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)).
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研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 分子式: C42H50ClF2N11O3
- 分子量:830.37
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保管条件:
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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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
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Aurora A 20 nM (IC50) |
Aurora A 1 nM (Ki) |
Aurora B 7644 nM (Ki) |
Cereblon 4060 nM () |
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.
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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.
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
化学情報
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分子量 830.37
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分子式 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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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
SK4454 関連分類
HY-179640 関連分類
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