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Purity: ≥98%
Alisertib (also named as MLN8237, MLN-8237) is a novel potent, selective, orally bioavailable Aurora A kinase (AAK) inhibitor with potential antitumor activity. It inhibits Aurora A kinase with an IC50 of 1.2 nM in a cell-free assay and exhibits >200-fold higher selectivity for Aurora A than Aurora B. Alisertib shows potent in vitro antiproliferative activity and high in vivo antitumor efficacy. Alisertib was developed from its predecessor, MLN8054, in order to minimize the benzodiazepine-like effects seen with MLN8054. The inhibitory effect of Alisertib is ATP-competitive, reversible and AAK-specific with an inhibition constant (Ki) of 0.43 nmol/L. MLN8237 is being investigated to treat advanced cancers.
| ln Vitro |
Alisertib (MLN 8237) induces aberrant mitotic spindles in MM cells, mitotic accumulation, and senescence and death to prevent cell division. Tumor suppressor genes p21 and p27, as well as p53, are upregulated by aleritetib[1]. The enhanced affinity for ATP brought on by cofactor binding to Aurora A may be the cause of Alisertib's (MLN 8237) lower activity for the T217D/W277E Aurora A/TPX2 complex[2]. In various tumor cell lines, aleretitib (MLN 8237) suppresses cell growth with IC50s ranging from 15 to 469 nM[4].
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| ln Vivo |
In the xenograft-murine model of human-MM, alestertib (MLN 8237) (30 mg/kg, po) dramatically lowers tumor burden and improves overall survival[1]. In solid tumor xenograft models, alisertib (3-30 mg/kg; po; once daily for 3 weeks) inhibits the growth of tumors[4].
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| Animal Protocol |
Animal/Disease Models: Nude mice bearing HCT-116 colon tumor xenograft[4]
Doses: 3, 10, or 30 mg/kg Route of Administration: Po; one time/day for 3 weeks Experimental Results: Resulted in a dose-dependent TGI (tumor growth inhibition) of 43.3%, 84.2%, and 94.7% for the 3, 10, and 30 mg/kg groups, respectively. |
| References |
[1]. Güllü G, et al. A novel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and cell-cycle arrest in multiple myeloma Blood June 24, 2010 vol. 115 no. 25 5202-5213.
[2]. Sloane DA, et al. Drug-Resistant Aurora A Mutants for Cellular Target Validation of the Small Molecule Kinase Inhibitors MLN8054 and MLN8237 ACS Chem. Biol., 2010, 5 (6), pp 563-576. [3]. Bavetsias V, et al. Aurora Kinase Inhibitors: Current Status and Outlook. Front Oncol. 2015 Dec 21;5:278. [4]. Manfredi MG, et al. Characterization of Alisertib (MLN8237), an investigational small-molecule inhibitor of aurora A kinase using novel in vivo pharmacodynamic assays.Clin Cancer Res. 2011 Dec 15;17(24):7614-7624. |
| Molecular Formula |
C27H20CLFN4O4
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|---|---|
| Molecular Weight |
518.92
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| CAS # |
1028486-01-2
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| Related CAS # |
Alisertib sodium;1028486-06-7
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| SMILES |
O=C(O)C1=CC=C(NC2=NC=C3C(C4=CC=C(Cl)C=C4C(C5=C(OC)C=CC=C5F)=NC3)=N2)C=C1OC
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| Chemical Name |
4-((9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-benzo[c]pyrimido[4,5-e]azepin-2-yl)amino)-2-methoxybenzoic acid
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| Synonyms |
MLN-8237; alisertib; MLN8237; MLN 8237
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (4.01 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.08 mg/mL (4.01 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.01 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 15% Captisol:5mg/mL |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT06095505 | Recruiting | Drug: Alisertib | Small Cell Lung Cancer | Puma Biotechnology, Inc. | February 8, 2024 | Phase 2 |
| NCT02812056 | Withdrawn | Drug: Alisertib Drug: TAK-228 |
Malignant Neoplasms of Digestive Organs Malignant Neoplasms of Female Genital Organs |
M.D. Anderson Cancer Center | September 2016 | Phase 1 |
| NCT01898078 | Completed Has Results | Drug: Alisertib | Advanced Solid Tumors Lymphoma |
Millennium Pharmaceuticals, Inc. | July 16, 2013 | Phase 1 |
| NCT02214147 | Completed Has Results | Drug: Alisertib | Advanced Solid Tumors Relapsed/Refractory Lymphoma |
Millennium Pharmaceuticals, Inc. | August 21, 2014 | Phase 1 |
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