BARASERTIB

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C26H31FN7O6P
Molecular Weight	587.5398
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN(CCCOC1=CC=C2C(NC3=CC(CC(=O)NC4=CC=CC(F)=C4)=NN3)=NC=NC2=C1)CCOP(O)(O)=O

InChI

InChIKey=GBJVVSCPOBPEIT-UHFFFAOYSA-N

InChI=1S/C26H31FN7O6P/c1-2-34(10-12-40-41(36,37)38)9-4-11-39-21-7-8-22-23(16-21)28-17-29-26(22)31-24-14-20(32-33-24)15-25(35)30-19-6-3-5-18(27)13-19/h3,5-8,13-14,16-17H,2,4,9-12,15H2,1H3,(H,30,35)(H2,36,37,38)(H2,28,29,31,32,33)

HIDE SMILES / InChI

Molecular Formula	C26H31FN7O6P
Molecular Weight	587.5398
Charge	0
Count

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

Description
Sources: https://openinnovation.astrazeneca.com/barasertib-azd1152.html
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27496133 http://adisinsight.springer.com/drugs/800024339

Barasertib (AZD1152) is a dihydrogen phosphate prodrug of a pyrazoloquinazoline Aurora kinase inhibitor [AZD1152–hydroxyquinazoline pyrazol anilide (HQPA)] and is converted rapidly to the active AZD1152-HQPA in plasma. AstraZeneca was developing the aurora kinase inhibitor, barasertib (AZD 1152) as a therapeutic for cancer. AZD1152-HQPA is a highly potent and selective inhibitor of Aurora B (Ki, 0.36nmol/L) compared with Aurora A (Ki, 1,369nmol/L) and has a high specificity versus a panel of 50 other kinases. Consistent with inhibition of Aurora B kinase, addition of AZD1152-HQPA to tumour cells in vitro induces chromosome misalignment, prevents cell division, and consequently reduces cell viability and induces apoptosis. Barasertib (AZD1152) potently inhibited the growth of human colon, lung, and haematologic tumour xenografts (mean tumour growth inhibition range, 55% to ≥100%; P < 0.05) in immunodeficient mice. Detailed pharmacodynamic analysis in colorectal SW620 tumour-bearing athymic rats treated i.v. with Barasertib (AZD1152) revealed a temporal sequence of phenotypic events in tumours: transient suppression of histone H3 phosphorylation followed by accumulation of 4N DNA in cells (2.4-fold higher compared with controls) and then an increased proportion of polyploid cells (>4N DNA, 2.3-fold higher compared with controls). Histologic analysis showed aberrant cell division that was concurrent with an increase in apoptosis in AZD1152-treated tumours. Bone marrow analyses revealed transient myelosuppression with the drug that was fully reversible following cessation of Barasertib (AZD1152) treatment. Barasertib (AZD1152) was in phase III for the treatment of Acute myeloid leukaemia, but later these studies were discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine/threonine-protein kinase Aurora-B 28 Target ID: CHEMBL2185 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=20420387 \| https://www.ncbi.nlm.nih.gov/pubmed/17495131	Inhibitor 8504		0.37 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Lymphoma 60 Sources: https://clinicaltrials.gov/ct2/show/NCT01354392	Primary		Phase II 1147	Unknown Approved Use Unknown
Acute myeloid leukemia 141 Sources: https://clinicaltrials.gov/ct2/show/NCT00952588	Primary		Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
74.2 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21565405	1200 mg 1 times / day steady-state, intravenous dose: 1200 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered:		BARASERTIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1484 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22661287	220 mg 1 times / day steady-state, intravenous dose: 220 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered:		BARASERTIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
9470 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21565405	1200 mg 1 times / day steady-state, intravenous dose: 1200 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered:		BARASERTIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4054 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22661287	220 mg 1 times / day steady-state, intravenous dose: 220 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered:		BARASERTIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.16 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22661287	220 mg 1 times / day steady-state, intravenous dose: 220 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered:		BARASERTIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
300 mg 1 times / day multiple, intravenous Highest studied dose Dose: 300 mg, 1 times / day Route: intravenous Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22661287	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22661287	DLT: Neutropenia... Disc. AE: Proteinuria... Dose limiting toxicities: Neutropenia (grade 4, 20%) AEs leading to discontinuation/dose reduction: Proteinuria (grade 3, 20%) Sources: https://pubmed.ncbi.nlm.nih.gov/22661287
1200 mg 1 times / day multiple, intravenous MTD Dose: 1200 mg, 1 times / day Route: intravenous Route: multiple Dose: 1200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21976672	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21976672	DLT: Mucositis oral... Disc. AE: Pseudomonal sepsis, cellulitis... Dose limiting toxicities: Mucositis oral (grade 3-4, 16.7%) AEs leading to discontinuation/dose reduction: Pseudomonal sepsis (16.7%) cellulitis (16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/21976672
150 mg 1 times / day multiple, intravenous MTD Dose: 150 mg, 1 times / day Route: intravenous Route: multiple Dose: 150 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22661287	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22661287	Sources: https://pubmed.ncbi.nlm.nih.gov/22661287
220 mg 1 times / day multiple, intravenous MTD Dose: 220 mg, 1 times / day Route: intravenous Route: multiple Dose: 220 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22661287	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22661287	Sources: https://pubmed.ncbi.nlm.nih.gov/22661287
1600 mg 1 times / day multiple, intravenous Studied dose Dose: 1600 mg, 1 times / day Route: intravenous Route: multiple Dose: 1600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21976672	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21976672	DLT: Mucositis oral... Dose limiting toxicities: Mucositis oral (grade 3-4, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/21976672
225 mg 1 times / day multiple, intravenous Studied dose Dose: 225 mg, 1 times / day Route: intravenous Route: multiple Dose: 225 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22661287	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22661287	DLT: Neutropenia, Febrile neutropenia... Dose limiting toxicities: Neutropenia (grade 4, 25%) Febrile neutropenia (grade 4, 25%) Sources: https://pubmed.ncbi.nlm.nih.gov/22661287

AEs

AE	Significance	Dose	Population
Proteinuria	grade 3, 20% Disc. AE	300 mg 1 times / day multiple, intravenous Highest studied dose Dose: 300 mg, 1 times / day Route: intravenous Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22661287	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22661287
Neutropenia	grade 4, 20% DLT	300 mg 1 times / day multiple, intravenous Highest studied dose Dose: 300 mg, 1 times / day Route: intravenous Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22661287	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22661287
Pseudomonal sepsis	16.7% Disc. AE	1200 mg 1 times / day multiple, intravenous MTD Dose: 1200 mg, 1 times / day Route: intravenous Route: multiple Dose: 1200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21976672	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21976672
cellulitis	16.7% Disc. AE	1200 mg 1 times / day multiple, intravenous MTD Dose: 1200 mg, 1 times / day Route: intravenous Route: multiple Dose: 1200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21976672	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21976672
Mucositis oral	grade 3-4, 16.7% DLT	1200 mg 1 times / day multiple, intravenous MTD Dose: 1200 mg, 1 times / day Route: intravenous Route: multiple Dose: 1200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21976672	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21976672
Mucositis oral	grade 3-4, 33.3% DLT, Disc. AE	1600 mg 1 times / day multiple, intravenous Studied dose Dose: 1600 mg, 1 times / day Route: intravenous Route: multiple Dose: 1600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21976672	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21976672
Febrile neutropenia	grade 4, 25% DLT	225 mg 1 times / day multiple, intravenous Studied dose Dose: 225 mg, 1 times / day Route: intravenous Route: multiple Dose: 225 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22661287	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22661287
Neutropenia	grade 4, 25% DLT	225 mg 1 times / day multiple, intravenous Studied dose Dose: 225 mg, 1 times / day Route: intravenous Route: multiple Dose: 225 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22661287	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22661287

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 910 P-gp 1741	BCRP 697 MRP2 252 P-gp 2052

Drug as perpetrator

Target	Modality	Activity	Metabolite
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/21679421/	no	BARASERTIB-hQPA 3
BCRP 985	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23315030/	yes
BCRP 985	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23315030/	yes	BARASERTIB-hQPA 3

Drug as victim

Target	Modality	Activity	Metabolite
MRP2 252	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23315030/	no
MRP2 252	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23315030/	no	BARASERTIB-hQPA 3
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23315030/	yes
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23315030/	yes	BARASERTIB-hQPA 3
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23315030/	yes
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23315030/	yes	BARASERTIB-hQPA 3

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00FCG0	https://www.1pchem.com/search?query=1P00FCG0
AbovChem LLC	AC050732	http://www.abovchem.com/pc/en/product_list.aspx?wd=AC050732
AK Scientific	SYN5717	https://aksci.com/item_detail.php?cat=SYN5717
AOBIOUS INC	AOB87338	http://aobious.com/aobious/search?search_query=AOB87338
ApexBio Technology	A3214	https://www.apexbt.com/catalogsearch/result/?q=A3214
AstaTech	83480	http://astatechinc.com/CPSResult.php?CRNO=83480
BLD Pharm	BD263294	http://www.bldpharm.com/search/Search.html?keyword=BD263294
BOC Sciences	722543-31-9	http://www.bocsci.com/description.asp?cas=722543-31-9
Capot Chemical	16656	https://www.capotchem.com/search.do?q=16656
Cayman Chemical	13647	http://www.caymanchem.com/app/template/Product.vm/catalog/13647
Chem Scene	CS-0978	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0978
Combi-Blocks	QK-7690	http://www.combi-blocks.com/cgi-bin/find.cgi?QK-7690
Debye Scientific	DB-074538	https://www.debyesci.com/index.php?id=product&ext[cno]=DB-074538
eMolecules	31229305	https://orderbb.emolecules.com/search/#?query=31229305
eMolecules	49837439	https://orderbb.emolecules.com/search/#?query=49837439
eMolecules	76743560	https://orderbb.emolecules.com/search/#?query=76743560
KeyOrganics	AS-17018	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-17018
mcule	MCULE-4303553405	https://mcule.com/MCULE-4303553405/
mcule	MCULE-4958215865	https://mcule.com/MCULE-4958215865/
MedChem Express	HY-10127	https://www.medchemexpress.com/search.html?q=HY-10127&ft=&fa=&fp=
Molnova	M15764	https://www.molnova.com/en/serch-list.html?keywords=M15764
MolPort	MolPort-016-631-864	https://www.molport.com/shop/molecule-link/MolPort-016-631-864
MolPort	MolPort-044-561-175	https://www.molport.com/shop/molecule-link/MolPort-044-561-175
ShangHai Biochempartner	BCP13793	http://www.biochempartner.com/search_BCP13793
Toronto Research Chemicals	E679550	https://www.trc-canada.com/product-detail/?CatNum=E679550

PubMed

Title	Date	PubMed
Phase I study of barasertib (AZD1152), a selective inhibitor of Aurora B kinase, in patients with advanced solid tumors.	2013-04	22661287
Phthalazinone pyrazoles as potent, selective, and orally bioavailable inhibitors of Aurora-A kinase.	2011-01-13	21128645
Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines.	2010-12-01	20935223
Aurora kinase inhibitor AZD1152 negatively affects the growth and survival of HTLV-1-infected T lymphocytes in vitro.	2010-10-01	20091867
Aurora kinase inhibitors as anti-cancer therapy.	2010-04	20016367
Antineoplastic effects of an Aurora B kinase inhibitor in breast cancer.	2010-02-22	20175926
The selective Aurora B kinase inhibitor AZD1152 as a novel treatment for hepatocellular carcinoma.	2010-01	19913935
Simultaneous determination of AZD1152 (prodrug) and AZD1152-hydroxyquinazoline pyrazol anilide by reversed phase liquid chromatography.	2009-11-01	19744901
The aurora B kinase inhibitor AZD1152 sensitizes cancer cells to fractionated irradiation and induces mitotic catastrophe.	2009-10-01	19755861
Pharmacological inhibition of aurora-A but not aurora-B impairs interphase microtubule dynamics.	2009-06-01	19395863
Mitotic drivers--inhibitors of the Aurora B Kinase.	2009-06	19189202
AZD1152 rapidly and negatively affects the growth and survival of human acute myeloid leukemia cells in vitro and in vivo.	2009-05-15	19366807
Biochemical characterization of GSK1070916, a potent and selective inhibitor of Aurora B and Aurora C kinases with an extremely long residence time1.	2009-05-13	19284385
Identification of genes that confer tumor cell resistance to the aurora B kinase inhibitor, AZD1152.	2009-04	19188929
The topoisomerase I poison CPT-11 enhances the effect of the aurora B kinase inhibitor AZD1152 both in vitro and in vivo.	2009-03-15	19276280
Enhancement of radiation response in p53-deficient cancer cells by the Aurora-B kinase inhibitor AZD1152.	2008-05-22	18084327
Effects of the aurora kinase inhibitors AZD1152-HQPA and ZM447439 on growth arrest and polyploidy in acute myeloid leukemia cell lines and primary blasts.	2008-05	18367484
Preclinical evaluation of M30 and M65 ELISAs as biomarkers of drug induced tumor cell death and antitumor activity.	2008-03	18347133
The selective Aurora B kinase inhibitor AZD1152 is a potential new treatment for multiple myeloma.	2008-02	18076711
AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivo.	2007-09-15	17495131
AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosis.	2007-06-15	17575233
Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinase.	2007-05-03	17373783
Aurora kinases: new targets for cancer therapy.	2006-12-01	17145803
Aurora kinases: shining lights on the therapeutic horizon?	2005-07-28	16049526
Aurora-kinase inhibitors as anticancer agents.	2004-12	15573114

Patents

Sample Use Guides

In Vivo Use Guide

Up to 6 cycles. Each cycle consists of 800 mg. IV infusion over 96 hrs.

Route of Administration: Intravenous

In Vitro Use Guide

Barasertib inhibited the proliferation of AML lines (HL-60, NB4, MOLM13), ALL line (PALL-2), biphenotypic leukemia (MV4-11), acute eosinophilic leukemia (EOL-1), and the blast crisis of chronic myeloid leukemia K562 cells with an IC50 ranging from 3 nM to 40 nM, as measured by thymidine uptake on day 2 of culture.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:36:11 GMT 2025` Edited by `admin` on `Mon Mar 31 18:36:11 GMT 2025`
Record UNII	16XC2U7W8N
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AZD-1152

Preferred Name

English

BARASERTIB

Official Name

English

AZD1152

Code

English

Barasertib [WHO-DD]

Common Name

English

barasertib [INN]

Common Name

English

1H-PYRAZOLE-3-ACETAMIDE, 5-((7-(3-(ETHYL(2-(PHOSPHONOOXY)ETHYL)AMINO)PROPOXY)-4-QUINAZOLINYL)AMINO)-N-(3-FLUOROPHENYL)-

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C62556