1. Cell Cycle/DNA Damage
    Epigenetics
    Autophagy
  2. Aurora Kinase
    Autophagy

Alisertib (Synonyms: MLN 8237)

Cat. No.: HY-10971 Purity: 99.43%
Handling Instructions

Alisertib (MLN 8237) is a selective Aurora A inhibitor with IC50 of 1.2 nM, and is more selective for Aurora A than Aurora B.

For research use only. We do not sell to patients.
Alisertib Chemical Structure

Alisertib Chemical Structure

CAS No. : 1028486-01-2

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 82 In-stock
5 mg USD 72 In-stock
10 mg USD 120 In-stock
50 mg USD 420 In-stock
100 mg USD 706 In-stock
200 mg USD 1140 In-stock
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Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

Alisertib (MLN 8237) is a selective Aurora A inhibitor with IC50 of 1.2 nM, and is more selective for Aurora A than Aurora B.

IC50 & Target

IC50: 1.2 nM (Aurora A)[3]

In Vitro

Alisertib leads the MM cells to mitotic spindle abnormalities, mitotic accumulation, as well as inhibition of cell proliferation through apoptosis and senescence. Alisertib up-regulates p53 and tumor suppressor genes p21 and p27[1]. The decreased activity of MLN8054/Alisertib for the T217D/W277E Aurora A/TPX2 complex may reflect the increased affinity for ATP induced by cofactor binding to Aurora A[2]. Alisertib inhibits cell proliferation with IC50 values ranging from 15 to 469 nM in different tumer cell lines[3].

In Vivo

Alisertib (Alisertib, 30 mg/kg, p.o.) significantly reduces tumor burden and increases overall survival in xenograft-murine model of human-MM[1]. Alisertib (20, 30 mg/kg, p.o.) causes tumor growth inhibition in solid tumor xenograft models and regressions in in vivo models of lymphoma, and reduces FLT uptake in HCT-116 xenograft tumors[3].

Clinical Trial
References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 1.9271 mL 9.6354 mL 19.2708 mL
5 mM 0.3854 mL 1.9271 mL 3.8542 mL
10 mM 0.1927 mL 0.9635 mL 1.9271 mL
Please refer to the solubility information to select the appropriate solvent.
Kinase Assay
[2]

To measure Aurora A activity, 25 ng (12.5 mM final concentration) or 250 ng (125 nM final concentration) of purified bacterially expressed Aurora A is assayed in the presence of the appropriate inhibitors (MLN8054, Alisertib), using Histone H3 as substrate for 20 min at 30°C in the presence of 100 μM [γ-32P] ATP. For Aurora A/TPX2 assays, 50 ng of a TPX2 [1-43] peptide, representing a 2-fold molar excess over Aurora A, is included. The Aurora A/TPX2 complex is preformed in kinase reactions prior to subsequent addition of inhibitors and ATP. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

MLN8237 is dissolved in DMSO.

MM cell lines are incubated with DMSO or Alisertib (0.125-0.5 μM) in combination with conventional anti-MM agents melphalan (2.5-5 μM), doxorubicin (50-100 nM), or dexamethasone (50-100 nM); and with novel anti-MM agents bortezomib (2.5-5 nM) or lenalidomide (0.5-1 μM) for 72 hours. Cell viability is measured by MTT assay. The combination index (CI) is determined by isobologram analysis using CalcuSyn software, Version 2.0 (CI < 1 indicates synergistic effect; CI=1, additive effect; and CI > 1, no significant combination effect). MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

MLN8237 is added to 10% 2-hydroxypropyl-β-cyclodextrin/1% sodium bicarbonate.

Mice are irradiated (200 cGy), and then 5×106 MM1.S cells are inoculated subcutaneously in the right flank. When tumor growth is measurable (2 weeks after the injection), mice are assigned into 4 groups (10 mice each) receiving vehicle orally (100 μL of 10% 2-hydroxypropyl-β-cyclodextrin/1% sodium bicarbonate) or Alisertib (7.5 mg/kg, 15 mg/kg, and 30 mg/kg in a final formulation in 10% 2-hydroxypropyl-β-cyclodextrin/1% sodium bicarbonate) for 21 consecutive days. The maximal tolerated dose of Alisertib in most mouse strains (continuous dosing for 21 days) is approximately 20 mg/kg twice a day (40 mg/kg per day). Tumor volumes are measured by a Vernier caliper every alternate day and calculated using the following formula: length×width2×0.5. Mice are killed at the end of the treatment, 2 hours after the last treatment, or when tumor reaches 2 cm3; tumors are immediately collected from mice and evaluated for induction of apoptosis and cell death by TdT-mediated dUTP nick end labeling (TUNEL) assay. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

518.92

Formula

C₂₇H₂₀ClFN₄O₄

CAS No.

1028486-01-2

SMILES

O=C(C1=CC=C(C=C1OC)NC2=NC=C3CN=C(C4=CC(Cl)=CC=C4C3=N2)C5=C(C=CC=C5F)OC)O

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: 9.33 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 99.43%

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Alisertib
Cat. No.:
HY-10971
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