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.
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
- Purity & Documentation
- References
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Biological Activity
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EML4-ALK |
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.
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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.
| 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 |
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.
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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