For research use only. Not for therapeutic Use.
MLN8237（Cat No.:I000178）, also known as alisertib, is a selective inhibitor of aurora kinase A, an enzyme crucial for proper cell division and mitotic spindle assembly. By inhibiting aurora kinase A, MLN8237 disrupts mitosis, leading to cell cycle arrest and apoptosis in cancer cells, particularly those with aneuploidy or other mitotic abnormalities. It has demonstrated efficacy in preclinical studies and early-phase clinical trials for various cancers, including lymphoma and solid tumors. Ongoing research is focused on its potential as a monotherapy and in combination with other treatments to enhance its therapeutic effectiveness.
| Catalog Number | I000178 |
| CAS Number | 1028486-01-2 |
| Synonyms | 4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid |
| Molecular Formula | C₂₇H₂₀ClFN₄O₄ |
| Purity | ≥95% |
| Target | Aurora Kinase |
| Solubility | DMSO: ≥ 28 mg/mL |
| Storage | 3 years -20C powder |
| IC50 | 1.2 nM (Aurora A) |
| IUPAC Name | 4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid |
| InChI | InChI=1S/C27H20ClFN4O4/c1-36-21-5-3-4-20(29)23(21)25-19-10-15(28)6-8-17(19)24-14(12-30-25)13-31-27(33-24)32-16-7-9-18(26(34)35)22(11-16)37-2/h3-11,13H,12H2,1-2H3,(H,34,35)(H,31,32,33) |
| InChIKey | ZLHFILGSQDJULK-UHFFFAOYSA-N |
| SMILES | COC1=C(C(=CC=C1)F)C2=NCC3=CN=C(N=C3C4=C2C=C(C=C4)Cl)NC5=CC(=C(C=C5)C(=O)O)OC |
| Reference | </br>1:Cisplatin-resistant cancer cells are sensitive to Aurora kinase A inhibition by alisertib. Wang L, Arras J, Katsha A, Hamdan S, Belkhiri A, Ecsedy J, El-Rifai W.Mol Oncol. 2017 Apr 18. doi: 10.1002/1878-0261.12066. [Epub ahead of print] PMID: 28417568 Free Article</br>2:Alisertib induces G<sub>2</sub>/M arrest, apoptosis, and autophagy via PI3K/Akt/mTOR- and p38 MAPK-mediated pathways in human glioblastoma cells. Liu Z, Wang F, Zhou ZW, Xia HC, Wang XY, Yang YX, He ZX, Sun T, Zhou SF.Am J Transl Res. 2017 Mar 15;9(3):845-873. eCollection 2017. PMID: 28386317 Free PMC Article</br>3:A phase 2 trial of alisertib in patients with relapsed or refractory B-cellnon-Hodgkin lymphoma. Cohen JB, Maddocks KJ, Huang Y, Christian BA, Jaglowski SM, Flowers CR, Blum KA.Leuk Lymphoma. 2017 Feb 20:1-2. doi: 10.1080/10428194.2017.1289527. [Epub ahead of print] No abstract available. PMID: 28278718 </br>4:A Phase I/II Study of the Investigational Drug Alisertib in Combination With Abiraterone and Prednisone for Patients With Metastatic Castration-Resistant Prostate Cancer Progressing on Abiraterone. Lin J, Patel SA, Sama AR, Hoffman-Censits JH, Kennedy B, Kilpatrick D, Ye Z, Yang H, Mu Z, Leiby B, Lewis N, Cristofanilli M, Kelly WK.Oncologist. 2016 Nov;21(11):1296-1297e. doi: 10.1634/theoncologist.2016-0297. Epub 2016 Oct 24. PMID: 28178640 Free PMC Article</br>5:Association of an aurora kinase a (AURKA) gene polymorphism with progression-free survival in patients with advanced urothelial carcinoma treated with the selective aurora kinase a inhibitor alisertib. Necchi A, Pintarelli G, Raggi D, Giannatempo P, Colombo F.Invest New Drugs. 2017 Feb 3. doi: 10.1007/s10637-017-0440-5. [Epub ahead of print] PMID: 28155045 </br>6:A phase 2 study of alisertib (MLN8237) in recurrent or persistent uterine leiomyosarcoma: An NRG Oncology/Gynecologic Oncology Group study 0231D. Hyman DM, Sill MW, Lankes HA, Piekarz R, Shahin MS, Ridgway MR, Backes F, Tenney ME, Mathews CA, Hoffman JS, Aghajanian C, Hensley ML.Gynecol Oncol. 2017 Jan;144(1):96-100. doi: 10.1016/j.ygyno.2016.10.036. Epub 2016 Oct 27. PMID: 28094040 </br>7:Phase I study of the aurora A kinase inhibitor alisertib with induction chemotherapy in patients with acute myeloid leukemia. Fathi AT, Wander SA, Blonquist TM, Brunner AM, Amrein PC, Supko J, Hermance NM, Manning AL, Sadrzadeh H, Ballen KK, Attar EC, Graubert TA, Hobbs G, Joseph C, Perry AM, Burke M, Silver R, Foster J, Bergeron M, Ramos AY, Som TT, Fishman KM, McGregor KL, Connolly C, Neuberg DS, Chen YB.Haematologica. 2017 Apr;102(4):719-727. doi: 10.3324/haematol.2016.158394. Epub 2016 Dec 29. PMID: 28034990 Free Article</br>8:Alisertib demonstrates significant antitumor activity in bevacizumab resistant, patient derived orthotopic models of glioblastoma. Kurokawa C, Geekiyanage H, Allen C, Iankov I, Schroeder M, Carlson B, Bakken K, Sarkaria J, Ecsedy JA, D/’Assoro A, Friday B, Galanis E.J Neurooncol. 2017 Jan;131(1):41-48. doi: 10.1007/s11060-016-2285-8. Epub 2016 Nov 5. PMID: 27816996 </br>9:Phase II study of MLN8237 (Alisertib) in advanced/metastatic sarcoma. Dickson MA, Mahoney MR, Tap WD, D/’Angelo SP, Keohan ML, Van Tine BA, Agulnik M, Horvath LE, Nair JS, Schwartz GK.Ann Oncol. 2016 Oct;27(10):1855-60. doi: 10.1093/annonc/mdw281. Epub 2016 Aug 8. PMID: 27502708 </br>10:First Multicenter, Randomized Phase 3 Study in Patients (Pts) With Relapsed/Refractory (R/R) Peripheral T-Cell Lymphoma (PTCL): Alisertib (MLN8237) Versus Investigator’s Choice (LUMIERE trial; NCT01482962). [No authors listed]Clin Adv Hematol Oncol. 2016 Feb;14(2 Suppl 1):12-3. No abstract available. PMID: 27466629 |
