Barasertib

Summary

Barasertib (CHEMBL415049) is a phase-3 clinical-stage small-molecule prodrug targeting AURKA and AURKB; indicated across 4 conditions including acute myeloid leukemia and lymphoma.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 2 (AURKA, AURKB)
• Indications: 4 conditions
• Clinical trials: 8
• Chemistry: 587.5 Da · C26H31FN7O6P

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL415049
Name	Barasertib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	11497983
ChEBI	CHEBI:167636
Molecular formula	C26H31FN7O6P
Molecular weight	587.5
InChIKey	GBJVVSCPOBPEIT-UHFFFAOYSA-N

SMILES: CCN(CCCOC1=CC2=C(C=C1)C(=NC=N2)NC3=NNC(=C3)CC(=O)NC4=CC(=CC=C4)F)CCOP(=O)(O)O

IUPAC name: 2-[ethyl-[3-[4-[[5-[2-(3-fluoroanilino)-2-oxoethyl]-1H-pyrazol-3-yl]amino]quinazolin-7-yl]oxypropyl]amino]ethyl dihydrogen phosphate

ChEBI definition: 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.

Pharmacological roles (ChEBI): prodrug, antineoplastic agent, Aurora kinase inhibitor.

Also known as: AZD 1152, Azd-1152, AZD-1152, AZD1152, Barasertib, Barasertib (who-dd), AZD-2811, BARASERTIB (WHO-DD), BARASERTIB, SID103905346, barasertib

Patent coverage: 828 distinct patent families (2,371 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 2,077 (88%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
AURKA	aurora kinase A	Inhibition	5.86	99.4% (common-essential)	O14965
AURKB	aurora kinase B	Inhibition	9.43	99.7% (common-essential)	Q96GD4

Broader ChEMBL bioactivity targets: 21 (assay-derived). Sample: Tyrosine-protein kinase Fyn, Platelet-derived growth factor receptor beta, Mast/stem cell growth factor receptor Kit, Receptor-type tyrosine-protein kinase FLT3, Platelet-derived growth factor receptor alpha, Epidermal growth factor receptor, Proto-oncogene tyrosine-protein kinase receptor Ret, Aurora kinase B, Dual specificity tyrosine-phosphorylation-regulated kinase 1A, Tyrosine-protein kinase Lck.

Bioactivity

ChEMBL activities: 48 potent at pChembl ≥ 5 of 48 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
AURKB	9.45	Ki	0.36	nM	CHEMBL_ACT_26326148
AURKB	9.44	Ki	0.36	nM	CHEMBL_ACT_26326220
AURKB	9.43	Ki	0.37	nM	CHEMBL_ACT_13343476
AURKB	9.43	IC50	0.37	nM	CHEMBL_ACT_16604367
AURKA	9.43	IC50	0.37	nM	CHEMBL_ACT_24359163
AURKB	9.43	IC50	0.37	nM	CHEMBL_ACT_24959158
AURKB	9.43	IC50	0.37	nM	CHEMBL_ACT_29126588
AURKA	8.86	Ki	1.37	nM	CHEMBL_ACT_26326219
AURKB	8.3	Ki	5.01	nM	CHEMBL_ACT_9577743
FLT3	8.1	Kd	8	nM	CHEMBL_ACT_2526366
AURKB	7.99	IC50	10.27	nM	CHEMBL_ACT_26326222
KIT	7.77	Kd	17	nM	CHEMBL_ACT_2526382
AURKC	7.77	Ki	17.03	nM	CHEMBL_ACT_26326151
AURKC	7.77	Ki	17	nM	CHEMBL_ACT_26326221
AURKC	7.77	IC50	17	nM	CHEMBL_ACT_3294182
KIT	7.7	Ki	19.95	nM	CHEMBL_ACT_9578855
RAB6A	7.48	Kd	33	nM	CHEMBL_ACT_17934478
PDGFRA	7.42	Kd	38	nM	CHEMBL_ACT_2526383
AURKA	7.4	Ki	39.81	nM	CHEMBL_ACT_9586092
PDGFRB	7.39	Kd	41	nM	CHEMBL_ACT_2526385
AURKA	7.31	Kd	49	nM	CHEMBL_ACT_17884121
RET	7.1	Kd	80	nM	CHEMBL_ACT_2526378
MAP2K5	7.09	Kd	82	nM	CHEMBL_ACT_17911326
AURKB	6.96	IC50	110.6	nM	CHEMBL_ACT_26329570
RET	6.8	Ki	158.5	nM	CHEMBL_ACT_9541195
RET	6.68	Kd	209	nM	CHEMBL_ACT_17935159
FLT3	6.59	Kd	257	nM	CHEMBL_ACT_17903570
KDR	6.5	Ki	316.2	nM	CHEMBL_ACT_9581026
PDGFRB	6.5	Ki	316.2	nM	CHEMBL_ACT_9591762
AURKB	6.16	IC50	692.8	nM	CHEMBL_ACT_26329289

Target pathways

Aggregated over 2 target gene(s): AURKA, AURKB.

Top Reactome pathways

42 total, by targets touching each:

Pathway	Targets	Genes
Cell Cycle	2	AURKA, AURKB
APC/C-mediated degradation of cell cycle proteins	2	AURKA, AURKB
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1	2	AURKA, AURKB
Generic Transcription Pathway	2	AURKA, AURKB
SUMOylation	2	AURKA, AURKB
SUMO E3 ligases SUMOylate target proteins	2	AURKA, AURKB
Transcriptional Regulation by TP53	2	AURKA, AURKB
Metabolism of proteins	2	AURKA, AURKB
Regulation of mitotic cell cycle	2	AURKA, AURKB
SUMOylation of DNA replication proteins	2	AURKA, AURKB
Regulation of TP53 Activity	2	AURKA, AURKB
Post-translational protein modification	2	AURKA, AURKB
Regulation of TP53 Activity through Phosphorylation	2	AURKA, AURKB
Cell Cycle, Mitotic	2	AURKA, AURKB
RNA Polymerase II Transcription	2	AURKA, AURKB
Gene expression (Transcription)	2	AURKA, AURKB
Amplification of signal from the kinetochores	1	AURKB
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	AURKB
Signal Transduction	1	AURKB
Signaling by Rho GTPases	1	AURKB
RHO GTPase Effectors	1	AURKB
Separation of Sister Chromatids	1	AURKB
Resolution of Sister Chromatid Cohesion	1	AURKB
Mitotic Metaphase and Anaphase	1	AURKB
Regulation of PLK1 Activity at G2/M Transition	1	AURKA
Mitotic G2-G2/M phases	1	AURKA
RHO GTPases Activate Formins	1	AURKB
TP53 Regulates Transcription of Cell Cycle Genes	1	AURKA
TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest	1	AURKA
Mitotic Prometaphase	1	AURKB

Dominant GO biological processes

GO term	Targets
mitotic cell cycle	2
protein phosphorylation	2
spindle organization	2
mitotic spindle organization	2
regulation of cytokinesis	2
cell division	2
regulation of signal transduction by p53 class mediator	2
regulation of microtubule-based process	2
cell cycle G2/M phase transition	2
positive regulation of cell cycle process	2
G2/M transition of mitotic cell cycle	1
apoptotic process	1
spindle assembly involved in female meiosis I	1
mitotic centrosome separation	1
response to wounding	1

Indications & clinical

Indications

4 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
acute myeloid leukemia	2	MONDO:0018874	EFO:0000222
lymphoma	1	MONDO:0005062	EFO:0000574
neoplasm	1	MONDO:0005070	EFO:0000616
myeloid leukemia	1	MONDO:0004643	MONDO:0004643

Clinical trials

Total trials: 8.

Phase distribution

Phase	Trials
PHASE1	6
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00952588	PHASE2/PHASE3	COMPLETED	Study to Investigate the Efficacy, Safety and Tolerability of AZD1152 Alone and in Combination With Low Dose Cytosine Arabinoside (LDAC)in Acute Myeloid Leukaemia (AML) Patients
NCT01354392	PHASE1/PHASE2	COMPLETED	AZD1152 in Diffuse Large B-cell Lymphoma
NCT00497679	PHASE1	TERMINATED	AZD1152 in Patients With Advanced Solid Malignancies-Study 3
NCT00497731	PHASE1	TERMINATED	AZD1152 in Patients With Advanced Solid Malignancies-Study 1
NCT00497991	PHASE1	COMPLETED	Safety, Tolerability, PK and Efficacy of AZD1152 in Patients With Relapsed Acute Myeloid Leukemia
NCT00530699	PHASE1	COMPLETED	Safety, Tolerability and PK of AZD1152 in Patients With Relapsed Acute Myeloid Leukaemia (AML)
NCT00926731	PHASE1	COMPLETED	Study to Assess the Safety and Tolerability of AZD1152 in Combination With Low Dose Cytosine Arabinoside (LDAC)
NCT01019161	PHASE1	COMPLETED	An Open Label, Single Centre Mass Balance C14 Study in Patients With Acute Myeloid Leukaemia (AML)

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

82 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
belumosudil	ChEMBL + PubChem	Phase 4 (approved)	AURKA, AURKB
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	AURKA, AURKB
FOSTAMATINIB	ChEMBL + PubChem	Phase 4 (approved)	AURKA, AURKB
PAZOPANIB	ChEMBL + PubChem	Phase 4 (approved)	AURKA, AURKB
AXITINIB	ChEMBL	Phase 4 (approved)	AURKA, AURKB
CABOZANTINIB	ChEMBL	Phase 4 (approved)	AURKA, AURKB
DASATINIB	ChEMBL	Phase 4 (approved)	AURKA, AURKB
ENTRECTINIB	ChEMBL	Phase 4 (approved)	AURKA, AURKB
ERLOTINIB	ChEMBL	Phase 4 (approved)	AURKA, AURKB
FEDRATINIB	ChEMBL	Phase 4 (approved)	AURKA, AURKB
INAMRINONE	ChEMBL	Phase 4 (approved)	AURKA, AURKB
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	AURKA, AURKB
SORAFENIB	ChEMBL	Phase 4 (approved)	AURKA, AURKB
SUNITINIB	ChEMBL	Phase 4 (approved)	AURKA, AURKB
UPADACITINIB	ChEMBL	Phase 4 (approved)	AURKA, AURKB
ALISERTIB	ChEMBL	Phase 3	AURKA, AURKB
DEFACTINIB	ChEMBL	Phase 3	AURKA, AURKB
LESTAURTINIB	ChEMBL	Phase 3	AURKA, AURKB
LINIFANIB	ChEMBL	Phase 3	AURKA, AURKB
ORANTINIB	ChEMBL	Phase 3	AURKA, AURKB
AT-9283	ChEMBL	Phase 2	AURKA, AURKB
AZD-1480	ChEMBL	Phase 2	AURKA, AURKB
BEMCENTINIB	ChEMBL	Phase 2	AURKA, AURKB
BMS-754807	ChEMBL	Phase 2	AURKA, AURKB
DANUSERTIB	ChEMBL	Phase 2	AURKA, AURKB
DEFOSBARASERTIB	ChEMBL	Phase 2	AURKA, AURKB
DUBERMATINIB	ChEMBL	Phase 2	AURKA, AURKB
ELLAGIC ACID	ChEMBL	Phase 2	AURKA, AURKB
ENMD-2076	ChEMBL	Phase 2	AURKA, AURKB
FORETINIB	ChEMBL	Phase 2	AURKA, AURKB
ILORASERTIB	ChEMBL	Phase 2	AURKA, AURKB
KW-2450	ChEMBL	Phase 2	AURKA, AURKB
MILCICLIB	ChEMBL	Phase 2	AURKA, AURKB
MOBINITINIB	ChEMBL	Phase 2	AURKA, AURKB
OCIFISERTIB	ChEMBL	Phase 2	AURKA, AURKB
OSI-632	ChEMBL	Phase 2	AURKA, AURKB
R-406	ChEMBL	Phase 2	AURKA, AURKB
TOZASERTIB	ChEMBL	Phase 2	AURKA, AURKB
Afatinib	PubChem	Approved	AURKA, AURKB
Binimetinib	PubChem	Approved	AURKA, AURKB
dacomitinib	PubChem	Approved	AURKA, AURKB
Idelalisib	PubChem	Approved	AURKA, AURKB
regorafenib	PubChem	Approved	AURKA, AURKB
Selumetinib	PubChem	Approved	AURKA, AURKB
Trametinib	PubChem	Approved	AURKA, AURKB
BRIGATINIB	ChEMBL	Phase 4 (approved)	AURKA
DOXORUBICIN	ChEMBL	Phase 4 (approved)	AURKA
GILTERITINIB	ChEMBL	Phase 4 (approved)	AURKA
LAPATINIB	ChEMBL	Phase 4 (approved)	AURKB
LENVATINIB	ChEMBL	Phase 4 (approved)	AURKB
NICLOSAMIDE	ChEMBL	Phase 4 (approved)	AURKA
NINTEDANIB	ChEMBL	Phase 4 (approved)	AURKB
PACRITINIB	ChEMBL	Phase 4 (approved)	AURKB
PEXIDARTINIB	ChEMBL	Phase 4 (approved)	AURKB
QUIZARTINIB	ChEMBL	Phase 4 (approved)	AURKB
SORAFENIB TOSYLATE	ChEMBL	Phase 4 (approved)	AURKB
SULFADIAZINE	ChEMBL	Phase 4 (approved)	AURKA
TIVOZANIB	ChEMBL	Phase 4 (approved)	AURKB
TOFACITINIB	ChEMBL	Phase 4 (approved)	AURKB
VANDETANIB	ChEMBL	Phase 4 (approved)	AURKB