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Atlas / Drug / Zandelisib

Zandelisib

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Also known as ACC-524Me-401PW-143Pwt-143PWT143

Summary

Zandelisib (CHEMBL4650214) is a phase-3 clinical-stage small molecule targeting MTOR, PIK3CA, and PIK3CB; indicated across 7 conditions including neoplasm of mature b-cells and follicular lymphoma.

At a glance

  • Status: Max clinical phase 3 (not approved)
  • Modality: Small molecule
  • Targets: 5 (MTOR, PIK3CA, PIK3CB…)
  • Indications: 7 conditions
  • Clinical trials: 9
  • Chemistry: 576.7 Da · C31H38F2N8O

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL4650214
NameZandelisib
TypeSmall molecule
Max phase3
FDA approvedno
PubChem CID66571003
Molecular formulaC31H38F2N8O
Molecular weight576.7
InChIKeyWPFUFWIHMYZXSF-UHFFFAOYSA-N

SMILES: CC(C)(CC1=CC=CC=C1C2CCN(CC2)C)NC3=NC(=NC(=N3)N4CCOCC4)N5C6=CC=CC=C6N=C5C(F)F

IUPAC name: 4-[2-(difluoromethyl)benzimidazol-1-yl]-N-[2-methyl-1-[2-(1-methylpiperidin-4-yl)phenyl]propan-2-yl]-6-morpholin-4-yl-1,3,5-triazin-2-amine

Also known as: ACC-524, Me-401, ME-401, PW-143, Pwt-143, PWT-143, PWT143, Zandelisib, ZANDELISIB

Patent coverage: 215 distinct patent families (529 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 491 (93%) 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
MTORmechanistic target of rapamycin kinaseInhibition6.398.3% (common-essential)P42345
PIK3CAphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alphaInhibition6.342.7%P42336
PIK3CBphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit betaInhibition6.75%P42338
PIK3CDphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit deltaInhibition76%O00329
PIK3CGphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gammaInhibition6.30.7%P48736

Bioactivity

No ChEMBL bioactivity rows at pChembl ≥ 5 (expected for biologics / antibodies).

Target pathways

Aggregated over 5 target gene(s): MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG.

Top Reactome pathways

99 total, by targets touching each:

PathwayTargetsGenes
PIP3 activates AKT signaling5MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
CD28 dependent PI3K/Akt signaling5MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
Synthesis of PIPs at the plasma membrane4PIK3CA, PIK3CB, PIK3CD, PIK3CG
Constitutive Signaling by Aberrant PI3K in Cancer4PIK3CA, PIK3CB, PIK3CD, PIK3CG
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling4PIK3CA, PIK3CB, PIK3CD, PIK3CG
Erythropoietin activates Phosphoinositide-3-kinase (PI3K)4PIK3CA, PIK3CB, PIK3CD, PIK3CG
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells4MTOR, PIK3CA, PIK3CB, PIK3CD
Co-stimulation by ICOS4PIK3CA, PIK3CB, PIK3CD, PIK3CG
GPVI-mediated activation cascade3PIK3CA, PIK3CB, PIK3CG
VEGFA-VEGFR2 Pathway3MTOR, PIK3CA, PIK3CB
Interleukin-3, Interleukin-5 and GM-CSF signaling3PIK3CA, PIK3CB, PIK3CD
RET signaling3PIK3CA, PIK3CB, PIK3CD
Interleukin receptor SHC signaling3PIK3CA, PIK3CB, PIK3CD
Regulation of signaling by CBL3PIK3CA, PIK3CB, PIK3CD
Signaling by CSF1 (M-CSF) in myeloid cells3PIK3CA, PIK3CB, PIK3CD
PI3K Cascade2PIK3CA, PIK3CB
IRS-mediated signalling2PIK3CA, PIK3CB
Downstream signal transduction2PIK3CA, PIK3CB
PI3K/AKT activation2PIK3CA, PIK3CB
Signaling by ALK2PIK3CA, PIK3CB
Downstream TCR signaling2PIK3CA, PIK3CB
Role of phospholipids in phagocytosis2PIK3CA, PIK3CB
Tie2 Signaling2PIK3CA, PIK3CB
DAP12 signaling2PIK3CA, PIK3CB
Role of LAT2/NTAL/LAB on calcium mobilization2PIK3CA, PIK3CB
Nephrin family interactions2PIK3CA, PIK3CB
RAF/MAP kinase cascade2PIK3CA, PIK3CB
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants2PIK3CA, PIK3CB
Signaling by PDGFRA extracellular domain mutants2PIK3CA, PIK3CB
Signaling by ALK fusions and activated point mutants2PIK3CA, PIK3CB

Dominant GO biological processes

GO termTargets
phosphatidylinositol 3-kinase/protein kinase B signal transduction5
cell migration4
phosphatidylinositol-3-phosphate biosynthetic process4
phosphatidylinositol phosphate biosynthetic process4
phosphatidylinositol-mediated signaling4
lipid metabolic process4
inflammatory response3
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction3
chemotaxis3
positive regulation of endothelial cell migration3
innate immune response3
positive regulation of lamellipodium assembly2
negative regulation of macroautophagy2
T cell costimulation2
cellular response to insulin stimulus2

Indications & clinical

Indications

7 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
neoplasm of mature B-cells3MONDO:0004949EFO:0000096
follicular lymphoma3MONDO:0018906MONDO:0018906
B-cell chronic lymphocytic leukemia2MONDO:0004948EFO:0000095
diffuse large B-cell lymphoma1MONDO:0018905EFO:0000403
mantle cell lymphoma1MONDO:0018876EFO:1001469
neoplasm1MONDO:0005070MONDO:0004992
B-cell acute lymphoblastic leukemia1MONDO:0004947EFO:0000094

Clinical trials

Total trials: 9.

Phase distribution

PhaseTrials
PHASE23
PHASE13
PHASE1/PHASE22
PHASE31

Top trials by phase / activity

NCTPhaseStatusTitle
NCT04745832PHASE3TERMINATEDPhase 3 Study of Zandelisib (ME-401) in Combination With Rituximab in Patients With iNHL - (COASTAL)
NCT04533581PHASE2ACTIVE_NOT_RECRUITINGStudy of ME-401 in Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin’s Lymphoma (NHL)
NCT03768505PHASE2TERMINATEDZandelisib (ME-401) in Subjects With Follicular Lymphoma or Marginal Zone Lymphoma After Failure of Two or More Prior Therapies (TIDAL)
NCT04517435PHASE1/PHASE2TERMINATEDME-401 and R-CHOP in Newly Diagnosed Diffuse Large B-Cell Lymphoma
NCT05209308PHASE2WITHDRAWNRituximab Plus Venetoclax in Combination With Zandelisib in Subjects With CLL
NCT05604417PHASE1/PHASE2WITHDRAWNZandelisib + Tazemetostat in R/R Follicular Lymphoma
NCT02521389PHASE1COMPLETEDAssessment of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Various Formulations and Doses of PWT-143
NCT02914938PHASE1TERMINATEDA Study of ME-401 in Subjects With CLL/SLL, FL, and B-cell Non Hodgkin’s Lymphoma
NCT03985189PHASE1COMPLETEDStudy of ME-401 in Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin’s Lymphoma

Clinical evidence (CIViC)

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

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.

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

MoleculeSourceStatusShared targets
CrizotinibChEMBL + PubChemPhase 4 (approved)MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
IdelalisibChEMBL + PubChemPhase 4 (approved)MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
ALPELISIBChEMBLPhase 4 (approved)MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
COPANLISIBChEMBLPhase 4 (approved)MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
BUPARLISIBChEMBLPhase 3MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
DACTOLISIBChEMBLPhase 3MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
GEDATOLISIBChEMBLPhase 3MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
TASELISIBChEMBLPhase 3MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
APITOLISIBChEMBLPhase 2MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
AZD-6482ChEMBLPhase 2MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
BGT-226 FREE BASEChEMBLPhase 2MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
BIMIRALISIBChEMBLPhase 2MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
FIMEPINOSTATChEMBLPhase 2MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
IZORLISIBChEMBLPhase 2MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
OMIPALISIBChEMBLPhase 2MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
ONATASERTIBChEMBLPhase 2MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
PAXALISIBChEMBLPhase 2MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
PF-04691502ChEMBLPhase 2MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
PICTILISIBChEMBLPhase 2MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
SAMOTOLISIBChEMBLPhase 2MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
SAPANISERTIBChEMBLPhase 2MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
TG100-115ChEMBLPhase 2MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
VISTUSERTIBChEMBLPhase 2MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
VOXTALISIBChEMBLPhase 2MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
ZSTK-474ChEMBLPhase 2MTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
AfatinibPubChemApprovedMTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
PazopanibPubChemApprovedMTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
SelumetinibPubChemApprovedMTOR, PIK3CA, PIK3CB, PIK3CD, PIK3CG
INAVOLISIBChEMBL + PubChemPhase 4 (approved)PIK3CA, PIK3CB, PIK3CD, PIK3CG
DUVELISIBChEMBLPhase 4 (approved)PIK3CA, PIK3CB, PIK3CD, PIK3CG
LENIOLISIBChEMBLPhase 4 (approved)PIK3CA, PIK3CB, PIK3CD, PIK3CG
LESTAURTINIBChEMBLPhase 3PIK3CA, PIK3CB, PIK3CD, PIK3CG
AMG-319ChEMBLPhase 2PIK3CA, PIK3CB, PIK3CD, PIK3CG
EGANELISIBChEMBLPhase 2PIK3CA, PIK3CB, PIK3CD, PIK3CG
NEMIRALISIBChEMBLPhase 2PIK3CA, PIK3CB, PIK3CD, PIK3CG
PILARALISIBChEMBLPhase 2PIK3CA, PIK3CB, PIK3CD, PIK3CG
ROGINOLISIBChEMBLPhase 2PIK3CA, PIK3CB, PIK3CD, PIK3CG
SERABELISIBChEMBLPhase 2PIK3CA, PIK3CB, PIK3CD, PIK3CG
SONOLISIBChEMBLPhase 2MTOR, PIK3CA, PIK3CD, PIK3CG
GefitinibPubChemApprovedMTOR, PIK3CB, PIK3CD, PIK3CG
DASATINIBChEMBLPhase 4 (approved)MTOR, PIK3CA, PIK3CD
SUNITINIBChEMBLPhase 4 (approved)PIK3CA, PIK3CD, PIK3CG
RESVERATROLChEMBLPhase 3MTOR, PIK3CA, PIK3CB
DEZAPELISIBChEMBLPhase 2PIK3CB, PIK3CD, PIK3CG
OSI-027ChEMBLPhase 2MTOR, PIK3CA, PIK3CG
QUISINOSTATChEMBLPhase 2PIK3CA, PIK3CB, PIK3CD
RISOVALISIBChEMBLPhase 2PIK3CA, PIK3CB, PIK3CD
FEDRATINIBChEMBLPhase 4 (approved)PIK3CA, PIK3CG
UMBRALISIBChEMBLPhase 4 (approved)PIK3CD, PIK3CG
EPIGALOCATECHIN GALLATEChEMBLPhase 3MTOR, PIK3CA
ACALISIBChEMBLPhase 2PIK3CD, PIK3CG
AMDIZALISIBChEMBLPhase 2PIK3CD, PIK3CG
AZD-8154ChEMBLPhase 2PIK3CA, PIK3CD
BERZOSERTIBChEMBLPhase 2MTOR, PIK3CA
BI-2536ChEMBLPhase 2PIK3CA, PIK3CD
CC-115ChEMBLPhase 2MTOR, PIK3CA
GSK-2636771ChEMBLPhase 2PIK3CB, PIK3CD
SELETALISIBChEMBLPhase 2PIK3CD, PIK3CG
TENALISIBChEMBLPhase 2PIK3CD, PIK3CG
AMIODARONEChEMBLPhase 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
v1.1.2
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