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 1528.87 68.05 325 928 16770 2340062
Diarrhoea 286.06 68.05 132 1121 83432 2273400
Off label use 250.41 68.05 116 1137 73482 2283350
Death 200.21 68.05 103 1150 81365 2275467
Pneumonia 161.29 68.05 76 1177 49220 2307612
Pneumonitis 157.19 68.05 40 1213 3999 2352833
Neutropenia 153.89 68.05 58 1195 21490 2335342
Colitis 137.66 68.05 38 1215 5188 2351644
Pyrexia 125.61 68.05 66 1187 53642 2303190
Cytomegalovirus infection 116.04 68.05 29 1224 2684 2354148
Chronic lymphocytic leukaemia 104.16 68.05 20 1233 535 2356297
Dehydration 103.27 68.05 44 1209 22251 2334581
Lung disorder 100.69 68.05 31 1222 6181 2350651
Non-small cell lung cancer 85.22 68.05 17 1236 556 2356276
Respiratory tract infection 69.03 68.05 21 1232 4008 2352824

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 2082.86 58.88 510 1654 16753 1727864
Diarrhoea 601.97 58.88 266 1898 53586 1691031
Pneumonia 327.40 58.88 168 1996 46014 1698603
Pneumonitis 316.76 58.88 86 2078 3829 1740788
Colitis 315.81 58.88 87 2077 4093 1740524
Off label use 310.23 58.88 153 2011 38418 1706199
Pyrexia 191.77 58.88 119 2045 46281 1698336
Death 190.20 58.88 151 2013 87292 1657325
Dehydration 161.80 58.88 77 2087 17581 1727036
Febrile neutropenia 154.81 58.88 65 2099 11035 1733582
Neutropenia 138.42 58.88 70 2094 18190 1726427
Lung disorder 109.89 58.88 41 2123 5078 1739539
Chronic lymphocytic leukaemia 98.22 58.88 25 2139 851 1743766
Sepsis 98.21 58.88 57 2107 19381 1725236
Electrolyte imbalance 85.22 58.88 25 2139 1456 1743161
Lymphocytosis 72.15 58.88 17 2147 416 1744201
Chronic lymphocytic leukaemia recurrent 71.76 58.88 13 2151 79 1744538
Respiratory tract infection 68.54 58.88 24 2140 2469 1742148
Drug ineffective 65.22 58.88 73 2091 63728 1680889
Cough 63.32 58.88 43 2121 19154 1725463
Hepatocellular injury 62.47 58.88 24 2140 3207 1741410
Acute kidney injury 61.80 58.88 54 2110 34890 1709727
Pneumocystis jirovecii infection 61.72 58.88 14 2150 288 1744329
Renal failure 61.69 58.88 43 2121 19974 1724643
Pneumocystis jirovecii pneumonia 61.27 58.88 22 2142 2434 1742183

Pharmacologic Action:

SourceCodeDescription
ATC L01XX47 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Other antineoplastic agents
CHEBI has role CHEBI:35610 antineoplastic agent
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000175082 Kinase Inhibitors
FDA MoA N0000190114 Cytochrome P450 3A Inhibitors

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)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
100MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL 6800620 April 24, 2021 A METHOD OF DISRUPTING LEUKOCYTE FUNCTION, INCLUDING AS AN INHIBITOR OF PI3KDELTA KINASE
100MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL 6949535 April 24, 2021 A METHOD OF DISRUPTING LEUKOCYTE FUNCTION, INCLUDING AS AN INHIBITOR OF PI3KDELTA KINASE
100MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL 8138195 April 24, 2021 FOR THE TREATMENT OF PATIENTS WITH RELAPSED CHRONIC LYMPHOCYTIC LEUKEMIA
150MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL 6800620 April 24, 2021 A METHOD OF DISRUPTING LEUKOCYTE FUNCTION, INCLUDING AS AN INHIBITOR OF PI3KDELTA KINASE
150MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL 6949535 April 24, 2021 A METHOD OF DISRUPTING LEUKOCYTE FUNCTION, INCLUDING AS AN INHIBITOR OF PI3KDELTA KINASE
150MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL 8138195 April 24, 2021 FOR THE TREATMENT OF PATIENTS WITH RELAPSED CHRONIC LYMPHOCYTIC LEUKEMIA
100MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL 8980901 May 12, 2025 FOR THE TREATMENT OF PATIENTS WITH CLL, FL, OR SLL
100MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL 9149477 May 12, 2025 INHIBITION ON PI3K KINASE
150MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL 8980901 May 12, 2025 FOR THE TREATMENT OF PATIENTS WITH CLL, FL, OR SLL
150MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL 9149477 May 12, 2025 INHIBITION ON PI3K KINASE
100MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL RE44599 July 21, 2025 FOR THE TREATMENT OF PATIENTS WITH CLL, FL, OR SLL
100MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL RE44599 July 21, 2025 FOR THE TREATMENT OF PATIENTS WITH RELAPSED FOLLICULAR B-CELL NON-HODGKIN LYMPHOMA OR [RELAPSED] SMALL LYMPHOCYTIC LYMPHOMA
150MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL RE44599 July 21, 2025 FOR THE TREATMENT OF PATIENTS WITH CLL, FL, OR SLL
150MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL RE44599 July 21, 2025 FOR THE TREATMENT OF PATIENTS WITH RELAPSED FOLLICULAR B-CELL NON-HODGKIN LYMPHOMA OR [RELAPSED] SMALL LYMPHOCYTIC LYMPHOMA
100MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL 9492449 March 11, 2030 IN COMBINATION WITH RITUXIMAB, FOR THE TREATMENT OF PATIENTS WITH RELAPSED CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)
150MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL 9492449 March 11, 2030 IN COMBINATION WITH RITUXIMAB, FOR THE TREATMENT OF PATIENTS WITH RELAPSED CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)
100MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL 8865730 March 5, 2033 FOR THE TREATMENT OF PATIENTS WITH CLL, FL, OR SLL
150MG ZYDELIG GILEAD SCIENCES INC N205858 July 23, 2014 RX TABLET ORAL 8865730 March 5, 2033 FOR THE TREATMENT OF PATIENTS WITH CLL, FL, OR SLL

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
C2698692 UMLSCUI
709283009 SNOMEDCT_US
1544460 RXNORM
015626 NDDF
30429 MMSL
d08273 MMSL
4033559 VANDF
710278000 SNOMEDCT_US
11625818 PUBCHEM_CID
CHEBI:82701 CHEBI
DB09054 DRUGBANK_ID
YG57I8T5M0 UNII
9624 INN_ID
CHEMBL2216870 ChEMBL_ID
6741 IUPHAR_LIGAND_ID
C552946 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Zydelig HUMAN PRESCRIPTION DRUG LABEL 1 61958-1701 TABLET, FILM COATED 100 mg ORAL NDA 19 sections
Zydelig HUMAN PRESCRIPTION DRUG LABEL 1 61958-1702 TABLET, FILM COATED 150 mg ORAL NDA 19 sections