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Gedatolisib

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Also known as PF-05212384PKI-587PF-05212384 (PKI-587)

Summary

Gedatolisib (CHEMBL592445) is a phase-3 clinical-stage small molecule targeting MTOR and PIK3CA; indicated across 7 conditions including breast neoplasm and endometrium neoplasm.

At a glance

  • Status: Max clinical phase 3 (not approved)
  • Modality: Small molecule
  • Targets: 2 (MTOR, PIK3CA)
  • Indications: 7 conditions
  • Clinical trials: 20
  • Chemistry: 615.7 Da · C32H41N9O4

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL592445
NameGedatolisib
TypeSmall molecule
Max phase3
FDA approvedno
PubChem CID44516953
Molecular formulaC32H41N9O4
Molecular weight615.7
InChIKeyDWZAEMINVBZMHQ-UHFFFAOYSA-N

SMILES: CN(C)C1CCN(CC1)C(=O)C2=CC=C(C=C2)NC(=O)NC3=CC=C(C=C3)C4=NC(=NC(=N4)N5CCOCC5)N6CCOCC6

IUPAC name: 1-[4-[4-(dimethylamino)piperidine-1-carbonyl]phenyl]-3-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl]urea

Also known as: Gedatolisib, PF-05212384, PKI-587, GEDATOLISIB, PF-05212384 (PKI-587)

Patent coverage: 1,112 distinct patent families (3,177 SureChEMBL compound mentions), from 1 matched compound structure(s). 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
MTORmechanistic target of rapamycin kinaseInhibition8.898.3% (common-essential)P42345
PIK3CAphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alphaInhibition9.442.7%P42336

Broader ChEMBL bioactivity targets: 7 (assay-derived). Sample: Phosphatidylinositol 3-kinase catalytic subunit type 3, Serine/threonine-protein kinase mTOR, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta.

Bioactivity

ChEMBL activities: 42 potent at pChembl ≥ 5 of 42 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
PIK3CA9.4IC500.4nMCHEMBL_ACT_14553165
PIK3CA9.4IC500.4nMCHEMBL_ACT_18861747
PIK3CA9.4IC500.4nMCHEMBL_ACT_24773328
MTOR9.4IC500.4nMCHEMBL_ACT_25872952
PIK3CA9.4IC500.4nMCHEMBL_ACT_25892699
PIK3CA9.4IC500.4nMCHEMBL_ACT_3120627
PIK3CA9.4IC500.4nMCHEMBL_ACT_6292474
MTOR9.4IC500.4nMCHEMBL_ACT_6292512
PIK3C2B9.34Kd0.46nMCHEMBL_ACT_18088216
PIK3CA9.22IC500.6nMCHEMBL_ACT_3121472
PIK3CA9.22IC500.6nMCHEMBL_ACT_3121473
MTOR9.03Kd0.94nMCHEMBL_ACT_18088210
PIK3CA9Kd1nMCHEMBL_ACT_18088186
MTOR9IC501nMCHEMBL_ACT_18861743
MTOR8.8IC501.6nMCHEMBL_ACT_14553164
MTOR8.8IC501.6nMCHEMBL_ACT_24773357
MTOR8.8IC501.6nMCHEMBL_ACT_3120673
MTOR8.68IC502.1nMCHEMBL_ACT_24417659
MTOR8.68IC502.1nMCHEMBL_ACT_25987025
MTOR8.6IC502.5nMCHEMBL_ACT_22488635
PIK3CB8.46Kd3.5nMCHEMBL_ACT_18088192
PIK3CG8.27IC505.4nMCHEMBL_ACT_14553169
PIK3CG8.27IC505.4nMCHEMBL_ACT_3120650
PIK3CG8.22IC506nMCHEMBL_ACT_18861745
PIK3CB8.22IC506nMCHEMBL_ACT_18861746
PIK3CA8.22IC506.04nMCHEMBL_ACT_22488615
PIK3CA8.22IC506nMCHEMBL_ACT_24417632
PIK3CA8.22IC506nMCHEMBL_ACT_25987006
PIK3CA8.22IC506nMCHEMBL_ACT_29217254
PIK3CB8.22IC506nMCHEMBL_ACT_3121470
PIK3CD8.22IC506nMCHEMBL_ACT_3121471
PIK3CD8.1IC508nMCHEMBL_ACT_18861744
PIK3CG7.96IC5011nMCHEMBL_ACT_6292493
PIK3CG7.62Kd24nMCHEMBL_ACT_18088198
PIK3CB7.56IC5027.8nMCHEMBL_ACT_24417685
PIK3CB7.56IC5027.8nMCHEMBL_ACT_25987068
PIK3CG7.38IC5041.4nMCHEMBL_ACT_24417692
PIK3CG7.38IC5041.4nMCHEMBL_ACT_25987076
PIK3CD7.12Kd76nMCHEMBL_ACT_18088204
PIK3CD6.81IC50156nMCHEMBL_ACT_24417699
PIK3CD6.81IC50156nMCHEMBL_ACT_25987084
PIK3C35.29Kd5100nMCHEMBL_ACT_18088222

Target pathways

Aggregated over 2 target gene(s): MTOR, PIK3CA.

Top Reactome pathways

97 total, by targets touching each:

PathwayTargetsGenes
PIP3 activates AKT signaling2MTOR, PIK3CA
CD28 dependent PI3K/Akt signaling2MTOR, PIK3CA
VEGFA-VEGFR2 Pathway2MTOR, PIK3CA
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells2MTOR, PIK3CA
PI3K Cascade1PIK3CA
IRS-mediated signalling1PIK3CA
GPVI-mediated activation cascade1PIK3CA
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants1PIK3CA
PI3K events in ERBB4 signaling1PIK3CA
Adaptive Immune System1MTOR
Signaling by SCF-KIT1PIK3CA
Signal Transduction1MTOR
Macroautophagy1MTOR
Disease1MTOR
MTOR signalling1MTOR
Synthesis of PIPs at the plasma membrane1PIK3CA
mTORC1-mediated signalling1MTOR
Immune System1MTOR
GAB1 signalosome1PIK3CA
Signaling by cytosolic FGFR1 fusion mutants1PIK3CA
Downstream signal transduction1PIK3CA
Signaling by VEGF1MTOR
PI3K events in ERBB2 signaling1PIK3CA
PI3K/AKT activation1PIK3CA
Signaling by ALK1PIK3CA
Downstream TCR signaling1PIK3CA
Role of phospholipids in phagocytosis1PIK3CA
Tie2 Signaling1PIK3CA
Generic Transcription Pathway1MTOR
PI3K/AKT Signaling in Cancer1MTOR
Constitutive Signaling by Aberrant PI3K in Cancer1PIK3CA
Cellular responses to stress1MTOR
DAP12 signaling1PIK3CA
Role of LAT2/NTAL/LAB on calcium mobilization1PIK3CA
Cellular response to heat stress1MTOR
HSF1-dependent transactivation1MTOR
Transcriptional Regulation by TP531MTOR
Nephrin family interactions1PIK3CA
Energy dependent regulation of mTOR by LKB1-AMPK1MTOR
Regulation of T cell activation by CD28 family1MTOR
Co-stimulation by CD281MTOR
G alpha (q) signalling events1PIK3CA
Interleukin-3, Interleukin-5 and GM-CSF signaling1PIK3CA
VEGFR2 mediated vascular permeability1MTOR
TP53 Regulates Metabolic Genes1MTOR
Regulation of TP53 Activity1MTOR
Constitutive Signaling by EGFRvIII1PIK3CA
PI-3K cascade:FGFR11PIK3CA
PI-3K cascade:FGFR21PIK3CA
PI-3K cascade:FGFR31PIK3CA

Dominant GO biological processes

GO termTargets
positive regulation of lamellipodium assembly2
negative regulation of macroautophagy2
cellular response to insulin stimulus2
TORC2 signaling2
anoikis2
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction2
cardiac muscle contraction2
insulin receptor signaling pathway2
phosphatidylinositol 3-kinase/protein kinase B signal transduction2
regulation of cell growth1
T-helper 1 cell lineage commitment1
heart morphogenesis1
heart valve morphogenesis1
energy reserve metabolic process1
‘de novo’ pyrimidine nucleobase biosynthetic process1

Indications & clinical

Indications

6 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)PhaseMONDOEFO
breast neoplasm3MONDO:0021100MONDO:0007254
endometrium neoplasm2MONDO:0021251EFO:0004230
acute myeloid leukemia2MONDO:0018874EFO:0000222
myelodysplastic syndrome2MONDO:0018881EFO:0000198
neoplasm1MONDO:0005070EFO:0000616
non-small cell lung carcinoma1MONDO:0005233EFO:0003060

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

Clinical trials

Total trials: 20.

Phase distribution

PhaseTrials
PHASE18
PHASE25
PHASE1/PHASE25
PHASE31
Not specified1

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05501886PHASE3ACTIVE_NOT_RECRUITINGGedatolisib Plus Fulvestrant With or Without Palbociclib vs Standard-of-Care for the Treatment of Patients With Advanced or Metastatic HR+/HER2- Breast Cancer (VIKTORIA-1)
NCT03675893PHASE2RECRUITINGRESOLVE: Abemaciclib + Letrozole +/- Metformin, Zotatifin, or Gedatolisib in Endometrial or Low-Grade Serous Ovarian Cancer
NCT03911973PHASE1/PHASE2ACTIVE_NOT_RECRUITINGGedatolisib Plus Talazoparib in Advanced Triple Negative or BRCA1/2 Positive, HER2 Negative Breast Cancers
NCT06190899PHASE1/PHASE2RECRUITINGGedatolisib in Combination With Darolutamide in Metastatic Castration-Resistant Prostate Cancer
NCT01420081PHASE2TERMINATEDA Study Of Two Dual PI3K/mTOR Inhibitors, PF-04691502 And PF-05212384 In Patients With Recurrent Endometrial Cancer
NCT01925274PHASE2TERMINATEDA Study Of PF-05212384 Plus Irinotecan Vs Cetuximab Plus Irinotecan In Patients With KRAS And NRAS Wild Type Metastatic Colorectal Cancer
NCT01937715PHASE1/PHASE2TERMINATEDA Study Of PF-05212384 Plus FOLFIRI Versus Bevacizumab Plus FOLFIRI In Metastatic Colorectal Cancer
NCT02438761PHASE2TERMINATEDPF-05212384 (PKI-587) for t-AML/MDS or de Novo Relapsed or Refractory Acute Myeloid Leukemia (AML) (LAM-PIK)
NCT02920450PHASE1/PHASE2TERMINATEDStudy of Paclitaxel, Carboplatin, and PF-05212384 in Advanced or Metastatic NSCLC (UF-STO-LUNG-002)
NCT03400254PHASE1/PHASE2WITHDRAWNGedatolisib, Hydroxychloroquine or the Combination for Prevention of Recurrent Breast Cancer (GLACIER)
NCT03698383PHASE2UNKNOWNPhase II Study of Herzuma® Plus Gedatolisib in Patients With HER-2 Positive Metastatic Breast Cancer
NCT01347866PHASE1TERMINATEDClinical Study Of PI3K/mTOR Inhibitors In Combination With An Oral MEK Inhibitor Or Irinotecan In Patients With Advanced Cancer
NCT01920061PHASE1COMPLETEDA Study Of PF-05212384 In Combination With Other Anti-Tumor Agents and in Combination With Cisplatin in Patients With Triple Negative Breast Cancer in an Expansion Arm (TNBC)
NCT02069158PHASE1COMPLETEDDose Finding Study Of PF-05212384 With Paclitaxel And Carboplatin In Patients With Advanced Solid Tumor
NCT02142920PHASE1COMPLETEDInvestigation Of The Metabolism, And Excretion Of [14c]-PF-05212384 In Healthy Male Volunteers
NCT02626507PHASE1UNKNOWNPhase I Study of Combination of Gedatolisib With Palbociclib and Faslodex in Patients With ER+/HER2- Breast Cancer
NCT02684032PHASE1COMPLETEDA Study To Assess The Tolerability And Clinical Activity Of Gedatolisib In Combination With Palbociclib/Letrozole Or Palbociclib/Fulvestrant In Women With Metastatic Breast Cancer
NCT03065062PHASE1SUSPENDEDStudy of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the PI3K/mTOR Inhibitor Gedatolisib (PF-05212384) for Patients With Advanced Squamous Cell Lung, Pancreatic, Head & Neck and Other Solid Tumors
NCT03243331PHASE1COMPLETEDAn Initial Safety Study of Gedatolisib Plus PTK7-ADC for Metastatic Triple-negative Breast Cancer
NCT05134922Not specifiedAVAILABLEExpanded Access Protocol for Subjects Previously Treated With Gedatolisib in B2151009

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.

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.

180 molecules share ≥1 primary target. Top 100 by shared-target count:

MoleculeSourceStatusShared targets
CrizotinibChEMBL + PubChemPhase 4 (approved)MTOR, PIK3CA
IdelalisibChEMBL + PubChemPhase 4 (approved)MTOR, PIK3CA
ALPELISIBChEMBLPhase 4 (approved)MTOR, PIK3CA
COPANLISIBChEMBLPhase 4 (approved)MTOR, PIK3CA
DASATINIBChEMBLPhase 4 (approved)MTOR, PIK3CA
BUPARLISIBChEMBLPhase 3MTOR, PIK3CA
DACTOLISIBChEMBLPhase 3MTOR, PIK3CA
EPIGALOCATECHIN GALLATEChEMBLPhase 3MTOR, PIK3CA
RESVERATROLChEMBLPhase 3MTOR, PIK3CA
TASELISIBChEMBLPhase 3MTOR, PIK3CA
APITOLISIBChEMBLPhase 2MTOR, PIK3CA
AZD-6482ChEMBLPhase 2MTOR, PIK3CA
BERZOSERTIBChEMBLPhase 2MTOR, PIK3CA
BGT-226 FREE BASEChEMBLPhase 2MTOR, PIK3CA
BIMIRALISIBChEMBLPhase 2MTOR, PIK3CA
CC-115ChEMBLPhase 2MTOR, PIK3CA
FIMEPINOSTATChEMBLPhase 2MTOR, PIK3CA
IZORLISIBChEMBLPhase 2MTOR, PIK3CA
OMIPALISIBChEMBLPhase 2MTOR, PIK3CA
ONATASERTIBChEMBLPhase 2MTOR, PIK3CA
OSI-027ChEMBLPhase 2MTOR, PIK3CA
PAXALISIBChEMBLPhase 2MTOR, PIK3CA
PF-04691502ChEMBLPhase 2MTOR, PIK3CA
PICTILISIBChEMBLPhase 2MTOR, PIK3CA
SAMOTOLISIBChEMBLPhase 2MTOR, PIK3CA
SAPANISERTIBChEMBLPhase 2MTOR, PIK3CA
SONOLISIBChEMBLPhase 2MTOR, PIK3CA
TG100-115ChEMBLPhase 2MTOR, PIK3CA
VISTUSERTIBChEMBLPhase 2MTOR, PIK3CA
VOXTALISIBChEMBLPhase 2MTOR, PIK3CA
ZSTK-474ChEMBLPhase 2MTOR, PIK3CA
AfatinibPubChemApprovedMTOR, PIK3CA
PazopanibPubChemApprovedMTOR, PIK3CA
SelumetinibPubChemApprovedMTOR, PIK3CA
AMIODARONEChEMBLPhase 4 (approved)MTOR
AMITRIPTYLINEChEMBLPhase 4 (approved)MTOR
AMOXAPINEChEMBLPhase 4 (approved)MTOR
AMSACRINEChEMBLPhase 4 (approved)MTOR
AZACITIDINEChEMBLPhase 4 (approved)MTOR
BELINOSTATChEMBLPhase 4 (approved)PIK3CA
BROMOCRIPTINEChEMBLPhase 4 (approved)MTOR
CARVEDILOLChEMBLPhase 4 (approved)MTOR
CHLOROQUINEChEMBLPhase 4 (approved)MTOR
CHLORPROMAZINEChEMBLPhase 4 (approved)MTOR
CLEMASTINEChEMBLPhase 4 (approved)MTOR
CLOMIPRAMINEChEMBLPhase 4 (approved)MTOR
CYCLOBENZAPRINEChEMBLPhase 4 (approved)MTOR
CYCLOSPORINEChEMBLPhase 4 (approved)MTOR
CYPROHEPTADINEChEMBLPhase 4 (approved)MTOR
CYTARABINEChEMBLPhase 4 (approved)MTOR
DEQUALINIUMChEMBLPhase 4 (approved)MTOR
DESIPRAMINEChEMBLPhase 4 (approved)MTOR
DISULFIRAMChEMBLPhase 4 (approved)MTOR
DOMPERIDONEChEMBLPhase 4 (approved)MTOR
DOPAMINEChEMBLPhase 4 (approved)MTOR
DOXAZOSINChEMBLPhase 4 (approved)MTOR
DUVELISIBChEMBLPhase 4 (approved)PIK3CA
EBASTINEChEMBLPhase 4 (approved)MTOR
EMETINEChEMBLPhase 4 (approved)MTOR
EPINEPHRINEChEMBLPhase 4 (approved)MTOR
EVEROLIMUSChEMBLPhase 4 (approved)MTOR
FEDRATINIBChEMBLPhase 4 (approved)PIK3CA
FELODIPINEChEMBLPhase 4 (approved)MTOR
FENOFIBRATEChEMBLPhase 4 (approved)MTOR
FLUOROURACILChEMBLPhase 4 (approved)MTOR
FLUOXETINEChEMBLPhase 4 (approved)MTOR
FLUPHENAZINEChEMBLPhase 4 (approved)MTOR
FLUSPIRILENEChEMBLPhase 4 (approved)MTOR
GUANABENZChEMBLPhase 4 (approved)MTOR
HALOPERIDOLChEMBLPhase 4 (approved)MTOR
HYDROQUINONEChEMBLPhase 4 (approved)MTOR
IDARUBICINChEMBLPhase 4 (approved)MTOR
IMIPRAMINEChEMBLPhase 4 (approved)MTOR
INAVOLISIBChEMBLPhase 4 (approved)PIK3CA
INDOMETHACINChEMBLPhase 4 (approved)MTOR
ISOPROTERENOLChEMBLPhase 4 (approved)MTOR
ISOTRETINOINChEMBLPhase 4 (approved)MTOR
LENIOLISIBChEMBLPhase 4 (approved)PIK3CA
LOPERAMIDEChEMBLPhase 4 (approved)MTOR
LORATADINEChEMBLPhase 4 (approved)MTOR
MAPROTILINEChEMBLPhase 4 (approved)MTOR
MASOPROCOLChEMBLPhase 4 (approved)MTOR
MEMANTINEChEMBLPhase 4 (approved)MTOR
METHYLDOPAChEMBLPhase 4 (approved)MTOR
MIBEFRADILChEMBLPhase 4 (approved)MTOR
MIDOSTAURINChEMBLPhase 4 (approved)PIK3CA
MIFEPRISTONEChEMBLPhase 4 (approved)MTOR
MITOXANTRONEChEMBLPhase 4 (approved)MTOR
NAFTOPIDILChEMBLPhase 4 (approved)MTOR
NICARDIPINEChEMBLPhase 4 (approved)MTOR
NICLOSAMIDEChEMBLPhase 4 (approved)MTOR
NIFEDIPINEChEMBLPhase 4 (approved)MTOR
NORTRIPTYLINEChEMBLPhase 4 (approved)MTOR
PACLITAXELChEMBLPhase 4 (approved)MTOR
PANCURONIUMChEMBLPhase 4 (approved)MTOR
PAROXETINEChEMBLPhase 4 (approved)MTOR
PENTAMIDINE ISETHIONATEChEMBLPhase 4 (approved)MTOR
PERPHENAZINEChEMBLPhase 4 (approved)MTOR
PIMOZIDEChEMBLPhase 4 (approved)MTOR
PRAZOSINChEMBLPhase 4 (approved)MTOR

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
v1.1.4
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