SK4454
SK4454 is a selective AURKA PROTAC degrader degrading AURKA with IC50 = 8 nM. MYCN levels in MYCN-amplified neuroblastoma cells and limited by MDR1-mediated efflux. SK4454 efficiently reduced AURKA levels in vivo. SK4454 can be used for neuroblastoma research.
(Pink: Aurora A ligand (HY-179643); Blue: Cereblon ligand (HY-179642); Black: linker (HY-69260)).
For research use only. We do not sell to patients.
- Formula: C42H50ClF2N11O3
- Molecular Weight:830.37
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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
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
Aurora A 20 nM (IC50) |
Aurora A 1 nM (Ki) |
Aurora B 7644 nM (Ki) |
Cereblon 4060 nM () |
In Vitro
SK4454 (0.01-10000 nM, 1-48 h) induces degradation AURKA MYCN in neuroblastoma and benign cell lines HEK293T, RPE), exhibits the high potency in MYCN-amplified cells (IMR-32, NGP, SJNB-8; SK-N-BE(2)-C with DC50s = 6 ,8 ,23 and 270 nM), shows reduced activity in other lines (SK-N-BE(2)-C, SK-N-AS, SJNB-1) with a hook effect, induces MYCN depletion as a secondary delayed consequence of AURKA degradation and requires concomitant engagement of both AURKA and CRBN to exert the degradation effect in MYCN amplified cells IMR-32, NGP, SJNB-8, SK-N-BE(2)-C with GI50s = 8, 14, 53, 1111 nM;in non- amplified cells SK-N-SH, SK-N-AS and SJNB-1 with GI50s = 430, 994, 13437nM;inbenign immortalized cell RPE with GI50s = 221 nM[1].
SK4454 (10-10000 nM, 72 h) effectively inhibits neuroblastoma cells (IMR-32, NGP, SJNB 8 , SKN-SH, SK-N-BE(2)-C and SJNB-1) growth[1].
SK4454 (10-1000 nM, 24-72 h) is limited by MDR1-Mediated Drug Efflux in SKN-SH, SK-N-BE(2)-C, SJNB-1, NGP, SJNB-8, IMR-32B but SK-N-AS (due to the low CRBN expression)[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:IMR-32
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Concentration:500 nM
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Incubation Time:1, 4, 24 and 48 h
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Result:Induced robust AURKA depletion already after 1 h, whereas MYCN co-depletion reached 50% only at 24h postexposure.
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Cell Line:IMR-32, NGP, SJNB 8 , SKN-SH, SK-N-BE(2)-C and SJNB-1
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Concentration:10, 100, 1000 and 10000 nM
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Incubation Time:72 h
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Result:Has The strongest antiproliferative effects with GI50 values below 100 nM consistent with the observed potent AURKA degradation but less in SKN-SH, SK-N-BE(2)-C and SJNB-1.
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Cell Line:SK-N-BE(2)-C, SK-N-BE(2)-C, SK-N-SH, and SJNB-1
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Concentration:100 nM
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Incubation Time:24 h
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Result:Exhibit high expression of multidrug resistance protein 1 (MDR1), encoded by the ABCB1 gene in SK-N-BE(2)-C, SK-N-SH, and SJNB-1.
Exhibits the highest MDR1 expression in our panel, cotreatment with 1 μM Tariquidar (HY-10550) significantly enhanced the AURKA degradation.
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Cell Line:NGP and SK-N-BE(2)-C cells
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Concentration:10, 100 and 1000 nM
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Incubation Time:48 h
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Result:Dose-dependently increased of caspase 3/7 activity.
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Cell Line:NGP, SJNB-8, and SK-N-BE(2)-C
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Concentration:10, 100 and 1000 nM
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Incubation Time:72 h
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Result:Exhibited growth-inhibitory activity comparable to AURKA inhibitor TAS-119, with nearly identical GI 50 values across cell lines.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:IMR-32 cells (1 × 10 7 cells in 0.2 mL volume) induced-female BALB/c nude mice[1]
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Dosage:15 mg/kg
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Administration:i.v., or i.p. once
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Result:Reduced AURKA protein levels in vivo at 4 and 8 h post-treatment after a single IV dose, followed by a return to baseline levels at 24 h but not observed in i.p. group
Chemical Information
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Molecular Weight 830.37
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Formula C42H50ClF2N11O3
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SMILES
O=C(C1(CC2=NC(NC3=NNC(C)=C3)=CC=C2F)CCN(CC1)CC4=C(C(Cl)=CC=C4)F)N5CCC(CC5)CN6CCN(CC6)C7=CC=C(C=N7)N8C(NC(CC8)=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)
SK4454 Related Classifications
HY-179640 Related Classifications
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