alisertib
{{Short description|Selective aurora A kinase inhibitor}}
{{Chembox
| Name =
| ImageFile = Alisertib.svg
| PIN = 4-{[9-Chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoic acid
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|Section1={{Chembox Identifiers
| IUPHAR_ligand = 7790
| Abbreviations =
| CASNo = 1028486-01-2
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| PubChem = 24771867
| ChemSpiderID = 24700147
| 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
| InChI = 1/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-UHFFFAOYAB
| StdInChI = 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)
| StdInChIKey = ZLHFILGSQDJULK-UHFFFAOYSA-N
| RTECS =
| MeSHName =
| ChEBI = 125628
| ChEMBL = 483158
| UNII = T66ES73M18
| KEGG = D10085
}}
|Section2={{Chembox Properties
| C=27 | H=20 | Cl=1 | F=1 | N=4 | O=4
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|Section3={{Chembox Structure
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|Section4={{Chembox Thermochemistry
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|Section5={{Chembox Pharmacology
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|Section6={{Chembox Explosive
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|Section7={{Chembox Hazards
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|Section8={{Chembox Related
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Alisertib (MLN8237) is an orally available , investigational, reversible, ATP-competitive, selective aurora A kinase inhibitor developed by Takeda.{{cite journal|last1=Friedberg|first1=JW|last2=Mahadevan |first2=D |last3=Cebula |first3=E |last4=Persky |first4=D |last5=Lossos |first5=I |last6=Agarwal |first6=AB |last7=Jung |first7=J |last8=Burack |first8=R |last9=Zhou |first9=X |last10=Leonard |first10=EJ |last11=Fingert |first11=H |last12=Danaee |first12=H |last13=Bernstein |first13=SH|title=Phase II study of alisertib, a selective Aurora A kinase inhibitor, in relapsed and refractory aggressive B- and T-cell non-Hodgkin lymphomas.|journal=Journal of Clinical Oncology|date=Jan 1, 2014|volume=32|issue=1|pages=44–50|pmid=24043741|doi=10.1200/JCO.2012.46.8793|pmc=3867644}} Inhibition of aurora A kinase A leads to disruption of mitotic spindle apparatus assembly, disruption of chromosome segregation, and inhibition of cell proliferation.{{Cite journal |last1=Manfredi |first1=Mark G. |last2=Ecsedy |first2=Jeffrey A. |last3=Chakravarty |first3=Arijit |last4=Silverman |first4=Lee |last5=Zhang |first5=Mengkun |last6=Hoar |first6=Kara M. |last7=Stroud |first7=Stephen G. |last8=Chen |first8=Wei |last9=Shinde |first9=Vaishali |last10=Huck |first10=Jessica J. |last11=Wysong |first11=Deborah R. |last12=Janowick |first12=David A. |last13=Hyer |first13=Marc L. |last14=Leroy |first14=Patrick J. |last15=Gershman |first15=Rachel E. |date=2011-12-15 |title=Characterization of Alisertib (MLN8237), an investigational small-molecule inhibitor of aurora A kinase using novel in vivo pharmacodynamic assays |url=https://pubmed.ncbi.nlm.nih.gov/22016509/ |journal=Clinical Cancer Research|volume=17 |issue=24 |pages=7614–7624 |doi=10.1158/1078-0432.CCR-11-1536 |issn=1557-3265 |pmid=22016509}}{{Cite journal |last1=Niu |first1=Huifeng |last2=Manfredi |first2=Mark |last3=Ecsedy |first3=Jeffrey A. |date=2015-08-24 |title=Scientific Rationale Supporting the Clinical Development Strategy for the Investigational Aurora A Kinase Inhibitor Alisertib in Cancer |journal=Frontiers in Oncology |volume=5 |pages=189 |doi=10.3389/fonc.2015.00189 |doi-access=free |issn=2234-943X |pmc=4547019 |pmid=26380220}}
Takeda investigated alisertib as a treatment for relapsed or refractory peripheral T-cell lymphoma{{cite web|title=Millennium Initiates Pivotal Phase 3 Trial of MLN8237 in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma|url=http://www.takeda.com/news/2012/20120306_3946.html|publisher=Takeda Pharmaceutical Company Limited; Millennium Pharmaceuticals, Inc.|accessdate=20 March 2014|date=March 6, 2012}}{{cite web|title=Research and Development Pipeline (As of February 5, 2014)|url=http://www.takeda.com/research/files/pipeline_20140205_en.pdf|publisher=Takeda Pharmaceutical Company Limited|accessdate=20 March 2014|page=2|date=February 5, 2014}} and development was paused in 2015{{Cite web|url=https://www.takeda.com/newsroom/newsreleases/2015/takeda-announces-termination-of-alisertib-phase-3-trial-in-relapsed-or-refractory-peripheral-t-cell-lymphoma/|title=Takeda Announces Termination of Alisertib Phase 3 Trial in Relapsed or Refractory Peripheral T-cell Lymphoma}} until Puma Biotechnology licensed global rights to alisertib from Takeda in 2022.{{Cite news |last=Taylor |first=Nick Paul |date=September 21, 2022 |title=Puma pounces on failed Takeda drug, snapping up cancer prospect for knockdown price |url=https://www.fiercebiotech.com/biotech/puma-pounces-failed-takeda-drug-snapping-cancer-prospect-knockdown-price}}{{Cite news |last=Taylor |first=Phil |date=September 21, 2022 |title=Takeda farms out cancer drug alisertib to Puma Biotech |url=https://pharmaphorum.com/news/takeda-farms-out-cancer-drug-alisertib-to-puma-biotech}}
In clinical trials to date, alisertib has shown single agent activity and activity in combination with other cancer drugs in the treatment of many different types of cancers, including hormone receptor positive breast cancer, triple negative breast cancer, small cell lung cancer and head and neck cancer.{{Cite journal |last=Melichar |first=Bohuslav |last2=Adenis |first2=Antoine |last3=Lockhart |first3=A. Craig |last4=Bennouna |first4=Jaafar |last5=Dees |first5=E. Claire |last6=Kayaleh |first6=Omar |last7=Obermannova |first7=Radka |last8=DeMichele |first8=Angela |last9=Zatloukal |first9=Petr |last10=Zhang |first10=Bin |last11=Ullmann |first11=Claudio Dansky |last12=Schusterbauer |first12=Claudia |date=April 2015 |title=Safety and activity of alisertib, an investigational aurora kinase A inhibitor, in patients with breast cancer, small-cell lung cancer, non-small-cell lung cancer, head and neck squamous-cell carcinoma, and gastro-oesophageal adenocarcinoma: a five-arm phase 2 study |url=https://pubmed.ncbi.nlm.nih.gov/25728526/ |journal=The Lancet. Oncology |volume=16 |issue=4 |pages=395–405 |doi=10.1016/S1470-2045(15)70051-3 |issn=1474-5488 |pmid=25728526}}