idelalisib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
phosphatidylinositol 3-kinase inhibitors, antineoplastics 4878 870281-82-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • CAL 101
  • idelalisib
  • zydelig
  • CAL-101
  • GS-1101
Idelalisib is an inhibitor of PI3K-delta kinase, which is expressed in normal and malignant B-cells. Idelalisib induced apoptosis and inhibited proliferation in cell lines derived from malignant B-cells and in primary tumor cells. Idelalisib inhibits several cell signaling pathways, including B-cell receptor (BCR) signaling and the CXCR4 and CXCR5 signaling, which are involved in trafficking and homing of B-cells to the lymph nodes and bone marrow.
  • Molecular weight: 415.43
  • Formula: C22H18FN7O
  • CLOGP: 3.62
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 2
  • TPSA: 99.16
  • ALOGS: -4.22
  • ROTB: 5

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
July 25, 2014 EMA
July 23, 2014 FDA GILEAD SCIENCES INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Disease progression 1049.80 33.48 343 2904 90957 46591858
Off label use 97.23 33.48 125 3122 379716 46303099
Chronic lymphocytic leukaemia 90.99 33.48 24 3223 2876 46679939
Diarrhoea 87.75 33.48 146 3101 559456 46123359
Death 86.64 33.48 111 3136 335437 46347378
Colitis 86.22 33.48 45 3202 37302 46645513
Pneumonitis 85.53 33.48 41 3206 28379 46654436
Cytomegalovirus infection 72.87 33.48 32 3215 18112 46664703
Non-small cell lung cancer 70.60 33.48 20 3227 3124 46679691
Neutropenia 67.36 33.48 65 3182 143139 46539676
Chronic lymphocytic leukaemia recurrent 49.01 33.48 9 3238 197 46682618
Lung disorder 44.41 33.48 31 3216 43273 46639542
Nonspecific reaction 42.58 33.48 12 3235 1838 46680977
Pyrexia 41.42 33.48 81 3166 348721 46334094
Pneumonia 40.65 33.48 84 3163 376236 46306579
Lymph node palpable 40.38 33.48 7 3240 109 46682706
Progressive multifocal leukoencephalopathy 39.13 33.48 18 3229 11328 46671487
Pseudolymphoma 39.01 33.48 9 3238 619 46682196
Chronic lymphocytic leukaemia refractory 38.38 33.48 6 3241 47 46682768
B-cell lymphoma recurrent 36.72 33.48 8 3239 424 46682391
B-cell lymphoma refractory 34.94 33.48 6 3241 88 46682727
Dehydration 33.61 33.48 48 3199 159492 46523323

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Disease progression 1439.49 28.46 542 5117 79332 29867487
Diarrhoea 209.10 28.46 283 5376 333820 29612999
Pneumonitis 178.42 28.46 92 5567 27362 29919457
Colitis 173.98 28.46 94 5565 30726 29916093
Off label use 97.97 28.46 171 5488 249119 29697700
Chronic lymphocytic leukaemia 91.43 28.46 34 5625 4594 29942225
Pneumonia 81.63 28.46 188 5471 334118 29612701
Chronic lymphocytic leukaemia recurrent 68.34 28.46 16 5643 422 29946397
Death 62.21 28.46 177 5482 357106 29589713
Lymphocytosis 56.13 28.46 19 5640 1951 29944868
Pyrexia 54.20 28.46 149 5510 294340 29652479
Neutropenia 49.94 28.46 88 5571 128452 29818367
Dehydration 47.24 28.46 84 5575 123455 29823364
Pneumocystis jirovecii infection 46.44 28.46 15 5644 1330 29945489
Lung disorder 46.17 28.46 42 5617 31427 29915392
Lymphoma transformation 41.81 28.46 9 5650 160 29946659
Febrile neutropenia 41.35 28.46 73 5586 106620 29840199
Electrolyte imbalance 40.76 28.46 26 5633 11474 29935345
Respiratory tract infection 33.74 28.46 26 5633 15480 29931339
Cytomegalovirus colitis 31.20 28.46 13 5646 2366 29944453
Mixed dementia 29.09 28.46 7 5652 208 29946611

Pharmacologic Action:

SourceCodeDescription
ATC L01EM01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Phosphatidylinositol-3-kinase (Pi3K) inhibitors
FDA MoA N0000175082 Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
FDA MoA N0000190114 Cytochrome P450 3A Inhibitors
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:50914 pi-3 kinase inhibitor
CHEBI has role CHEBI:68495 type i programmed cell-death inducer

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Chronic lymphoid leukemia, disease indication 92814006
Malignant lymphoma - small lymphocytic indication 302841002
Follicular non-Hodgkin's lymphoma indication 308121000
Toxic epidermal necrolysis due to drug contraindication 402744003

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 10.29 acidic
pKa2 4.22 Basic
pKa3 2.56 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
100MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL July 23, 2021 RELAPSED CLL, IN COMBO. WITH RITUXIMAB, IN PATIENTS FOR WHOM RITUXIMAB ALONE WOULD BE CONSIDERED APPROPRIATE THERAPY DUE TO OTHER CO-MORBIDITIES; AND RELAPSED SLL IN PATIENTS WHO HAVE RECEIVED AT LEAST 2 PRIOR SYSTEMIC THERAPIES
100MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL July 23, 2021 RELAPSED FOLLICULAR B-CELL NON-HODGKIN LYMPHOMA (FL) IN PATIENTS WHO HAVE RECEIVED AT LEAST TWO PRIOR SYSTEMIC THERAPIES
150MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL July 23, 2021 RELAPSED CLL, IN COMBO. WITH RITUXIMAB, IN PATIENTS FOR WHOM RITUXIMAB ALONE WOULD BE CONSIDERED APPROPRIATE THERAPY DUE TO OTHER CO-MORBIDITIES; AND RELAPSED SLL IN PATIENTS WHO HAVE RECEIVED AT LEAST 2 PRIOR SYSTEMIC THERAPIES
150MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL July 23, 2021 RELAPSED FOLLICULAR B-CELL NON-HODGKIN LYMPHOMA (FL) IN PATIENTS WHO HAVE RECEIVED AT LEAST TWO PRIOR SYSTEMIC THERAPIES

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Kinase INHIBITOR IC50 8.60 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Kinase IC50 7.05 SCIENTIFIC LITERATURE
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform Kinase IC50 6.25 SCIENTIFIC LITERATURE
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Kinase IC50 6.09 SCIENTIFIC LITERATURE
DNA-dependent protein kinase catalytic subunit Kinase IC50 5.17 CHEMBL

External reference:

IDSource
D10560 KEGG_DRUG
4033559 VUID
N0000190926 NUI
4033559 VANDF
C2703131 UMLSCUI
CHEBI:82701 CHEBI
40L PDB_CHEM_ID
CHEMBL2216870 ChEMBL_ID
DB09054 DRUGBANK_ID
C552946 MESH_SUPPLEMENTAL_RECORD_UI
11625818 PUBCHEM_CID
6741 IUPHAR_LIGAND_ID
9624 INN_ID
YG57I8T5M0 UNII
1544460 RXNORM
226727 MMSL
30429 MMSL
d08273 MMSL
015626 NDDF
709283009 SNOMEDCT_US
710278000 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Zydelig HUMAN PRESCRIPTION DRUG LABEL 1 61958-1701 TABLET, FILM COATED 100 mg ORAL NDA 33 sections
Zydelig HUMAN PRESCRIPTION DRUG LABEL 1 61958-1702 TABLET, FILM COATED 150 mg ORAL NDA 33 sections