◎ Sugi Atlas

Atlas / Drug / Alisertib

Alisertib

drug
On this page

Also known as MLN 8237Mln-8237MLN8237CHEMBL483158ALISERTIB SODIUMALISERTIB (MLN8237)SID103905632SID137276087SID174006392MLN8237 (ALISERTIB)Allsertib

Summary

Alisertib (CHEMBL483158) is a phase-3 clinical-stage small-molecule Aurora kinase inhibitor targeting AURKA; indicated across 25 conditions including peripheral t-cell lymphoma, not otherwise specified and prostate adenocarcinoma; with CIViC clinical evidence for 4 variant-indication associations (e.g. AURKA Overexpression in esophagus adenocarcinoma).

At a glance

  • Status: Max clinical phase 3 (not approved)
  • Modality: Small molecule
  • Targets: 1 (AURKA)
  • Indications: 25 conditions
  • Clinical trials: 62
  • Precision-oncology evidence (CIViC): 4 variant–indication associations
  • Chemistry: 518.9 Da · C27H20ClFN4O4

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL483158
NameAlisertib
TypeSmall molecule
Max phase3
FDA approvedno
PubChem CID24771867
ChEBICHEBI:125628
Molecular formulaC27H20ClFN4O4
Molecular weight518.9
InChIKeyZLHFILGSQDJULK-UHFFFAOYSA-N

SMILES: COC1=C(C(=CC=C1)F)C2=NCC3=CN=C(N=C3C4=C2C=C(C=C4)Cl)NC5=CC(=C(C=C5)C(=O)O)OC

IUPAC name: 4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid

ChEBI definition: An organic heterotricyclic compound that is 5H-pyrimido[5,4-d][2]benzazepine substituted by (4-carboxy-3-methoxyphenyl)amino, 2-fluoro-6-methoxyphenyl, and chloro groups at positions 2, 7 and 9, respectively. It is an aurora A kinase inhibitor (IC50 = ~1 nM).

Pharmacological roles (ChEBI): Aurora kinase inhibitor, antineoplastic agent, apoptosis inducer, autophagy inducer.

Also known as: Alisertib, MLN 8237, Mln-8237, MLN-8237, MLN8237, ALISERTIB, CHEMBL483158, ALISERTIB SODIUM, ALISERTIB (MLN8237), SID103905632, SID137276087, SID174006392

Parent form; salt/anhydrous children: CHEMBL2103871, CHEMBL3586471

Patent coverage: 886 distinct patent families (2,305 SureChEMBL compound mentions), from 5 matched compound structure(s). One matched structure accounts for 2,090 (91%) 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).

GeneTargetActionpAffinityCancer dependencyUniProt
AURKAaurora kinase AInhibition999.4% (common-essential)O14965

Broader ChEMBL bioactivity targets: 54 (assay-derived). Sample: Leucine-rich repeat serine/threonine-protein kinase 2, Receptor tyrosine-protein kinase erbB-2, Tyrosine-protein kinase ABL1, Vascular endothelial growth factor receptor 1, Gamma-aminobutyric acid receptor subunit alpha-1, Epidermal growth factor receptor, Proto-oncogene tyrosine-protein kinase receptor Ret, Ephrin type-A receptor 2, Aurora kinase B, DnaJ homolog subfamily A member 1.

Bioactivity

ChEMBL activities: 99 potent at pChembl ≥ 5 of 100 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
AURKA10.4IC500.04nMCHEMBL_ACT_16763104
P974779.52Ki0.3nMCHEMBL_ACT_15622914
AURKA9.3Ki0.5nMCHEMBL_ACT_9586215
AURKA9.22IC500.6nMCHEMBL_ACT_17769939
AURKA9.22IC500.6nMCHEMBL_ACT_26947393
AURKA9IC501nMCHEMBL_ACT_13343478
AURKA9IC501nMCHEMBL_ACT_15152439
P974779IC501nMCHEMBL_ACT_15622939
AURKA9IC501nMCHEMBL_ACT_2526269
AURKB8.96IC501.1nMCHEMBL_ACT_16763125
AURKA8.92IC501.2nMCHEMBL_ACT_12112560
AURKA8.92IC501.2nMCHEMBL_ACT_18761182
AURKA8.92IC501.2nMCHEMBL_ACT_18878211
AURKA8.92IC501.2nMCHEMBL_ACT_20680951
AURKA8.92IC501.2nMCHEMBL_ACT_22395787
AURKA8.92IC501.2nMCHEMBL_ACT_24893122
AURKA8.92IC501.2nMCHEMBL_ACT_25755757
AURKB8.5Ki3.16nMCHEMBL_ACT_9577869
AURKA8.3Kd5nMCHEMBL_ACT_17884058
AURKA8.17IC506.7nMCHEMBL_ACT_16763154
AURKA8.17IC506.7nMCHEMBL_ACT_25755648
AURKA8.15IC507nMCHEMBL_ACT_15622934
AURKA7.88IC5013.3nMCHEMBL_ACT_24359161
AURKA7.84IC5014.5nMCHEMBL_ACT_26329845
AURKA7.82IC5015nMCHEMBL_ACT_25754192
AURKA7.8IC5016nMCHEMBL_ACT_25754191
AURKA7.8IC5016nMCHEMBL_ACT_25754193
AURKA7.5IC5032nMCHEMBL_ACT_25754194
EPHA27.5Ki31.62nMCHEMBL_ACT_9615255
PLK47.4Ki39.81nMCHEMBL_ACT_9528833

Target pathways

Aggregated over 1 target gene(s): AURKA.

Top Reactome pathways

24 total, by targets touching each:

PathwayTargetsGenes
Cell Cycle1AURKA
APC/C-mediated degradation of cell cycle proteins1AURKA
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G11AURKA
Generic Transcription Pathway1AURKA
Regulation of PLK1 Activity at G2/M Transition1AURKA
SUMOylation1AURKA
SUMO E3 ligases SUMOylate target proteins1AURKA
Transcriptional Regulation by TP531AURKA
Metabolism of proteins1AURKA
Mitotic G2-G2/M phases1AURKA
Regulation of mitotic cell cycle1AURKA
SUMOylation of DNA replication proteins1AURKA
Regulation of TP53 Activity1AURKA
Post-translational protein modification1AURKA
TP53 Regulates Transcription of Cell Cycle Genes1AURKA
TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest1AURKA
Regulation of TP53 Activity through Phosphorylation1AURKA
G2/M Transition1AURKA
Cell Cycle, Mitotic1AURKA
RNA Polymerase II Transcription1AURKA
Gene expression (Transcription)1AURKA
FBXL7 down-regulates AURKA during mitotic entry and in early mitosis1AURKA
AURKA Activation by TPX21AURKA
Interaction between PHLDA1 and AURKA1AURKA

Dominant GO biological processes

GO termTargets
G2/M transition of mitotic cell cycle1
mitotic cell cycle1
protein phosphorylation1
apoptotic process1
spindle organization1
mitotic spindle organization1
spindle assembly involved in female meiosis I1
mitotic centrosome separation1
response to wounding1
anterior/posterior axis specification1
regulation of G2/M transition of mitotic cell cycle1
negative regulation of gene expression1
peptidyl-serine phosphorylation1
regulation of protein stability1
negative regulation of protein binding1

Indications & clinical

Indications

25 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).

IndicationTrial phaseMONDOEFO
peripheral T-cell lymphoma, not otherwise specified3MONDO:0004964EFO:0000211
prostate adenocarcinoma2MONDO:0005082EFO:0000673
ovarian carcinoma2MONDO:0005140EFO:0001075
breast carcinoma2MONDO:0004989EFO:0000305
myelodysplastic syndrome2MONDO:0018881EFO:0000198
acute myeloid leukemia2MONDO:0018874EFO:0000222
small cell lung carcinoma2MONDO:0008433EFO:0000702
peritoneal neoplasm2MONDO:0006901MONDO:0002087
fallopian tube neoplasm2MONDO:0021092MONDO:0002158
breast neoplasm2MONDO:0021100MONDO:0007254
lymphoma1MONDO:0005062EFO:0000574
neoplasm1MONDO:0005070EFO:0000616
neuroblastoma1MONDO:0005072EFO:0000621
Burkitt lymphoma1MONDO:0007243EFO:0000309
diffuse large B-cell lymphoma1MONDO:0018905EFO:0000403
plasma cell myeloma1MONDO:0009693EFO:0001378
head and neck cancer1MONDO:0005627EFO:0006859
mantle cell lymphoma1MONDO:0018876EFO:1001469
follicular lymphoma1MONDO:0018906MONDO:0018906
head and neck squamous cell carcinoma1MONDO:0010150EFO:0000181
non-small cell lung carcinoma1MONDO:0005233EFO:0003060

4 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 62.

Phase distribution

PhaseTrials
PHASE133
PHASE220
PHASE1/PHASE26
Not specified2
PHASE31

Top trials by phase / activity

NCTPhaseStatusTitle
NCT01482962PHASE3COMPLETEDAlisertib (MLN8237) or Investigator’s Choice in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma
NCT02114229PHASE2ACTIVE_NOT_RECRUITINGPhase 2 Study of Alisertib Therapy for Rhabdoid Tumors
NCT06095505PHASE2RECRUITINGA Study of Alisertib in Patients With Extensive Stage Small Cell Lung Cancer
NCT06369285PHASE2RECRUITINGA Study of Alisertib in Combination With Endocrine Therapy in Patients With HR-positive, HER2-negative Recurrent or Metastatic Breast Cancer
NCT07465757PHASE2NOT_YET_RECRUITINGA Study of Alisertib and Paclitaxel in Patients With Small Cell Lung Cancer (SCLC)
NCT00807495PHASE2COMPLETEDStudy of Alisertib (MLN8237) in Adults With Aggressive Non-Hodgkin’s Lymphoma
NCT00830518PHASE2COMPLETEDA Phase 2 Trial of MLN8237 in Adult Participants With Acute Myelogenous Leukemia and High-Grade Myelodysplastic Syndrome
NCT00853307PHASE2COMPLETEDMLN8237 for Treatment of Participants With Ovarian, Fallopian Tube, or Peritoneal Carcinoma
NCT01045421PHASE1/PHASE2COMPLETEDAlisertib in Adults With Nonhematological Malignancies, Followed by Alisertib in Lung, Breast, Head and Neck or Gastroesophageal Malignancies
NCT01091428PHASE2COMPLETEDAlisertib (MLN8237) in Participants With Ovarian, Fallopian Tube or Peritoneal Cancer Preceded by Phase 1 Study of MLN8237 Plus Paclitaxel Treatment of Ovary or Breast Cancer
NCT01154816PHASE2COMPLETEDAlisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia
NCT01397825PHASE1/PHASE2COMPLETEDMLN8237 in Patients With Relapsed or Refractory Aggressive B-Cell Lymphoma Treated With Rituximab +/- Vincristine
NCT01466881PHASE2COMPLETEDAlisertib in Treating Patients With Relapsed or Refractory Peripheral T-Cell Non-Hodgkin Lymphoma
NCT01471964PHASE1/PHASE2TERMINATEDStudy to Assess Safety and Tolerability of MLN8237, In Combination With Erlotinib to Treat Non-Small Cell Lung Cancer
NCT01601535PHASE1/PHASE2COMPLETEDStudy of MLN8237 in Combination With Irinotecan and Temozolomide
NCT01637961PHASE2COMPLETEDAlisertib in Treating Patients With Recurrent or Persistent Leiomyosarcoma of the Uterus
NCT01653028PHASE2COMPLETEDAlisertib in Treating Patients With Advanced or Metastatic Sarcoma
NCT01799278PHASE2COMPLETEDA Phase II Trial of MLN8237 in Patients With Metastatic Castrate Resistant and Neuroendocrine Prostate Cancer
NCT01812005PHASE2TERMINATEDAlisertib With and Without Rituximab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
NCT01848067PHASE1/PHASE2COMPLETEDAlisertib, Abiraterone Acetate and Prednisone in Treating Patients With Hormone-Resistant Prostate Cancer
NCT02038647PHASE2COMPLETEDPhase 2 Study of Alisertib (MLN8237) in Combination With Paclitaxel Versus Placebo in Combination With Paclitaxel as Second Line Therapy for Small Cell Lung Cancer (SCLC)
NCT02109328PHASE2COMPLETEDAlisertib in Chemotherapy-pretreated Urothelial Cancer
NCT02187991PHASE2COMPLETEDStudy to Compare Alisertib With Paclitaxel vs. Paclitaxel Alone in Metastatic or Locally Recurrent Breast Cancer
NCT02293005PHASE2COMPLETEDPhase II Trial of Alisertib (MLN8237) in Salvage Malignant Mesothelioma
NCT02560025PHASE2COMPLETEDPhase II Trial of Alisertib With Induction Chemotherapy in High-risk AML
NCT02860000PHASE2COMPLETEDAlisertib With or Without Fulvestrant in Treating Patients With Locally Advanced or Metastatic, Endocrine-Resistant Breast Cancer
NCT04555837PHASE1/PHASE2COMPLETEDAlisertib and Pembrolizumab for the Treatment of Patients With Rb-deficient Head and Neck Squamous Cell Cancer
NCT01695941PHASE1ACTIVE_NOT_RECRUITINGAlisertib, Bortezomib, and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or B-cell Low Grade Non-Hodgkin Lymphoma
NCT04085315PHASE1RECRUITINGAlisertib in Combination With Osimertinib in Metastatic EGFR-mutant Lung Cancer
NCT00500903PHASE1COMPLETEDA Study of MLN8237, a Novel Aurora A Kinase Inhibitor, in Participants With Advanced Solid Tumors
NCT00651664PHASE1COMPLETEDA Phase I Clinical and Pharmacodynamic Study of MLN8237, A Novel Aurora A Kinase Inhibitor, in Participants With Advanced Malignancies
NCT00697346PHASE1COMPLETEDStudy of MLN8237 in Participants With Advanced Hematological Malignancies
NCT00962091PHASE1COMPLETEDStudy of MLN8237 in Participants With Advanced Solid Tumors
NCT01094288PHASE1COMPLETEDA Phase 1 Study of Alisertib Participants With Advanced Solid Tumors Including Castration-Resistant Prostate Cancer Receiving a Standard Docetaxel Regimen
NCT01512758PHASE1COMPLETEDA Study of Alisertib (MLN8237) in Adult East Asian Participants With Advanced Solid Tumors or Lymphomas
NCT01540682PHASE1COMPLETEDMLN8237 in Head and Neck Cancer
NCT01567709PHASE1COMPLETEDAlisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma
NCT01613261PHASE1WITHDRAWNStudy of TAK-733 in Combination With Alisertib in Adult Patients With Advanced Nonhematologic Malignancies
NCT01639911PHASE1COMPLETEDPhase I Study of MLN8237 and Pazopanib in Patients With Solid Tumors
NCT01677559PHASE1COMPLETEDCombining MLN8237 With Nab-Paclitaxel in Patients With Advanced Solid Malignancies

Clinical evidence (CIViC)

Variant × indication × effect (4 predictive associations from 4 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
AURKA OverexpressionEsophagus AdenocarcinomaSensitivity/ResponseAlisertib + CisplatinCIViC DEID9627
AURKB OverexpressionHead And Neck Squamous Cell CarcinomaSensitivity/ResponseAlisertib + Barasertib + CopanlisibCIViC DEID10836
KRAS OverexpressionGastrointestinal CarcinomaSensitivity/ResponseAlisertibCIViC DEID10154
AURKA AmplificationEsophagus AdenocarcinomaSensitivity/ResponseAlisertib + CisplatinCIViC EEID456

Pharmacology

Pharmacogenomics

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

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.

56 molecules share ≥1 primary target. Top 56 by shared-target count:

MoleculeSourceStatusShared targets
CRIZOTINIBChEMBL + PubChemPhase 4 (approved)AURKA
FOSTAMATINIBChEMBL + PubChemPhase 4 (approved)AURKA
PAZOPANIBChEMBL + PubChemPhase 4 (approved)AURKA
AXITINIBChEMBLPhase 4 (approved)AURKA
BRIGATINIBChEMBLPhase 4 (approved)AURKA
CABOZANTINIBChEMBLPhase 4 (approved)AURKA
DASATINIBChEMBLPhase 4 (approved)AURKA
DOXORUBICINChEMBLPhase 4 (approved)AURKA
ENTRECTINIBChEMBLPhase 4 (approved)AURKA
ERLOTINIBChEMBLPhase 4 (approved)AURKA
FEDRATINIBChEMBLPhase 4 (approved)AURKA
GILTERITINIBChEMBLPhase 4 (approved)AURKA
INAMRINONEChEMBLPhase 4 (approved)AURKA
MIDOSTAURINChEMBLPhase 4 (approved)AURKA
NICLOSAMIDEChEMBLPhase 4 (approved)AURKA
SORAFENIBChEMBLPhase 4 (approved)AURKA
SULFADIAZINEChEMBLPhase 4 (approved)AURKA
SUNITINIBChEMBLPhase 4 (approved)AURKA
UPADACITINIBChEMBLPhase 4 (approved)AURKA
BARASERTIBChEMBLPhase 3AURKA
DEFACTINIBChEMBLPhase 3AURKA
LESTAURTINIBChEMBLPhase 3AURKA
LINIFANIBChEMBLPhase 3AURKA
ORANTINIBChEMBLPhase 3AURKA
AT-9283ChEMBLPhase 2AURKA
AZD-1480ChEMBLPhase 2AURKA
BEMCENTINIBChEMBLPhase 2AURKA
BIIB-091ChEMBLPhase 2AURKA
BMS-754807ChEMBLPhase 2AURKA
CENISERTIBChEMBLPhase 2AURKA
CEP-11981ChEMBLPhase 2AURKA
DANUSERTIBChEMBLPhase 2AURKA
DEFOSBARASERTIBChEMBLPhase 2AURKA
DUBERMATINIBChEMBLPhase 2AURKA
ELLAGIC ACIDChEMBLPhase 2AURKA
ENMD-2076ChEMBLPhase 2AURKA
FEXAGRATINIBChEMBLPhase 2AURKA
FORETINIBChEMBLPhase 2AURKA
GANDOTINIBChEMBLPhase 2AURKA
ILORASERTIBChEMBLPhase 2AURKA
KW-2450ChEMBLPhase 2AURKA
MILCICLIBChEMBLPhase 2AURKA
MK-2461ChEMBLPhase 2AURKA
MOBINITINIBChEMBLPhase 2AURKA
OCIFISERTIBChEMBLPhase 2AURKA
OSI-632ChEMBLPhase 2AURKA
R-406ChEMBLPhase 2AURKA
TOZASERTIBChEMBLPhase 2AURKA
AfatinibPubChemApprovedAURKA
belumosudilPubChemApprovedAURKA
BinimetinibPubChemApprovedAURKA
dacomitinibPubChemApprovedAURKA
IdelalisibPubChemApprovedAURKA
regorafenibPubChemApprovedAURKA
SelumetinibPubChemApprovedAURKA
TrametinibPubChemApprovedAURKA

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot