ALISERTIB SODIUM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C27H19ClFN4O4.Na.H2O
Molecular Weight	558.921
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.[Na+].COC1=CC(NC2=NC=C3CN=C(C4=CC(Cl)=CC=C4C3=N2)C5=C(OC)C=CC=C5F)=CC=C1C([O-])=O

InChI

InChIKey=WLPXWQKMVACWII-UHFFFAOYSA-M

InChI=1S/C27H20ClFN4O4.Na.H2O/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);;1H2/q;+1;/p-1

HIDE SMILES / InChI

Molecular Formula	C27H20ClFN4O4
Molecular Weight	518.924
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	HO
Molecular Weight	17.0073
Charge	-1
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	Na
Molecular Weight	22.9898
Charge	1
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22016509
Curator's Comment: Description was created based on several sources, including https://www.takeda.com/news/2012/20120306_3946.html http://adisinsight.springer.com/drugs/800025209

Alisertib (MLN8237) is an orally available selective aurora A kinase inhibitor developed by Takeda. Alisertib inhibited AAK over ABK with a selectivity of more than 200-fold in cells and produced a dose-dependent decrease in bipolar and aligned chromosomes in the HCT-116 xenograft model, a phenotype consistent with AAK inhibition. Alisertib inhibited proliferation of human tumor cell lines in vitro and produced tumor growth inhibition in solid tumor xenograft models and regressions in in vivo lymphoma models. It is currently in phase II clinical trials for acute myeloid leukaemia; B cell lymphoma; brain cancer; mesothelioma; prostate cancer; small cell lung cancer.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serine/threonine-protein kinase Aurora-A 37 Target ID: CHEMBL4722 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20382844 \| https://www.ncbi.nlm.nih.gov/pubmed/22016509	Inhibitor 8297	1.2 nM [IC50]
CAL-62 3 Target ID: CHEMBL1075413 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25074669	Inhibitor 8297	76.7 nM [IC50]
NCI-H460 5 Target ID: CHEMBL396 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22016509	Inhibitor 8297	16.0 nM [IC50]
PC-3 15 Target ID: CHEMBL390 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22016509	Inhibitor 8297	54.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Prostate cancer 178 Sources: https://clinicaltrials.gov/ct2/show/NCT01799278	Primary	Phase II 1132	Unknown Approved Use Unknown
Mesothelioma 4 Sources: https://clinicaltrials.gov/ct2/show/NCT02293005	Primary	Phase II 1132	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://clinicaltrials.gov/ct2/show/NCT02187991	Primary	Phase II 1132	Unknown Approved Use Unknown
Acute myelogenous leukemia 19 Sources: https://clinicaltrials.gov/ct2/show/NCT00830518	Primary	Phase II 1132	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: https://clinicaltrials.gov/ct2/show/NCT00853307	Primary	Phase II 1132	Unknown Approved Use Unknown
Small-cell lung cancer 41 Sources: https://clinicaltrials.gov/ct2/show/NCT02038647	Primary	Phase II 1132	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY114921	https://www.001chemical.com/chem/search?q=DY114921
1PlusChem LLC	1P0038TQ	https://www.1pchem.com/search?query=1P0038TQ
A2B Chem	AB50606	http://a2bchem.com/prod/AB50606
AChemBlock	L21796	http://www.achemblock.com/catalogsearch/result/?q=L21796
AK Scientific	SYN5702	https://aksci.com/item_detail.php?cat=SYN5702
AK Scientific	X7389	https://aksci.com/item_detail.php?cat=X7389
AOBIOUS INC	AOB87191	http://aobious.com/aobious/search?search_query=AOB87191
Ambeed	A102516	http://www.ambeed.com/search/Search.html?keyword=A102516
Angene	AGN-PC-0ORXAX	http://www.angenechemical.com/productshow/AGN-PC-0ORXAX.html
ApexBio Technology	A4110	https://www.apexbt.com/catalogsearch/result/?q=A4110
AstaTech	42162	http://astatechinc.com/CPSResult.php?CRNO=42162
Axon MedChem	2003	https://www.axonmedchem.com/product/2003
BLD Pharm	BD239256	http://www.bldpharm.com/search/Search.html?keyword=BD239256
BOC Sciences	1028486-01-2	http://www.bocsci.com/description.asp?cas=1028486-01-2
Capot Chemical	22398	https://www.capotchem.com/search.do?q=22398
Cayman Chemical	13602	http://www.caymanchem.com/app/template/Product.vm/catalog/13602
ChemShuttle	124898	https://www.chemshuttle.com/catalogsearch/result/?q=124898
Excenen	EX-A024	http://www.excenen.com/searchresultlist.php?id=EX-A024
Hairui	HR144167	http://www.hairuichem.com/en/product/search.do?q=HR144167
KeyOrganics	AS-17005	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-17005
Matrix Scientific	97249	http://www.matrixscientific.com/097249.html
MedChem Express	HY-10971	https://www.medchemexpress.com/search.html?q=HY-10971&ft=&fa=&fp=
MolPort	MolPort-009-679-457	https://www.molport.com/shop/molecule-link/MolPort-009-679-457
Molcore	MC114921	http://www.molcore.com/CatMC114921.html
Molnova	M10137	https://www.molnova.com/en/serch-list.html?keywords=M10137
MuseChem	I000178	https://www.musechem.com/product/I000178.html
Ryan Scientific	101-93994	https://ryansci.com/products?q=101-93994&list_q=&search_type=exact
Ryan Scientific	AT_7519__HCl_salt	https://ryansci.com/products?q=AT_7519__HCl_salt&list_q=&search_type=exact
ShangHai Biochempartner	BCP000126	http://www.biochempartner.com/search_BCP000126
ShangHai Biochempartner	BCP01823	http://www.biochempartner.com/search_BCP01823
Synovel	SN-0360	http://www.synovellab.com/?s=SN-0360&submit=Search
Synovel	SN-0390	http://www.synovellab.com/?s=SN-0390&submit=Search
TargetMol	T2241	https://www.targetmol.com/search?keyword=T2241
Toronto Research Chemicals	C982915	https://www.trc-canada.com/product-detail/?CatNum=C982915
Toronto Research Chemicals	M425115	https://www.trc-canada.com/product-detail/?CatNum=M425115
eMolecules	31231103	https://orderbb.emolecules.com/search/#?query=31231103
eNovation Chemicals	D210779	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D210779&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-7766123608	https://mcule.com/MCULE-7766123608/

PubMed

Title	Date	PubMed
Discovery and development of aurora kinase inhibitors as anticancer agents.	2009 May 14	19320489
Drug-resistant aurora A mutants for cellular target validation of the small molecule kinase inhibitors MLN8054 and MLN8237.	2010 Jun 18	20426425
Aurora inhibitor MLN8237 in combination with docetaxel enhances apoptosis and anti-tumor activity in mantle cell lymphoma.	2011 Apr 1	21291867
A Cre-conditional MYCN-driven neuroblastoma mouse model as an improved tool for preclinical studies.	2015 Jun	25174395

Patents

Sample Use Guides

In Vivo Use Guide

50 mg twice daily for 7 days repeated every 21 days, administered on an empty stomach with the patient remaining nothing by mouth (NPO), except for water and prescribed medications, for 2 hours before and 1 hour after each dose, oral dose of Alisertib (MLN8237) should be taken with 8 ounces (1 cup, 240 mL) of water.

Route of Administration: Oral

In Vitro Use Guide

Alisertib (MLN8237) (0.5 uM) treatment inhibits the phosphorylation of Aurora A in human MM1.S and OPM1 cells, without affecting the Aurora B mediated histone H3 phosphorylation. Alisertib (MLN8237) (0.5 uM) induces 2- to 6-fold increase in G2/M phase in primary MM cells and cell lines, as well as significant apoptosis and senescence, involving the up-regulation of p53, p21 and p27, as well as PARP, caspase 3, and caspase 9 cleavage.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 01:40:32 GMT 2023` Edited by `admin` on `Sat Dec 16 01:40:32 GMT 2023`
Record UNII	T76P158V9D
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

ALISERTIB SODIUM

Official Name

English

MLN8237-004

Code

English

MLN-8237-004

Code

English

Alisertib sodium [WHO-DD]

Common Name

English

BENZOIC ACID, 4-((9-CHLORO-7-(2-FLUORO-6-METHOXYPHENYL)-5H-PYRIMIDO(5,4-D)(2)BENZAZEPIN-2-YL)AMINO)-2-METHOXY-, SODIUM SALT, HYDRATE (1:1:1)

Common Name

English

ALISERTIB SODIUM [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C471