PROTAC EML4-ALK Degrader-2
PROTAC EML4-ALK Degrader-2 is an EML4-ALK PROTAC degrader. PROTAC EML4-ALK Degrader-2 shows potent selective inhibitory activity to ALK with an IC50 of 1.6 nM. PROTAC EML4-ALK exhibits selectivity over IGF1R, INSR, FLT3, and FGFR2. PROTAC EML4-ALK Degrader-2 shows anti-cancer activities both in vitro and vivo. PROTAC EML4-ALK Degrader-2 can be used for non-small cell lung cancer (NSLC), liver lung and cervical cancer research.
(Pink: EML4-ALK ligand (HY-15656); Blue: Cereblon ligand (HY-10984); Black: linker (HY-42776)).
For research use only. We do not sell to patients.
- CAS No.: 2417174-28-6
- Formula: C52H66ClN9O11S
- Molecular Weight:1060.65
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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
- Protocols
- Purity & Documentation
- References
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Biological Activity
Description
IC50 & Target
[1]|
EML4-ALK |
In Vitro
PROTAC EML4-ALK Degrader-2 (compound B3) (72 h) shows do not increase the toxicity to normal cells in normal human liver cell line LO2 and shows anti-proliferation effect in H3122, H2228, H1299. A549 and HeLa cells with IC50s of 0.3, 0.9, 2.84, 1.6 and 1.18 μM, respectively[1].
PROTAC EML4-ALK Degrader-2 (0-50 nM,0-32 h) decreases the cellular levels of ALK fusion proteins in a concentration-and time-dependent manner in H3122 cells[1].
PROTAC EML4-ALK Degrader-2 (10-500 nM) shows high selectivity to ALK, maintaining moderate inhibition activity to IGF1R and INSR, and not induce the degradation of IGF1R and INSR[1].
PROTAC EML4-ALK Degrader-2 is effective against ALK-resistant mutations, with its anti-resistance activity spectrum being limited to BaF3-ALK-L1196M and BaF3-ALK-G1202R cells, exhibiting marginally superior activity to LDK378 in targeting BaF3-ALK-L1196M cells [1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:H3122 cells
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Concentration:0, 1, 5, 10, 20, 50 and 100 nM
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Incubation Time:0, 4, 8, 16, 24 and 32 h
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Result:Degraded ALK in a dose dependent manner for 8 h; effectively degraded ALK at 50 nM for 8 h; degraded all the ALK protein at 200 nM.
Achieved amount (>80%) of EML4-ALK degradation after 16 h treatment at 100 nM.
Not observed maximum degradation of EML4-ALK degradation until 24 h at 100 nM.
Inhibited p-ALK and downregulated the level of p-STAT3 after 24 h at 100 nM.
Induced ALK degradation in a concentration dependent manner after 24 h.
Achieved maximum degradation of EML4-ALK degradation at 50 nM.
Downregulated the level of p-ALK and p-STAT3 in a concentration dependent manner after 24 h.
Parmacokinetics
| Species | Dose | Route | AUCall | AUCinf | T1/2 | CL | Vss |
|---|---|---|---|---|---|---|---|
| Rat[1] | 1 mg/kg | i.v. | 1322 ng·h/mL | 1409 ng·h/mL | 4.09 h | 16.3 mL/min/kg | 1335 mL/kg |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:H3122 cells (5 x 106) induced-female BALB/c nude mice (6-7 weeks) (18-22g) [1]
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Dosage:25, 50 mg/kg
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Administration:o.p., once daily for 15 days
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Result:Observed tumor growth inhibitions (TGIs) of 37% and 48% at dose of 25 mg/kg and 50 mg/kg, respectively.
Did not cause significant weight loss and toxicity.
Chemical Information
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CAS No. 2417174-28-6
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Molecular Weight 1060.65
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Formula C52H66ClN9O11S
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SMILES
O=C1NC(C(CC1)N2C(C3=C(C2=O)C(NCCOCCOCCOCCNC(CCN4CCC(CC4)C5=CC(OC(C)C)=C(NC6=NC=C(C(NC7=C(S(=O)(C(C)C)=O)C=CC=C7)=N6)Cl)C=C5C)=O)=CC=C3)=O)=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.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PROTAC EML4-ALK Degrader-2 Related Classifications
HY-180972 Related Classifications
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