; 48 h) induces G1-phase arrest but does not trigger significant apoptosis in autophagy-addicted NCI-H1299 and MIA PaCa-2 cells[1].
ATI-1 (5-10 μM; 2-24 h) exacerbates metabolic vulnerability of autophagy-addicted NCI-H1299 and MIA PaCa-2 cells under EBSS-induced nutrient deprivation, leading to non-apoptotic cell death, reduced mitochondrial membrane potential, lower ROS levels, and lysosomal stress, with 5 μM ATI-1 reducing cell viability by ~50-70% over 24 h when combined with starvation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HeLa cells
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Concentration:10 μM; 20 μM CQ (final 4 h)
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Incubation Time:20 h; 4 h (CQ)
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Result:Markedly reduced the number of autophagosomes per cell.
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Cell Line:HeLa cells
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Concentration:10 μM (with 10 μM CQ final 2 h); 5, 10, 20 μM; 20 μM; 10 μM (EBSS starvation)
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Incubation Time:24 h; 24 h; 24 h; 2 h (EBSS starvation)
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Result:Prevented LC3II accumulation seen in the CQ-only group at 10 μM for 24 h with 10 μM CQ for the final 2 h.
Induced a dose-dependent reduction in LC3II levels at 5, 10, 20 μM for 24 h.
Reduced Beclin1 protein levels at 20 μM for 24 h.
Caused a paradoxical accumulation of LC3II under EBSS starvation at 10 μM for 2 h, but autophagic flux analysis confirmed reduced LC3 puncta.
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Cell Line:NCI-H1299 cells, MIA PaCa-2 cells
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Concentration:5, 10, 20 μM (NCI-H1299); 10 μM (NCI-H1299, with 10 μM CQ final 2 h); 5, 10, 20 μM (MIA PaCa-2); 10 μM (MIA PaCa-2, with 10 μM CQ final 2 h); 10 μM (MIA PaCa-2, with 20 μM CQ final 6 h); 20 μM (NCI-H1299, MIA PaCa-2)
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Incubation Time:48 h (NCI-H1299); 48 h (NCI-H1299, plus 2 h CQ); 48 h (MIA PaCa-2); 48 h (MIA PaCa-2, plus 2 h CQ); 48 h (MIA PaCa-2, plus 6 h CQ); 48 h (NCI-H1299, MIA PaCa-2)
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Result:Induced a dose-dependent reduction in LC3II levels in both NCI-H1299 and MIA PaCa-2 cells over 48 h.
Significantly reduced LC3II levels in MIA PaCa-2 cells at 10 μM for 48 h with 10 μM CQ for the final 2 h, with less pronounced effect in NCI-H1299 cells.
Reduced yellow autophagosome/autolysosome puncta in MIA PaCa-2 cells at 10 μM for 48 h with 20 μM CQ for the final 6 h compared to CQ alone.
Markedly decreased Beclin1 protein levels in both cell lines at 20 μM for 48 h.
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Cell Line:NCI-H1299 cells, MIA PaCa-2 cells, HeLa cells
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Concentration:20 μM
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Incubation Time:72 h (CCK-8); 48 h (colony formation, wound healing, Transwell assays)
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Result:Showed more pronounced growth-inhibitory effects in NCI-H1299 and MIA PaCa-2 cells than in HeLa cells, with lower IC50 values across time points.
Significantly inhibited proliferation of NCI-H1299 and MIA PaCa-2 cells at 20 μM for 48 h, while HeLa cells remained relatively resistant.
Markedly abrogated long-term clonogenic capacity and significantly impaired migratory and invasive potential of NCI-H1299 and MIA PaCa-2 cells.
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Cell Line:NCI-H1299 cells, MIA PaCa-2 cells
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Concentration:20 μM
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Incubation Time:48 h
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Result:Led to G1-phase arrest in both cell lines.
Did not induce obvious apoptosis, with no significant increase in apoptotic populations compared to controls.
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Cell Line:NCI-H1299 cells, MIA PaCa-2 cells
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Concentration:20 μM
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Incubation Time:12 h, 24 h, 48 h
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Result:Did not increase γH2AX levels at any time point.
Had little effect on ATXN3 abundance, unlike the canonical VCP inhibitor NMS-873 which induced robust γH2AX and reduced ATXN3 levels.
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Cell Line:NCI-H1299 cells, MIA PaCa-2 cells
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Concentration:10 μM (LC3, ROS, lysosomal, mitochondrial assays); 5 μM (cell viability, apoptosis assays)
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Incubation Time:2 h (LC3, ROS, lysosomal, mitochondrial assays); 24 h (cell viability, apoptosis assays)
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Result:Enhanced LC3II accumulation compared to EBSS alone when co-treated with ATI-1 and EBSS.
Reduced cell viability by ~50% within 24 h at 5 μM, and up to ~70% in MIA PaCa-2 cells.
No significant increase in apoptotic populations was observed.
Decreased mitochondrial membrane potential, reduced ROS levels, and caused lysosomal stress with impaired membrane integrity and reduced acidic staining when combined with EBSS.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Nude mice[1]
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Dosage:50 mg/kg
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Administration:i.p.; daily; 14 days
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Result:Significantly suppressed tumor growth, resulting in reduced final tumor weights and volumes compared to controls.
Markedly reduced intratumoral LC3 and Ki-67 expression.
Caused no significant body weight loss or pathological abnormalities in major organs (heart, liver, spleen, lungs, kidneys).
Chemical Information
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CAS No. 1242983-93-2
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Molecular Weight 400.49
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Formula C16H14F2N2O2S3
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SMILES
FC1=CC(F)=CC(NS(=O)(C2=CC=C(C3=NC(C(C)C)=CS3)S2)=O)=C1
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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)
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