ALK degrader 1
ALK degrader 1 is a potent, hydrophobic tag (HyT)-based degrader that induces ubiquitin-proteasome system (UPS)-dependent EML4-ALK degradation (DC50 = 0.13 μM). ALK degrader 1 demonstrates potent ALK degradation and antiproliferative effects in ALK-dependent cell lines, while showing minimal cytotoxicity in ALK fusion-negative cells. ALK degrader 1 triggers cell cycle arrest at the G0/G1 phase and stimulates apoptosis. ALK degrader 1 not only facilitates efficient degradation of the ALK protein but also disrupts key downstream effectors, including the STAT3 signaling axis. ALK degrader 1 mediates robust EML4-ALK degradation in vivo. ALK degrader 1 can be used for ALK-related diseases research.
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- Formel: C39H47N5O2
- Molecular Weight:617.82
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
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Chemical Information
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Help & FAQs
Biologische Aktivität
ALK degrader 1 (compound H7) (72 h) shows antiproliferative effects in ALK-dependent cell lines, with an IC50 of 0.23 μM in H3122 cells and an IC50 of 0.19 μM in Karpas 299 cells[1].
ALK degrader 1 (0.5-5 μM, 24 h) effectively degrades EML4-ALK in H3122 cells, achieving over 80% degradation at 0.5 μM, and shows moderately reduced activity against NPM-ALK in Karpas 299 cells, achieving approximately 70 % degradation at 5 μM[1].
ALK degrader 1 (0.1-5 μM, 2-24 h) is a potent EML4-ALK degrader (DC50 = 0.13 μM) with a rapid, sustained degradation profile, effectively suppressing ALK phosphorylation and downstream STAT3 signaling in H3122 cells[1].
ALK degrader 1 (2 μM, 24 h) maintains prolonged EML4-ALK degradation for 48 hours after removal[1].
ALK degrader 1 (0.5-2 μM, 24 h) potently inhibits mitotic progression in H3122 cells, triggering G0/G1 phase arrest and thereby inducing apoptosis[1].
ALK degrader 1 (2 μM, 24 h) upregulates ALK mRNA, induces ALK-Hsp70 binding, and is inhibited by MG-132 (HY-13259), collectively demonstrating that degradation is mediated by the UPS[1].
ALK degrader 1 (0.1-1 μM, 72 h) demonstrates good selectivity against ALK-negative tumor cells (A549) and normal pulmonary epithelial fibroblasts (HFL-1), with no apparent toxic side effects, indicating a favorable safety profile[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:H3122 and Karpas 299 cells
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Concentration:0.5, 1, and 5 μM
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Incubation Time:24 h
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Result:Effectively degraded EML4-ALK in H3122 cells at 5 μM after 24 h.
Exhibited substantial EML4-ALK degradation efficacy even at 0.5 μM, with more than 80 % reduction observed in Karpas 299 cells.
Showed reduced degradation activity against NPM-ALK in Karpas 299 cells compared to its activity against EML4-ALK in H3122 cells.
Demonstrated appreciable NPM-ALK degradation in Karpas 299 cells, achieving approximately 70 % degradation at 5 μM.
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Cell Line:H3122 cells
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Concentration:0.1, 0.5, 1, 2, and 5 μM
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Incubation Time:2, 4, 8, 16, 24 h
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Result:Exhibited a concentration-dependent ability to degrade EML4-ALK in H3122 cells, with complete degradation observed and a DC50 of 0.13 μM.
Significant reduced ALK levels in H3122 cells at 0.5, 1 and 2 μM for 24 h.
Decreased ALK phosphorylation in H3122 cells at 0.1 μM.
Decreased p-STAT3 levels but did not change STAT3 levels in H3122 cells.
(2 μM)Induced effective and sustained degradation of EML4-ALK in H3122 cells, reaching approximately 30 % at 2 h, peaking by 4 h, maintaining suppression to 23 % at 24 h.
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Cell Line:H3122 cells
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Concentration:2 μM
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Incubation Time:24 h
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Result:Maintained low EML4-ALK levels for 48 hours after removal.
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Cell Line:H3122 cells
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Concentration:0.5, 1, and 2 μM
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Incubation Time:24 h
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Result:Significantly increased the G0/G1 phase cell population and reduced the G2 phase population compared to control after 24 h at 2 μM.
Significantly increased the sub-G0 phase cell population.
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Cell Line:H3122 cells
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Concentration:0.5, 1, and 2 μM
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Incubation Time:24 h
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Result:Increased the proportion of apoptotic cells from 9.41 % to 21.07 % after 24 h at 2 μM.
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Cell Line:H3122, HFL-1 and A549 cells.
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Concentration:0.1, 0.5, and 1 μM
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Incubation Time:72 h
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Result:Inhibited H3122 cell proliferation by 30 % at 0.1 μM, while the inhibition rates for A549 and HFL-1 cells were 14 % and 12 %, respectively.
Iinhibited the proliferation of over 80 % of H3122 cells at 0.5 μM, but showed minimal activity against HFL-1 and A549 cells.
Exhibited a 90 % inhibition rate against H3122 cells at 1 μM, while its toxicity toward HFL-1 and A549 cells remained very low.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female BALB/c nude mice (4 weeks old) subcutaneously inoculated with H3122 cells[1]
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Dosage:20 mg/kg
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Administration:i.v., once
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Result:Exhibited sustained EML4-ALK degradation, detectable by 12 hours post-treatment and achieving over 85 % by 36 hours.
Chemical Information
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Molecular Weight 617.82
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Formel C39H47N5O2
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SMILES
O=C(C(C=C(CC)C(N1CCN(CCCC(NC2(C3)C[C@@H](C4)C[C@H]3C[C@@H]4C2)=O)CC1)=C5)=C5C6(C)C)C7=C6NC8=CC(C#N)=CC=C87
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
ALK degrader 1 Related Classifications
HY-175849 Related Classifications
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