PROTAC Axl Degrader 1
PROTAC Axl Degrader 1 is an orally active PROTAC degrader targeting the AXL receptor tyrosine kinase, with an IC50 of 0.92 μM against human targets. PROTAC Axl Degrader 1 induces cytoplasmic vacuolization, methuosis (macropinocytosis-induced cell death), excessive macropinosome production, and Rac1 activation. PROTAC Axl Degrader 1 inhibits the proliferation and migration of cancer cells. PROTAC Axl Degrader 1 can be used in breast cancer-related research.
(Pink: Axl ligand (HY-184184); Blue: Cereblon ligand (HY-A0003); Black: linker (HY-W007700)).
For research use only. We do not sell to patients.
- CAS No.: 3033401-47-4
- Formula: C40H43N11O4
- Molecular Weight:741.84
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Storage:
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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Biological Activity
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Chemical Information
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- References
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Biological Activity
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Axl 0.92 μM (IC50) |
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Cell Line
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Type | Value | Description | References |
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| 4T1 | IC50 |
5.53 μM
Compound: 22
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Antiproliferative activity against mouse 4T1 cells highly expressing AXL after 72 hrs by MTT assay
Antiproliferative activity against mouse 4T1 cells highly expressing AXL after 72 hrs by MTT assay
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[PMID: 35279611] |
| GES1 | IC50 |
>60 μM
Compound: 22
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Cytotoxicity against human GES1 cells after 72 hrs by MTT assay
Cytotoxicity against human GES1 cells after 72 hrs by MTT assay
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[PMID: 35279611] |
| MCF-10A | IC50 |
>60 μM
Compound: 22
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Cytotoxicity against human MCF-10A cells after 72 hrs by MTT assay
Cytotoxicity against human MCF-10A cells after 72 hrs by MTT assay
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[PMID: 35279611] |
| MDA-MB-231 | IC50 |
10.34 μM
Compound: 22
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Antiproliferative activity against human MDA-MB-231 cells highly expressing AXL after 72 hrs by MTT assay
Antiproliferative activity against human MDA-MB-231 cells highly expressing AXL after 72 hrs by MTT assay
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[PMID: 35279611] |
PROTAC Axl Degrader 1 (compound 22) inhibits AXL enzymatic activity with an IC50 of 0.92 μM, and exhibits high selectivity for AXL, with an inhibition rate of over 90% at a concentration of 5 μM[1].
PROTAC Axl Degrader 1 (0.0001-100 μM; 30 min) forms a ternary complex with AXL and CRBN proteins, and the amount and potency of ternary complex formation reach a peak at 1 μM[1].
PROTAC Axl Degrader 1 (0.5 μM; 48 h) induces cytoplasmic vacuolization consistent with methuosis (giant vacuole-mediated cell death) in MDA-MB-231 and 4T1 breast cancer cells[1].
PROTAC Axl Degrader 1 (24 h; 2 h) induces endocytic macropinosomes independent of mitochondrial or lysosomal origin in MDA-MB-231 breast cancer cells[1].
PROTAC Axl Degrader 1 induces cytoplasmic vacuolization in MDA-MB-231 breast cancer cells, a process dependent on the Rac1 pathway and independent of caspase-mediated apoptosis[1].
PROTAC Axl Degrader 1 (72 h) inhibits the proliferation of MDA-MB-231 and 4T1 breast cancer cells with IC50 values of 10.34 μM and 5.53 μM, respectively, and shows no significant cytotoxicity against normal MCF-10A and GES-1 cells[1].
PROTAC Axl Degrader 1 (0.5-2 μM; 24-48 h) induces proteasome-dependent degradation of AXL protein in MDA-MB-231 cells[1].
PROTAC Axl Degrader 1 (1-10 μM; 48 h) significantly inhibits the migration of MDA-MB-231 and 4T1 breast cancer cells[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 breast cancer cells
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Concentration:0.5, 2 μM
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Incubation Time:24 h; 48 h
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Result:Induced AXL protein degradation after 24 h of treatment at both 0.5 μM and 2 μM.
Showed a more pronounced decrease in AXL protein levels after 48 h of treatment at both concentrations.
Had its induced AXL protein degradation reversed in the presence of the proteasome inhibitor epoxymycin (EPO).
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Cell Line:MDA-MB-231 breast cancer cells, 4T1 breast cancer cells
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Concentration:1, 10 μM
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Incubation Time:0, 48 h
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Result:Significantly inhibited migration of MDA-MB-231 cells at 0.5 μM, 1 μM, and 2 μM.
Suppressed MDA-MB-231 cell migration to a significantly greater extent than the control compound R428 (HY-15150) at 0.5 μM.
Showed an inhibitory effect on MDA-MB-231 cell migration similar to that of R428 at 2 μM.
Significantly inhibited migration of 4T1 cells at both 0.5 μM and 2 μM.
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 (female, tumor-bearing MDA-MB-231 xenograft, treatment initiated at tumor volume 150 mm3)[1]
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Dosage:25 mg/kg
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Administration:i.p.; daily; 14 days
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Result:Reduced final tumor volume significantly compared to saline control.
Lowered final tumor weight compared to saline control, with an anti-tumor rate of approximately 56%.
Showed no significant differences in body weight between treated and control mice.
Caused no obvious necrosis or inflammatory cell infiltration in tumor and major organs via H&E staining, indicating no systemic toxicity.
Chemical Information
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CAS No. 3033401-47-4
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Molecular Weight 741.84
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Formula C40H43N11O4
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SMILES
NC1=NC(NC2=CC=C(C=C2)CNC(CCCCCCCNC3=CC=CC4=C3CN(C4=O)C5CCC(NC5=O)=O)=O)=NN1C6=CC=C(N=N6)C7=CC=CC=C7
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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)
PROTAC Axl Degrader 1 Related Classifications
HY-144624 Related Classifications
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