leniolisib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
phosphatidylinositol 3-kinase inhibitors, antineoplastics 5715 1354690-24-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • leniolisib
  • leniolisib phosphate
  • joenja
  • CDZ173-NX
  • CDZ-173
  • CDZ173
Leniolisib inhibits PI3K-delta by blocking the active binding site of PI3K-delta. In cell-free isolated enzyme assays, leniolisib was selective for PI3K-delta over PI3K-alpha (28-fold), PI3K-beta (43-fold), and PI3K-gamma (257-fold), as well as the broader kinome. In cell-based assays, leniolisib reduced pAKT pathway activity and inhibited proliferation and activation of B and T cell subsets. Gain-of-function variants in the gene encoding the p110-delta catalytic subunit or loss of function variants in the gene encoding the p85-alpha regulatory subunit each cause hyperactivity of PI3K-delta. Leniolisib inhibits the signalling pathways that lead to increased production of PIP3, hyperactivity of the downstream mTOR/AKT pathway, and to the dysregulation of B and T cells.
  • Molecular weight: 450.47
  • Formula: C21H25F3N6O2
  • CLOGP: 2.88
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 1
  • TPSA: 83.48
  • ALOGS:
  • ROTB: 6
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
kinase-safety-class EIF2AK3,GRK2,PDK1,PDK2,PDK4,PIK3CD,PRKDC 7
pfas-class PFAS structural alert (1 = True, 0 = False) 1

Approvals:

DateAgencyCompanyOrphan
March 24, 2023 FDA PHARMING

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

None

FDA Adverse Event Reporting System (Geriatric)

None

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L03AX22 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
IMMUNOSTIMULANTS
IMMUNOSTIMULANTS
Other immunostimulants
MeSH PA D000081082 Phosphoinositide-3 Kinase Inhibitors
MeSH PA D004791 Enzyme Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000182138 Cytochrome P450 1A2 Inhibitors
FDA MoA N0000190107 Organic Anion Transporting Polypeptide 1B1 Inhibitors
FDA MoA N0000190108 Organic Anion Transporting Polypeptide 1B3 Inhibitors
FDA MoA N0000190113 Breast Cancer Resistance Protein Inhibitors
FDA MoA N0000194054 Phosphoinositide 3-Kinase delta Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50846 immunomodulator
CHEBI has role CHEBI:229651 EC 2.7.1.153 (phosphatidylinositol-4,5-bisphosphate 3-kinase) inhibitor

Related Drugs by ATC class:

L03AX Other immunostimulants 15 drugs
cridanimodelapegademaseglatiramer acetatehistaminelentinanmavorixaformifamurtidemotixafortidepegademasepidotimodplerixaforroquinimex show all 15 →

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Activated PI3K delta syndrome (APDS) indication 711480000




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 70MG BASE JOENJA PHARMING N217759 March 24, 2023 RX TABLET ORAL March 24, 2028 NEW CHEMICAL ENTITY
EQ 70MG BASE JOENJA PHARMING N217759 March 24, 2023 RX TABLET ORAL March 24, 2030 TREATMENT OF ACTIVATED PHOSPHOINOSITIDE 3-KINASE DELTA (PI3K DELTA) SYNDROME (APDS) IN ADULT AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Kinase INHIBITOR IC50 7.25 DRUG LABEL DRUG LABEL
cAMP-specific 3',5'-cyclic phosphodiesterase 4D Enzyme IC50 5.33 CHEMBL
DNA-dependent protein kinase catalytic subunit Kinase IC50 6.06 CHEMBL
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Kinase IC50 6.04 CHEMBL
5-hydroxytryptamine receptor 2B GPCR IC50 5.11 CHEMBL
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Kinase INHIBITOR IC50 5.79 DRUG LABEL
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform Kinase INHIBITOR IC50 5.63 DRUG LABEL
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Kinase IC50 5.39 CHEMBL

External reference:

IDSource
CHEBI:229649 CHEBI
9NQ PDB_CHEM_ID
CHEMBL3643413 ChEMBL_ID
C000625376 MESH_SUPPLEMENTAL_RECORD_UI
9424 IUPHAR_LIGAND_ID
DB16217 DRUGBANK_ID
933450921000036101 SNOMEDCT_US
4042147 VANDF
C4547202 UMLSCUI
CHEMBL3989909 ChEMBL_ID
10255 INN_ID
1354691-97-6 SECONDARY_CAS_RN
57495353 PUBCHEM_CID
365867 MMSL
41353 MMSL
d10028 MMSL
019356 NDDF
019357 NDDF
D11158 KEGG_DRUG
L22772Z9CP UNII
2633005 RXNORM
L22772Z9CP INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Joenja HUMAN PRESCRIPTION DRUG LABEL 1 71274-170 TABLET, FILM COATED 70 mg ORAL NDA 29 sections