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Leniolisib

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Also known as Cdz-173 free baseCdz173 free baseCDZ-173CDZ173LENIOLISIB (CDZ 173)US8653092, 67

Summary

Leniolisib (CHEMBL3643413) is an approved small-molecule EC 2.7.1.153 (phosphatidylinositol-4,5-bisphosphate 3-kinase) inhibitor (ATC L03AX22) targeting PIK3CA and PIK3CD; indicated across 1 condition including neoplasm.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: L03AX22
  • Targets: 2 (PIK3CA, PIK3CD)
  • Indications: 1 condition
  • Clinical trials: 9
  • Chemistry: 450.5 Da · C21H25F3N6O2

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL3643413
NameLeniolisib
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID57495353
ChEBICHEBI:229649
ATCL03AX22
Molecular formulaC21H25F3N6O2
Molecular weight450.5
InChIKeyMWKYMZXCGYXLPL-ZDUSSCGKSA-N

SMILES: CCC(=O)N1CC[C@@H](C1)NC2=NC=NC3=C2CN(CC3)C4=CC(=C(N=C4)OC)C(F)(F)F

IUPAC name: 1-[(3S)-3-[[6-[6-methoxy-5-(trifluoromethyl)-3-pyridinyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-4-yl]amino]pyrrolidin-1-yl]propan-1-one

ChEBI definition: A pyridopyrimidine that is 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine substituted by [(3S)-1-propanoylpyrrolidin-3-yl]amino and 6-methoxy-5-(trifluoromethyl)pyridin-3-yl groups at positions 4 and 6, respectively.

Pharmacological roles (ChEBI): EC 2.7.1.153 (phosphatidylinositol-4,5-bisphosphate 3-kinase) inhibitor, immunomodulator.

Also known as: Cdz-173 free base, Cdz173 free base, Leniolisib, LENIOLISIB, CDZ-173, CDZ-173 FREE BASE, CDZ173 FREE BASE, CDZ173, LENIOLISIB (CDZ 173), US8653092, 67, leniolisib

Parent form; salt/anhydrous children: CHEMBL3989909

Patent coverage: 152 distinct patent families (341 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 302 (89%) 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 alphaInhibition6.5842.7%P42336
PIK3CDphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit deltaInhibition7.646%O00329

Broader ChEMBL bioactivity targets: 10 (assay-derived). Sample: 5-hydroxytryptamine receptor 2B, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, 3’,5’-cyclic-AMP phosphodiesterase 4D, 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, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform.

Bioactivity

ChEMBL activities: 45 potent at pChembl ≥ 5 of 46 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
PIK3CD8.82IC501.5nMCHEMBL_ACT_24925466
O359048.15IC507nMCHEMBL_ACT_18320275
O359048IC5010nMCHEMBL_ACT_18320287
PIK3CD7.96IC5011nMCHEMBL_ACT_18320214
PIK3CD7.96IC5011nMCHEMBL_ACT_25755825
PIK3CD7.96IC5011nMCHEMBL_ACT_29055479
PIK3CD7.96IC5011nMCHEMBL_ACT_29231728
PIK3CD7.64IC5023nMCHEMBL_ACT_16259739
O359047.48IC5033nMCHEMBL_ACT_18320286
O359047.32IC5048nMCHEMBL_ACT_18320262
PIK3CD7.25IC5056nMCHEMBL_ACT_18320250
PIK3CD7.25IC5056nMCHEMBL_ACT_25755072
PIK3CD7.2IC5062.8nMCHEMBL_ACT_24925525
PIK3CD7.14IC5073nMCHEMBL_ACT_18320284
PIK3CA7.12IC5075.5nMCHEMBL_ACT_24925436
PIK3CD7.1IC5079nMCHEMBL_ACT_18320281
PIK3CD7.02IC5095nMCHEMBL_ACT_18320283
O359047IC50101nMCHEMBL_ACT_18320288
PIK3CD6.84IC50144nMCHEMBL_ACT_18320276
PIK3CD6.8IC50159nMCHEMBL_ACT_18320282
PIK3CD6.71IC50193nMCHEMBL_ACT_18320278
PIK3CD6.7IC50202nMCHEMBL_ACT_18320277
PIK3CA6.61IC50244nMCHEMBL_ACT_18320178
PIK3CA6.61IC50244nMCHEMBL_ACT_29055475
PIK3CA6.61IC50244nMCHEMBL_ACT_29231725
PIK3CA6.58IC50262nMCHEMBL_ACT_16346648
PIK3CB6.44IC50363nMCHEMBL_ACT_24925513
PIK3CB6.37IC50424nMCHEMBL_ACT_18320190
PIK3CB6.37IC50424nMCHEMBL_ACT_29055477
PIK3CB6.37IC50424nMCHEMBL_ACT_29231726

Target pathways

Aggregated over 2 target gene(s): PIK3CA, PIK3CD.

Top Reactome pathways

61 total, by targets touching each:

PathwayTargetsGenes
PIP3 activates AKT signaling2PIK3CA, PIK3CD
Synthesis of PIPs at the plasma membrane2PIK3CA, PIK3CD
Constitutive Signaling by Aberrant PI3K in Cancer2PIK3CA, PIK3CD
CD28 dependent PI3K/Akt signaling2PIK3CA, PIK3CD
Interleukin-3, Interleukin-5 and GM-CSF signaling2PIK3CA, PIK3CD
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling2PIK3CA, PIK3CD
RET signaling2PIK3CA, PIK3CD
Erythropoietin activates Phosphoinositide-3-kinase (PI3K)2PIK3CA, PIK3CD
Interleukin receptor SHC signaling2PIK3CA, PIK3CD
Regulation of signaling by CBL2PIK3CA, PIK3CD
Signaling by CSF1 (M-CSF) in myeloid cells2PIK3CA, PIK3CD
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells2PIK3CA, PIK3CD
Co-stimulation by ICOS2PIK3CA, PIK3CD
PI3K Cascade1PIK3CA
IRS-mediated signalling1PIK3CA
GPVI-mediated activation cascade1PIK3CA
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants1PIK3CA
PI3K events in ERBB4 signaling1PIK3CA
Signaling by SCF-KIT1PIK3CA
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
DAP12 signaling1PIK3CA
Role of LAT2/NTAL/LAB on calcium mobilization1PIK3CA

Dominant GO biological processes

GO termTargets
cell migration2
phosphatidylinositol-3-phosphate biosynthetic process2
vascular endothelial growth factor signaling pathway2
phosphatidylinositol 3-kinase/protein kinase B signal transduction2
phosphatidylinositol phosphate biosynthetic process2
phosphatidylinositol-mediated signaling2
T cell receptor signaling pathway2
lipid metabolic process2
angiogenesis1
liver development1
vasculature development1
glucose metabolic process1
phagocytosis1
epidermal growth factor receptor signaling pathway1
insulin receptor signaling pathway1

Indications & clinical

Indications

1 indication (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
neoplasm3MONDO:0005070EFO:0000616

Clinical trials

Total trials: 9.

Phase distribution

PhaseTrials
PHASE24
PHASE33
PHASE2/PHASE32

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05438407PHASE3ACTIVE_NOT_RECRUITINGPediatric Patients Aged 4 to 11 Years With APDS
NCT05693129PHASE3ACTIVE_NOT_RECRUITINGPediatric Patients Aged 1 to 6 Years With APDS
NCT02435173PHASE2/PHASE3COMPLETEDStudy of Efficacy of CDZ173 in Patients With APDS/PASLI
NCT02859727PHASE2/PHASE3TERMINATEDExtension to the Study of Efficacy of CDZ173 in Patients With APDS/PASLI
NCT06249997PHASE3UNKNOWNAn Open-Label Study to Assess the Safety & Efficacy of Leniolisib in Japanese Patients With APDS
NCT06549114PHASE2ACTIVE_NOT_RECRUITINGLeniolisib for Immune Dysregulation in PIDs
NCT06897358PHASE2ACTIVE_NOT_RECRUITINGLeniolisib for Immune Dysregulation in CVID
NCT06990529PHASE2RECRUITINGLong-term Safety and Efficacy of Leniolisib in PIDs With Immune Dysregulation
NCT02775916PHASE2COMPLETEDSafety, Pharmacokinetics, and Preliminary Efficacy Study of CDZ173 in Patients With Primary Sjögren’s Syndrome

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.

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

MoleculeSourceStatusShared targets
CRIZOTINIBChEMBL + PubChemPhase 4 (approved)PIK3CA, PIK3CD
IDELALISIBChEMBL + PubChemPhase 4 (approved)PIK3CA, PIK3CD
INAVOLISIBChEMBL + PubChemPhase 4 (approved)PIK3CA, PIK3CD
ALPELISIBChEMBLPhase 4 (approved)PIK3CA, PIK3CD
COPANLISIBChEMBLPhase 4 (approved)PIK3CA, PIK3CD
DASATINIBChEMBLPhase 4 (approved)PIK3CA, PIK3CD
DUVELISIBChEMBLPhase 4 (approved)PIK3CA, PIK3CD
SUNITINIBChEMBLPhase 4 (approved)PIK3CA, PIK3CD
BUPARLISIBChEMBLPhase 3PIK3CA, PIK3CD
DACTOLISIBChEMBLPhase 3PIK3CA, PIK3CD
GEDATOLISIBChEMBLPhase 3PIK3CA, PIK3CD
LESTAURTINIBChEMBLPhase 3PIK3CA, PIK3CD
TASELISIBChEMBLPhase 3PIK3CA, PIK3CD
AMG-319ChEMBLPhase 2PIK3CA, PIK3CD
APITOLISIBChEMBLPhase 2PIK3CA, PIK3CD
AZD-6482ChEMBLPhase 2PIK3CA, PIK3CD
AZD-8154ChEMBLPhase 2PIK3CA, PIK3CD
BGT-226 FREE BASEChEMBLPhase 2PIK3CA, PIK3CD
BI-2536ChEMBLPhase 2PIK3CA, PIK3CD
BIMIRALISIBChEMBLPhase 2PIK3CA, PIK3CD
EGANELISIBChEMBLPhase 2PIK3CA, PIK3CD
FIMEPINOSTATChEMBLPhase 2PIK3CA, PIK3CD
IZORLISIBChEMBLPhase 2PIK3CA, PIK3CD
NEMIRALISIBChEMBLPhase 2PIK3CA, PIK3CD
OMIPALISIBChEMBLPhase 2PIK3CA, PIK3CD
ONATASERTIBChEMBLPhase 2PIK3CA, PIK3CD
PAXALISIBChEMBLPhase 2PIK3CA, PIK3CD
PF-04691502ChEMBLPhase 2PIK3CA, PIK3CD
PICTILISIBChEMBLPhase 2PIK3CA, PIK3CD
PILARALISIBChEMBLPhase 2PIK3CA, PIK3CD
QUISINOSTATChEMBLPhase 2PIK3CA, PIK3CD
RISOVALISIBChEMBLPhase 2PIK3CA, PIK3CD
ROGINOLISIBChEMBLPhase 2PIK3CA, PIK3CD
SAMOTOLISIBChEMBLPhase 2PIK3CA, PIK3CD
SAPANISERTIBChEMBLPhase 2PIK3CA, PIK3CD
SERABELISIBChEMBLPhase 2PIK3CA, PIK3CD
SONOLISIBChEMBLPhase 2PIK3CA, PIK3CD
TG100-115ChEMBLPhase 2PIK3CA, PIK3CD
VISTUSERTIBChEMBLPhase 2PIK3CA, PIK3CD
VOXTALISIBChEMBLPhase 2PIK3CA, PIK3CD
ZSTK-474ChEMBLPhase 2PIK3CA, PIK3CD
AfatinibPubChemApprovedPIK3CA, PIK3CD
PazopanibPubChemApprovedPIK3CA, PIK3CD
SelumetinibPubChemApprovedPIK3CA, PIK3CD
BELINOSTATChEMBLPhase 4 (approved)PIK3CA
CAFFEINEChEMBLPhase 4 (approved)PIK3CD
FEDRATINIBChEMBLPhase 4 (approved)PIK3CA
MIDOSTAURINChEMBLPhase 4 (approved)PIK3CA
ROMIDEPSINChEMBLPhase 4 (approved)PIK3CA
THEOPHYLLINEChEMBLPhase 4 (approved)PIK3CD
UMBRALISIBChEMBLPhase 4 (approved)PIK3CD
EPIGALOCATECHIN GALLATEChEMBLPhase 3PIK3CA
IPATASERTIBChEMBLPhase 3PIK3CA
PARSACLISIBChEMBLPhase 3PIK3CD
POVORCITINIBChEMBLPhase 3PIK3CD
RESVERATROLChEMBLPhase 3PIK3CA
ACALISIBChEMBLPhase 2PIK3CD
AMDIZALISIBChEMBLPhase 2PIK3CD
BERZOSERTIBChEMBLPhase 2PIK3CA
CC-115ChEMBLPhase 2PIK3CA

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 29

This page pulls from 29 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot