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Buparlisib

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Also known as Bkm-120BKM-120NXNVP-BKM-120NVP-BKM120SID137275918BKM120 (NVP-BKM120)BKM120

Summary

Buparlisib (CHEMBL2017974) is a phase-3 clinical-stage small-molecule EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor targeting PIK3CA; indicated across 28 conditions including breast neoplasm and head and neck cancer; with CIViC clinical evidence for 5 variant-indication associations (e.g. PIK3CA Mutation in glioblastoma).

At a glance

  • Status: Max clinical phase 3 (not approved)
  • Modality: Small molecule
  • Targets: 1 (PIK3CA)
  • Indications: 28 conditions
  • Clinical trials: 78
  • Precision-oncology evidence (CIViC): 5 variant–indication associations
  • Chemistry: 410.4 Da · C18H21F3N6O2

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL2017974
NameBuparlisib
TypeSmall molecule
Max phase3
FDA approvedno
PubChem CID16654980
ChEBICHEBI:71954
Molecular formulaC18H21F3N6O2
Molecular weight410.4
InChIKeyCWHUFRVAEUJCEF-UHFFFAOYSA-N

SMILES: C1COCCN1C2=NC(=NC(=C2)C3=CN=C(C=C3C(F)(F)F)N)N4CCOCC4

IUPAC name: 5-(2,6-dimorpholin-4-ylpyrimidin-4-yl)-4-(trifluoromethyl)pyridin-2-amine

ChEBI definition: An aminopyridine that is 4-(trifluoromethyl)pyridin-2-amine substituted at position 5 by a 2,6-di(morpholin-4-yl)pyrimidin-4-y group. A selective PI3K inhibitor with anti-tumour properties.

Pharmacological roles (ChEBI): EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor, antineoplastic agent.

Also known as: Bkm-120, BKM-120, BKM-120NX, Buparlisib, NVP-BKM-120, NVP-BKM120, SID137275918, BUPARLISIB, BKM120 (NVP-BKM120), BKM120

Parent form; salt/anhydrous children: CHEMBL2364604

Patent coverage: 2,431 distinct patent families (6,568 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 4,954 (75%) 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
PIK3CAphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alphaInhibition7.5242.7%P42336

Broader ChEMBL bioactivity targets: 18 (assay-derived). Sample: Phosphatidylinositol 3-kinase catalytic subunit type 3, Serine/threonine-protein kinase mTOR, PI3-kinase p110-alpha/p85-alpha, PI3-kinase p110-delta/p85-alpha, Phosphatidylinositol 3-kinase regulatory subunit alpha, Serine/threonine-protein kinase mTOR, PI3K p110 beta/p85 alpha, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform, DNA-dependent protein kinase catalytic subunit, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform.

Bioactivity

ChEMBL activities: 82 potent at pChembl ≥ 5 of 84 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
PIK3CA8.46Kd3.5nMCHEMBL_ACT_18088187
PIK3R17.96IC5011nMCHEMBL_ACT_18553330
PIK3CA7.89IC5013nMCHEMBL_ACT_24669609
MTOR7.72Kd19nMCHEMBL_ACT_18088211
PIK3CA7.7Ki20nMCHEMBL_ACT_18813192
PIK3CA7.7IC5020nMCHEMBL_ACT_18882205
PIK3CA7.6IC5025nMCHEMBL_ACT_18553332
PIK3R17.54IC5029nMCHEMBL_ACT_18553328
PIK3CA7.52IC5030nMCHEMBL_ACT_10852314
PIK3CA7.52IC5030nMCHEMBL_ACT_14553187
PIK3CA7.52IC5030nMCHEMBL_ACT_15181339
PIK3CA7.52IC5030nMCHEMBL_ACT_15223692
PIK3CB7.44Kd36nMCHEMBL_ACT_18088193
PIK3R17.4IC5040nMCHEMBL_ACT_18553201
PIK3CA7.36IC5044nMCHEMBL_ACT_24817502
PIK3CA7.35IC5045nMCHEMBL_ACT_18088161
PIK3CA7.3IC5050nMCHEMBL_ACT_24984315
PIK3CA7.28IC5052nMCHEMBL_ACT_10852409
PIK3CA7.28IC5052nMCHEMBL_ACT_19139821
PIK3CA7.28IC5052.48nMCHEMBL_ACT_19151910
PIK3CA7.28IC5052nMCHEMBL_ACT_24978674
PIK3CA7.28IC5052nMCHEMBL_ACT_25556606
PIK3CA7.28IC5052nMCHEMBL_ACT_25892696
PIK3CA7.28IC5052nMCHEMBL_ACT_26224987
PIK3CA7.24IC5058nMCHEMBL_ACT_10852410
PIK3CA7.06IC5087nMCHEMBL_ACT_18088068
MTOR7.03IC5094nMCHEMBL_ACT_18088153
PIK3CA7IC5099nMCHEMBL_ACT_10852411
PIK3CA6.96IC50111nMCHEMBL_ACT_18088072
PIK3CD6.96IC50110nMCHEMBL_ACT_18088155

Target pathways

Aggregated over 1 target gene(s): PIK3CA.

Top Reactome pathways

60 total, by targets touching each:

PathwayTargetsGenes
PI3K Cascade1PIK3CA
IRS-mediated signalling1PIK3CA
GPVI-mediated activation cascade1PIK3CA
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants1PIK3CA
PI3K events in ERBB4 signaling1PIK3CA
PIP3 activates AKT signaling1PIK3CA
Signaling by SCF-KIT1PIK3CA
Synthesis of PIPs at the plasma membrane1PIK3CA
GAB1 signalosome1PIK3CA
Signaling by cytosolic FGFR1 fusion mutants1PIK3CA
Downstream signal transduction1PIK3CA
PI3K events in ERBB2 signaling1PIK3CA
PI3K/AKT activation1PIK3CA
Signaling by ALK1PIK3CA
Downstream TCR signaling1PIK3CA
Role of phospholipids in phagocytosis1PIK3CA
Tie2 Signaling1PIK3CA
Constitutive Signaling by Aberrant PI3K in Cancer1PIK3CA
DAP12 signaling1PIK3CA
Role of LAT2/NTAL/LAB on calcium mobilization1PIK3CA
Nephrin family interactions1PIK3CA
CD28 dependent PI3K/Akt signaling1PIK3CA
G alpha (q) signalling events1PIK3CA
VEGFA-VEGFR2 Pathway1PIK3CA
Interleukin-3, Interleukin-5 and GM-CSF signaling1PIK3CA
Constitutive Signaling by EGFRvIII1PIK3CA
PI-3K cascade:FGFR11PIK3CA
PI-3K cascade:FGFR21PIK3CA
PI-3K cascade:FGFR31PIK3CA
PI-3K cascade:FGFR41PIK3CA

Dominant GO biological processes

GO termTargets
angiogenesis1
liver development1
vasculature development1
glucose metabolic process1
phagocytosis1
epidermal growth factor receptor signaling pathway1
insulin receptor signaling pathway1
positive regulation of lamellipodium assembly1
negative regulation of gene expression1
response to activity1
response to muscle inactivity1
negative regulation of macroautophagy1
cell migration1
actin cytoskeleton organization1
platelet activation1

Indications & clinical

Indications

28 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
breast neoplasm3MONDO:0021100EFO:0003869
head and neck cancer3MONDO:0005627EFO:0006859
thymoma2MONDO:0006456EFO:1000581
mantle cell lymphoma2MONDO:0018876EFO:1001469
neoplasm2MONDO:0005070EFO:0000616
B-cell chronic lymphocytic leukemia2MONDO:0004948EFO:0000095
glioblastoma2MONDO:0018177EFO:0000519
melanoma2MONDO:0005105EFO:0000756
non-small cell lung carcinoma2MONDO:0005233EFO:0003060
head and neck squamous cell carcinoma2MONDO:0010150EFO:0000181
endometrium neoplasm2MONDO:0021251MONDO:0011962
liver disorder1MONDO:0005154EFO:0001421
leukemia1MONDO:0005059EFO:0000565
diffuse large B-cell lymphoma1MONDO:0018905EFO:0000403
small cell lung carcinoma1MONDO:0008433EFO:0000702
kidney disorder1MONDO:0005240EFO:0003086
lung neoplasm1MONDO:0021117MONDO:0008903
follicular lymphoma1MONDO:0018906MONDO:0018906
primary myelofibrosis1MONDO:0009692MONDO:0044903
gastrointestinal stromal tumor1MONDO:0011719MONDO:0011719
lymphoma1MONDO:0005062EFO:0000574
lymphoid leukemia1MONDO:0005402EFO:0004289
colorectal neoplasm1MONDO:0005335MONDO:0005575

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

Clinical trials

Total trials: 78.

Phase distribution

PhaseTrials
PHASE136
PHASE231
PHASE1/PHASE25
PHASE33
EARLY_PHASE12
PHASE2/PHASE31

Top trials by phase / activity

NCTPhaseStatusTitle
NCT01572727PHASE2/PHASE3COMPLETEDA Study of the Experimental Drug BKM120 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Activation
NCT01610284PHASE3COMPLETEDPhase III Study of BKM120/Placebo With Fulvestrant in Postmenopausal Patients With Hormone Receptor Positive HER2-negative Locally Advanced or Metastatic Breast Cancer Refractory to Aromatase Inhibitor
NCT01633060PHASE3TERMINATEDA Phase III Study of BKM120 With Fulvestrant in Patients With HR+,HER2-, AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTORi
NCT04338399PHASE3COMPLETEDThe BURAN Study of Buparlisib in Patients With Recurrent or Metastatic HNSCC
NCT01132664PHASE1/PHASE2TERMINATEDPhase 1b/2 Study of BKM120 Plus Trastuzumab in Patients With HER2-positive Breast Cancer
NCT01289041PHASE2COMPLETEDBKM120 as Second-line Therapy for Advanced Endometrial Cancer
NCT01297491PHASE2COMPLETEDSafety and Efficacy of BKM120 in Patients With Metastatic Non-small Cell Lung Cancer
NCT01339052PHASE2COMPLETEDPhase II Study of BKM120 for Subjects With Recurrent Glioblastoma
NCT01349660PHASE1/PHASE2COMPLETEDCombination of BKM120 and Bevacizumab in Refractory Solid Tumors and Relapsed/Refractory Glioblastoma Multiforme
NCT01385293PHASE2TERMINATEDBKM120 in Metastatic Castration-resistant Prostate Cancer
NCT01397877PHASE2COMPLETEDGINECO-EN102b - BKM120 as Monotherapy in the Treatment of Initial or Recurrent Metastatic Endometrial Cancer
NCT01487265PHASE2COMPLETEDTrial of Erlotinib and BKM120 in Patients With Advanced Non Small Cell Lung Cancer Previously Sensitive to Erlotinib
NCT01501604PHASE2WITHDRAWNBKM120 in Cancers With PIK3CA Activating Mutations
NCT01527877PHASE2UNKNOWNStudy of BKM120 in Advanced Squamous Cell Carcinoma of Head and Neck
NCT01550380PHASE2WITHDRAWNBKM120 in Advanced, Metastatic, or Recurrent Endometrial Cancers
NCT01551030PHASE2COMPLETEDBuparlisib in Metastatic Transitional Cell Carcinoma of the Urothelium
NCT01589861PHASE1/PHASE2TERMINATEDSafety and Efficacy of BKM120 and Lapatinib in HER2+/PI3K-activated, Trastuzumab-resistant Advanced Breast Cancer
NCT01591421PHASE1/PHASE2COMPLETEDP13Kinase Inhibitor BKM120 in Combination With Panitumumab in Metastatic/Advanced RAS-Wild Type Colorectal Cancer.
NCT01613677PHASE2WITHDRAWNPhase II, Open Label, Non-randomized, Trial of BKM120 for Metastatic or Locally Advanced Cervical Cancer
NCT01629615PHASE2COMPLETEDA Trial of BKM120 (a PI3K Inhibitor) in Patients With Triple Negative Metastatic Breast Cancer
NCT01693614PHASE2COMPLETEDSafety and Efficacy of BKM120 in Relapsed and Refractory NHL
NCT01695473PHASE2TERMINATEDNeoadjuvant BKM120 in High-risk Prostate Cancer
NCT01737450PHASE2COMPLETEDActivity and Safety Study of BKM120 in Monotherapy in Patient With Metastatic Head and Neck Cancer Recurrent or Progressive
NCT01790932PHASE2COMPLETEDBKM120 For Triple Negative Breast Cancer
NCT01806649PHASE2TERMINATEDBKM120 in Esophageal Squamous Cell Carcinoma After Failure of First Line Chemotherapy
NCT01816594PHASE2COMPLETEDNeoPHOEBE: Neoadjuvant Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive Primary Breast Cancer
NCT01830504PHASE2UNKNOWNA Multicenter Phase II Pilot Open Label
NCT01833169PHASE2COMPLETEDBKM120 for Patients With PI3K-activated Tumors
NCT01852292PHASE2TERMINATEDStudy of Efficacy and Safety of Buparlisib (BKM120) Plus Paclitaxel Versus Placebo Plus Paclitaxel in Recurrent or Metastatic Head and Neck Cancer Previously Pre-treated With a Platinum Therapy
NCT01870726PHASE1/PHASE2TERMINATEDSafety and Efficacy of INC280 and Buparlisib (BKM120) in Patients With Recurrent Glioblastoma
NCT01923168PHASE2COMPLETEDStudy of Letrozole With or Without BYL719 or Buparlisib, for the Neoadjuvant Treatment of Postmenopausal Women
NCT01953445PHASE2WITHDRAWNPaclitaxel and BKM120 Before Surgery in Treating Patients With Stage II or III Estrogen Receptor-Positive and HER2-Negative Breast Cancer
NCT02000882PHASE2COMPLETEDSTAR Cape+BKM120 MBC With Brain Met
NCT02159066PHASE2COMPLETEDLGX818 and MEK162 in Combination With a Third Agent (BKM120, LEE011, BGJ398 or INC280) in Advanced BRAF Melanoma
NCT02220855PHASE2COMPLETEDA Study of BKM120 (Buparlisib) in Relapsed or Refractory Thymomas
NCT02301364PHASE2COMPLETEDBuparlisib (BKM120) In Patients With Recurrent/Refractory Primary Central Nervous System Lymphoma (PCNSL) and Recurrent/Refractory Secondary Central Nervous System Lymphoma (SCNSL)
NCT02303041PHASE2TERMINATEDPilot Study of Sonidegib and Buparlisib in Treating Patients With Advanced or Metastatic Basal Cell Carcinoma
NCT02340780PHASE2COMPLETEDBuparlisib in Patients With Relapsed and Refractory Chronic Lymphocytic Leukemia
NCT02404844PHASE2COMPLETEDTrial of BKM120/Tamoxifen-combination in Patients With HR-pos, HER2-neg Breast Cancer
NCT02452294PHASE2UNKNOWNBuparlisib in Melanoma Patients Suffering From Brain Metastases (BUMPER)

Clinical evidence (CIViC)

Variant × indication × effect (5 predictive associations from 5 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
PIK3CA MutationGlioblastomaSensitivity/ResponseBuparlisibCIViC BEID7072
PIK3R1 MutationGlioblastomaSensitivity/ResponseBuparlisibCIViC BEID7073
PTEN LossSolid TumorSensitivity/ResponseBuparlisib + Carboplatin + PaclitaxelCIViC BEID5957
PTEN MutationGlioblastomaSensitivity/ResponseBuparlisibCIViC BEID7074
PTEN LossCancerSensitivity/ResponseCarboplatin + Buparlisib + PaclitaxelCIViC CEID714

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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)PIK3CA
IDELALISIBChEMBL + PubChemPhase 4 (approved)PIK3CA
ALPELISIBChEMBLPhase 4 (approved)PIK3CA
BELINOSTATChEMBLPhase 4 (approved)PIK3CA
COPANLISIBChEMBLPhase 4 (approved)PIK3CA
DASATINIBChEMBLPhase 4 (approved)PIK3CA
DUVELISIBChEMBLPhase 4 (approved)PIK3CA
FEDRATINIBChEMBLPhase 4 (approved)PIK3CA
INAVOLISIBChEMBLPhase 4 (approved)PIK3CA
LENIOLISIBChEMBLPhase 4 (approved)PIK3CA
MIDOSTAURINChEMBLPhase 4 (approved)PIK3CA
ROMIDEPSINChEMBLPhase 4 (approved)PIK3CA
SUNITINIBChEMBLPhase 4 (approved)PIK3CA
DACTOLISIBChEMBLPhase 3PIK3CA
EPIGALOCATECHIN GALLATEChEMBLPhase 3PIK3CA
GEDATOLISIBChEMBLPhase 3PIK3CA
IPATASERTIBChEMBLPhase 3PIK3CA
LESTAURTINIBChEMBLPhase 3PIK3CA
RESVERATROLChEMBLPhase 3PIK3CA
TASELISIBChEMBLPhase 3PIK3CA
AMG-319ChEMBLPhase 2PIK3CA
APITOLISIBChEMBLPhase 2PIK3CA
AZD-6482ChEMBLPhase 2PIK3CA
AZD-8154ChEMBLPhase 2PIK3CA
BERZOSERTIBChEMBLPhase 2PIK3CA
BGT-226 FREE BASEChEMBLPhase 2PIK3CA
BI-2536ChEMBLPhase 2PIK3CA
BIMIRALISIBChEMBLPhase 2PIK3CA
CC-115ChEMBLPhase 2PIK3CA
EGANELISIBChEMBLPhase 2PIK3CA
FIMEPINOSTATChEMBLPhase 2PIK3CA
IZORLISIBChEMBLPhase 2PIK3CA
MMV-048ChEMBLPhase 2PIK3CA
NEMIRALISIBChEMBLPhase 2PIK3CA
OMIPALISIBChEMBLPhase 2PIK3CA
ONATASERTIBChEMBLPhase 2PIK3CA
OSI-027ChEMBLPhase 2PIK3CA
PAXALISIBChEMBLPhase 2PIK3CA
PF-04691502ChEMBLPhase 2PIK3CA
PICTILISIBChEMBLPhase 2PIK3CA
PILARALISIBChEMBLPhase 2PIK3CA
QUISINOSTATChEMBLPhase 2PIK3CA
RAFOXANIDEChEMBLPhase 2PIK3CA
RISOVALISIBChEMBLPhase 2PIK3CA
ROGINOLISIBChEMBLPhase 2PIK3CA
SAMOTOLISIBChEMBLPhase 2PIK3CA
SAPANISERTIBChEMBLPhase 2PIK3CA
SERABELISIBChEMBLPhase 2PIK3CA
SONOLISIBChEMBLPhase 2PIK3CA
TG100-115ChEMBLPhase 2PIK3CA
VISTUSERTIBChEMBLPhase 2PIK3CA
VOXTALISIBChEMBLPhase 2PIK3CA
ZSTK-474ChEMBLPhase 2PIK3CA
AfatinibPubChemApprovedPIK3CA
PazopanibPubChemApprovedPIK3CA
SelumetinibPubChemApprovedPIK3CA

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
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Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot