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Details

Stereochemistry ACHIRAL
Molecular Formula C27H19ClFN4O4.Na
Molecular Weight 540.905
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ALISERTIB SODIUM ANHYDROUS

SMILES

[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=AIUYVPGHBMKGAC-UHFFFAOYSA-M
InChI=1S/C27H20ClFN4O4.Na/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);/q;+1/p-1

HIDE SMILES / InChI

Molecular Formula C27H19ClFN4O4
Molecular Weight 517.916
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
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

Curator's Comment: Alisertib (MLN8237) achieved blood-brain barrier penetration

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1.2 nM [IC50]
Target ID: CHEMBL1075413
76.7 nM [IC50]
16.0 nM [IC50]
54.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Discovery and development of aurora kinase inhibitors as anticancer agents.
2009 May 14
Drug-resistant aurora A mutants for cellular target validation of the small molecule kinase inhibitors MLN8054 and MLN8237.
2010 Jun 18
A novel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and cell-cycle arrest in multiple myeloma.
2010 Jun 24
Patents

Sample Use Guides

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
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 Thu Jul 06 07:45:12 UTC 2023
Edited
by admin
on Thu Jul 06 07:45:12 UTC 2023
Record UNII
23KN826MQ4
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ALISERTIB SODIUM ANHYDROUS
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 (1:1)
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 276309
Created by admin on Thu Jul 06 07:45:12 UTC 2023 , Edited by admin on Thu Jul 06 07:45:12 UTC 2023
Code System Code Type Description
FDA UNII
23KN826MQ4
Created by admin on Thu Jul 06 07:45:12 UTC 2023 , Edited by admin on Thu Jul 06 07:45:12 UTC 2023
PRIMARY
CAS
1028486-06-7
Created by admin on Thu Jul 06 07:45:12 UTC 2023 , Edited by admin on Thu Jul 06 07:45:12 UTC 2023
PRIMARY
PUBCHEM
66819785
Created by admin on Thu Jul 06 07:45:12 UTC 2023 , Edited by admin on Thu Jul 06 07:45:12 UTC 2023
PRIMARY
EPA CompTox
DTXSID40145540
Created by admin on Thu Jul 06 07:45:12 UTC 2023 , Edited by admin on Thu Jul 06 07:45:12 UTC 2023
PRIMARY
SMS_ID
100000178047
Created by admin on Thu Jul 06 07:45:12 UTC 2023 , Edited by admin on Thu Jul 06 07:45:12 UTC 2023
PRIMARY
Related Record Type Details
SOLVATE->ANHYDROUS
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY