UE01
UE01 is an orally active, selective small-molecule modulator targeting both ULK1/ERK1/2. UE01 activates hULK1 with an EC50 of 695.30 nM and a KD of 114.3 nM for ULK1; it inhibits hERK1 with an IC50 of 179.90 nM and a KD of 114 nM for ERK1; it shows weak binding to ERK2 with a KD of 2.8 mM. UE01 induces the conformational transition of ULK1 from an inactive to an active state, enhances the phosphorylation of ULK1 Ser317 and mAtg13 Ser355, and reduces the phosphorylation of ULK1 Ser757. UE01 competitively occupies the ATP-binding pocket of ERK1, inhibits ERK1 kinase activity, and reduces the activity of the ERK1/2 signaling pathway. UE01 induces complete autophagy flux and apoptosis, upregulates Atg5, Atg7, LC3-II/LC3-I, Bax, cytochrome C (Cyt c), Cleaved-Caspase 3, Cleaved-PARP1 and E-cadherin, downregulates p62, Bcl-2, MMP-2 and MMP-9, reduces the phosphorylation of Exo70 Ser250, and promotes the proteasome-dependent degradation of Cav-1, thereby inhibiting EMT-related phenotypes and extracellular matrix degradation. UE01 can be used in studies related to triple-negative breast cancer.
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- CAS 番号: 486440-74-8
- 分子式: C18H13BrCl2N2O2
- 分子量:440.12
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
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hULK1 695.3 nM (EC50) |
ULK1 114.3 nM (Kd, SPR) |
hERK1 179.9 nM (IC50) |
erk1 114 nM (Kd, SPR) |
ERK2 2.8 mM (Kd, SPR) |
UE01 activates human ULK1 with an EC50 of 695.30 nM, and inhibits ERK1 with an IC50 of 179.90 nM; the Kd values of UE01 for ULK1, ERK1 and ERK2 are 114.3 nM, 114 nM and 2.8 mM, respectively[1].
UE01 (20 μM; 6 h) increases the thermal stability and protease degradation resistance of ULK1, ERK1 and ERK2 in MDA-MB-231 cells, induces activation-associated conformational changes in ULK1, and competitively occupies the ATP-binding pocket of ERK1[1].
UE01 inhibits the proliferation of triple-negative breast cancer cells MDA-MB-231 and BT-549, with IC50 values of 21.86 μM and 24.24 μM, respectively[1].
UE01 (10-40 μM; 24 h) upregulates E-cadherin, downregulates MMP-2, MMP-9 and Cav-1, and reduces the phosphorylation level of Exo70 Ser250, thereby inhibiting EMT-related phenotypes and extracellular matrix degradation[1].
UE01 (20 μM; 48 h) significantly inhibits the migration of MDA-MB-231 and BT-549 cells in scratch wound healing assays, with stronger efficacy than single-target controls, and this effect is mediated by activating ULK1 and inhibiting ERK1/2/Exo70[1].
UE01 (20 μM; 48 h) significantly inhibits the migration of MDA-MB-231 cells in Transwell assays, with stronger efficacy than single-target controls, and this effect depends on the expression of ULK1 and ERK1[1].
UE01 (10-40 μM; 24 h) activates the ULK1 signaling pathway and inhibits the ERK1/2 signaling pathway in a concentration-dependent manner, and regulates metastasis-related proteins (upregulates E-cadherin, downregulates Cav-1, MMP-2, MMP-9) in MDA-MB-231 and BT-549 cells. These effects are mediated by the ULK1 and Cav-1/Exo70 pathways[1].
UE01 (20 μM; 24 h) upregulates the expression of E-cadherin and downregulates the expression of MMP-2 in MDA-MB-231 cells, and its downregulatory effect on MMP-2 is stronger than that of the single-target control[1].
UE01 (10-40 μM; 24 h) increases autophagy levels in MDA-MB-231 and BT-549 cells in a concentration-dependent manner, as determined by LC3B fluorescence assay[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDA-MB-231, BT-549 triple-negative breast cancer cells
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Concentration:10, 20, 40 μM
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Incubation Time:24 h
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Result:Concentration-dependently increased ULK1 protein abundance, phosphorylation of ULK1 (Ser317) and mAtg13 (Ser355), and E-cadherin expression in MDA-MB-231 cells.
Concentration-dependently decreased phosphorylation of ULK1 (Ser757), p-MAPK1/3 (Thr202/Tyr204), Cav-1, MMP-2, and MMP-9 expression in MDA-MB-231 cells, with no change in upstream MAPK components (Ras, c-Raf, p-c-Raf, MEK1/2, p-MEK1/2).
Concentration-dependently increased E-cadherin expression and decreased MMP-2 expression in BT-549 cells.
Had its effects on Exo70, MMP-2, and E-cadherin expression attenuated by ULK1 knockdown.
Had its inhibitory effects on MMP-2 and p-Exo70 (Ser250), and stimulatory effect on E-cadherin reversed by overexpression of Cav-1.
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Cell Line:MDA-MB-231 triple-negative breast cancer cells
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Concentration:10, 20, 40 μM
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Incubation Time:24 h
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Result:Concentration-dependently increased Atg5, Atg7, and LC3-II/LC3-I ratio.
Concentration-dependently decreased p62 expression.
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Cell Line:MDA-MB-231, BT-549 triple-negative breast cancer cells
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Concentration:10, 20, 40 μM
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Incubation Time:24 h
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Result:Concentration-dependently increased LC3B fluorescence intensity in both cell lines.
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Cell Line:MDA-MB-231 triple-negative breast cancer cells
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Concentration:10, 20, 40 μM
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Incubation Time:24 h
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Result:Concentration-dependently increased MDC fluorescence intensity, indicating enhanced autophagic activity.
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Cell Line:MDA-MB-231,
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Concentration:20 μM
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Incubation Time:24 h
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Result:Increased the proportions of early and late apoptotic cells and produced a greater total apoptosis rate than the control and LYN-1604 groups.
UE01 (25-100 mg/kg; p.o.; once daily; for 13 consecutive days) dose-dependently reduces pulmonary bioluminescent signals and the number of lung metastatic nodules, upregulates E-cadherin, downregulates MMP-2, and improves collagen fiber structure in the MDA-MB-231-Luc tail vein lung metastasis model[1].
UE01 (25-100 mg/kg; p.o.; once daily; for 13 consecutive days) does not significantly alter body weight or serum indicators of liver and kidney function in mice, but histopathological lesions are observable in liver tissues of the high-dose group[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (male, 20-22 g, subcutaneous xenograft model)[1]
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Dosage:25 mg/kg; 50 mg/kg; 100 mg/kg
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Administration:p.o.; daily; 13 days
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Result:Dose-dependently reduced tumor volume, tumor weight and tumor bioluminescence.
Reduced Ki-67, p-ERK1/2 and MMP-2 staining, increased p-ULK1 and E-cadherin staining, and increased collagen volume fraction in tumor tissues.
Did not significantly alter body weight or serum liver and renal function biomarkers, although liver histopathological lesions were observed in the 100 mg/kg group.
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Animal Model:BALB/c nude (male, 20-22 g, lung metastasis model)[1]
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Dosage:25 mg/kg; 50 mg/kg; 100 mg/kg
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Administration:p.o.; daily; 13 days
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Result:Dose-dependently reduced pulmonary bioluminescence and the number of pulmonary metastatic nodules.
Increased continuous peritumoral collagen deposition, reduced collagen degradation, produced a clearer tumor-stroma interface and better preserved adjacent pulmonary architecture.
化学情報
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CAS 番号 486440-74-8
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分子量 440.12
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分子式 C18H13BrCl2N2O2
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SMILES
O=C(OC(C1=CC=C(Cl)C=C1Cl)CN2C=CN=C2)C3=CC=C(Br)C=C3
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
UE01 関連分類
HY-184501 関連分類
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