MLN8054 SODIUM

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H14ClF2N4O2.Na
Molecular Weight	498.844
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].[O-]C(=O)C1=CC=C(NC2=NC3=C(CN=C(C4=CC(Cl)=CC=C34)C5=C(F)C=CC=C5F)C=N2)C=C1

InChI

InChIKey=CPUPAOAXNTYRQJ-UHFFFAOYSA-M

InChI=1S/C25H15ClF2N4O2.Na/c26-15-6-9-17-18(10-15)23(21-19(27)2-1-3-20(21)28)29-11-14-12-30-25(32-22(14)17)31-16-7-4-13(5-8-16)24(33)34;/h1-10,12H,11H2,(H,33,34)(H,30,31,32);/q;+1/p-1

HIDE SMILES / InChI

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

Molecular Formula	C25H14ClF2N4O2
Molecular Weight	475.854
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/17360485
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20607239

MLN8054 is a reversible, ATP competitive inhibitor of recombinant Aurora A, developed by Millennium Pharmaceuticals. MLN8054 was tested in phase I clinical trials against advanced solid tumors. Reversible somnolence probably due to off-target inhibition of alpha-1 subunit of GABA-A receptor was dose limiting and prevented achievement of plasma concentrations predicted necessary for target modulation.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine/threonine-protein kinase Aurora-A 37 Target ID: CHEMBL4722 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17360485	Inhibitor 8297		4.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20607239	Primary	Phase I 428	Unknown Approved Use Unknown
Colon cancer 62 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20607239	Primary	Phase I 428	Unknown Approved Use Unknown
Pancreatic cancer 97 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20607239	Primary	Phase I 428	Unknown Approved Use Unknown
Bladder cancer 16 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20607239	Primary	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
2129 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20607239	20 mg 4 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MLN8054 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2642 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20607239	15 mg 4 times / day multiple, oral dose: 15 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MLN8054 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
10109 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20607239	20 mg 4 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MLN8054 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
13203 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20607239	15 mg 4 times / day multiple, oral dose: 15 mg route of administration: Oral experiment type: MULTIPLE co-administered:		MLN8054 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P004LPZ	https://www.1pchem.com/search?query=1P004LPZ
AK Scientific	2558AH	https://aksci.com/item_detail.php?cat=2558AH
ApexBio Technology	A4114	https://www.apexbt.com/catalogsearch/result/?q=A4114
BLD Pharm	BD163533	http://www.bldpharm.com/search/Search.html?keyword=BD163533
Chem Scene	CS-0010	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0010
ChemShuttle	141348	https://www.chemshuttle.com/catalogsearch/result/?q=141348
Exclusive Chemistry	2342	http://www.exchemistry.com/chem-catalog/product-2342.html
KeyOrganics	AS-74414	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-74414
MedChem Express	HY-10180	https://www.medchemexpress.com/search.html?q=HY-10180&ft=&fa=&fp=
MolPort	MolPort-016-633-177	https://www.molport.com/shop/molecule-link/MolPort-016-633-177
Molnova	M16315	https://www.molnova.com/en/serch-list.html?keywords=M16315
MuseChem	M143159	https://www.musechem.com/product/M143159.html
MuseChem	R051392	https://www.musechem.com/product/R051392.html
ShangHai Biochempartner	BCP02261	http://www.biochempartner.com/search_BCP02261
TargetMol	T6315	https://www.targetmol.com/search?keyword=T6315
Toronto Research Chemicals	M425125	https://www.trc-canada.com/product-detail/?CatNum=M425125
eMolecules	31231105	https://orderbb.emolecules.com/search/#?query=31231105
eNovation Chemicals	D491488	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D491488&searchbtn.x=0&searchbtn.y=0
eNovation Chemicals	K09720	https://www.enovationchem.com/Products.asp?SEARCHTEXT=K09720&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-8254255695	https://mcule.com/MCULE-8254255695/

PubMed

Title	Date	PubMed
Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase.	2007 Mar 6	17360485
A class of 2,4-bisanilinopyrimidine Aurora A inhibitors with unusually high selectivity against Aurora B.	2009 May 28	19402633
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.	2010 Nov 24	21095574
Phthalazinone pyrazoles as potent, selective, and orally bioavailable inhibitors of Aurora-A kinase.	2011 Jan 13	21128645
Comprehensive analysis of kinase inhibitor selectivity.	2011 Oct 30	22037378

Patents

Sample Use Guides

In Vivo Use Guide

In clinical trials against advanced solid tumors MLN8054 was administered orally in multiple divided daily doses for 7 days to 21 consecutive days. A 14-day recovery period followed each dosing period, regardless of its duration. MLN8054 was supplied in capsules of 5 mg or 25 mg. MLN8054 will be given on an empty stomach. Patients were instructed to take nothing by mouth except for water and prescribed medications for 2 hours before and 1 hour after each dose.

Route of Administration: Oral

In Vitro Use Guide

Recombinant murine Aurora A protein was expressed in Sf9 cells and purified with GST affinity chromatography. The peptide substrate for Aurora A was conjugated with biotin (Biotin-GLRRASLG). Aurora A kinase (5 nM) was assayed in 50 mM Hepes (pH 7.5)/10 mM MgCl2/5 mM DTT/0.05% Tween 20/2 μM peptide substrate/3.3 μCi/ml [γ-33P]ATP at 2 μM by using Image FlashPlates (Perkin–Elmer).

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:55:42 GMT 2023` Edited by `admin` on `Fri Dec 15 15:55:42 GMT 2023`
Record UNII	931G05H22J
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MLN8054 SODIUM

Common Name

English

BENZOIC ACID, 4-((9-CHLORO-7-(2,6-DIFLUOROPHENYL)-5H-PYRIMIDO(5,4-D)(2)BENZAZEPIN-2-YL)AMINO)-, MONOSODIUM SALT

Common Name

English

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

Common Name

English

Code System Code Type Description

CAS

869366-15-4