2. PROTAC Epigenetics Cell Cycle/DNA Damage
  3. PROTACs Aurora Kinase
  4. 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.

SK4454

SK4454 Chemical Structure

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SK4454 Related Antibodies

Top Publications Citing Use of Products

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von Hippel-Lindau (VHL) Cereblon MDM2 cIAP1

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Aurora Kinase Aurora A Aurora B Aurora C

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Description

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[1]. (Pink: Aurora A ligand (HY-179643); Blue: Cereblon ligand (HY-179642); Black: linker (HY-69260)).

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.

SK4454 Related Antibodies

Western Blot Analysis[1]

Cell Line: IMR-32
Concentration: 500 nM
Incubation Time: 1, 4, 24 and 48 h
Result: Induced robust AURKA depletion already after 1 h, whereas MYCN co-depletion reached 50% only at 24h postexposure.

Cell Proliferation Assay[1]

Cell Line: IMR-32, NGP, SJNB 8 , SKN-SH, SK-N-BE(2)-C and SJNB-1
Concentration: 10, 100, 1000 and 10000 nM
Incubation Time: 72 h
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.

Western Blot Analysis[1]

Cell Line: SK-N-BE(2)-C, SK-N-BE(2)-C, SK-N-SH, and SJNB-1
Concentration: 100 nM
Incubation Time: 24 h
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.

Apoptosis Analysis[1]

Cell Line: NGP and SK-N-BE(2)-C cells
Concentration: 10, 100 and 1000 nM
Incubation Time: 48 h
Result: Dose-dependently increased of caspase 3/7 activity.

Cell Proliferation Assay[1]

Cell Line: NGP, SJNB-8, and SK-N-BE(2)-C
Concentration: 10, 100 and 1000 nM
Incubation Time: 72 h
Result: Exhibited growth-inhibitory activity comparable to AURKA inhibitor TAS-119, with nearly identical GI 50 values across cell lines.
Parmacokinetics
Species Dose Route Cmax F T1/2 Tmax C0 Vss
Mice[1] 15 mg/kg i.p. 856 ng/mL 7 % 5.3 h 0.5 h / /
Mice[1] 15 mg/kg i.v. / / 3.4 h / 11601 ng/mL 3.1 L/kg
Mice[1] 30 mg/kg p.o. 856 ng/mL 7 % 2.5 h 0.5 h / /
In Vivo

SK4454 (15 mg/kg, i.v. or i.p., once) induce AURKA protein depletion in IMR-32 neuroblastoma cell line-derived xenograft (CDX) mice[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: IMR-32 cells (1 × 10 7 cells in 0.2 mL volume) induced-female BALB/c nude mice[1]
Dosage: 15 mg/kg
Administration: i.v., or i.p. once
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
Molecular Weight

830.37

Formula

C42H50ClF2N11O3
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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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SK4454 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

SK4454SK 4454SK-4454PROTACsAurora KinaseAURKANanoLuc-AURKAMYCNMDR1-mediated effluxneuroblastomaInhibitorinhibitorinhibit

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