idelalisib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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: 3.32
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 2
  • TPSA: 99.16
  • ALOGS: -4.22
  • ROTB: 5
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.30 g O

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.582 Moderate 0.76
caco2-efflux Caco-2 efflux ratio (BA/AB) 7.396 Moderate 0.76
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 40.551 10^-6 cm/s Moderate 0.76
dh-clint Dog hepatocyte intrinsic clearance 2.911 uL/min/10^6 cells Moderate 0.76
dppb Dog plasma protein binding (% unbound) 14.520 % Moderate 0.76
fcs-ppb Fetal calf serum protein binding (% unbound) 32.930 % Moderate 0.76
herg hERG pIC50 4.485 pIC50 Moderate 0.76
hh-clint Human hepatocyte intrinsic clearance 4.027 uL/min/10^6 cells Moderate 0.76
hlm-clint Human liver microsomal intrinsic clearance 14.894 uL/min/mg protein Moderate 0.76
hppb Human plasma protein binding (% unbound) 11.890 % Moderate 0.76
kinase-safety-class ACVR2A,ACVR2B,AXL,BRAF,CAMK2B,CAMK2D,CDK5,CDK9,DDR1,DYRK1B,EGFR,EIF2AK3,ERBB2,FLT3,GRK2,ITK,MAP3K21,MAPK10,MAPK7,MARK4,MET,PDK2,PDK4,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PRKDC,SIK2,SIK3,STK33,TTK 32
kinase-selectivity-class AXL,ERBB2,GRK2,MAP3K21,PIK3CB,PIK3CD,PIK3CG 7
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 10.666 Moderate 0.76
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 20.749 Moderate 0.76
mh-clint Mouse hepatocyte intrinsic clearance 14.655 Moderate 0.76
mppb Mouse plasma protein binding (% unbound) 13.490 Moderate 0.76
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 55.719 Moderate 0.76
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 29.610 % Moderate 0.76
rat-kpuu-brain Rat brain Kpuu 0.010 % Moderate 0.76
rh-clint Rat hepatocyte intrinsic clearance 7.413 uL/min/10^6 cells Moderate 0.76
rh-fuinc Rat hepatocyte fraction unbound in incubation 70.340 % Moderate 0.76
rppb Rat plasma protein binding (% unbound) 13.840 % Moderate 0.76
solubility-dd Solubility at pH 7.4 in DMSO 80.910 uM Moderate 0.76

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 1280.61 32.32 404 3467 156211 90468365
Death 130.08 32.32 126 3745 456425 90168151
Pneumonitis 112.77 32.32 49 3822 44121 90580455
Diarrhoea 101.95 32.32 159 3712 939031 89685545
Off label use 99.99 32.32 172 3699 1102080 89522496
Colitis 88.54 32.32 48 3823 69894 90554682
Neutropenia 81.12 32.32 71 3800 224833 90399743
Cytomegalovirus infection 76.08 32.32 32 3839 26570 90598006
Non-small cell lung cancer 69.02 32.32 19 3852 4362 90620214
Progressive multifocal leukoencephalopathy 55.59 32.32 22 3849 15633 90608943
Chronic lymphocytic leukaemia refractory 49.53 32.32 7 3864 44 90624532
Chronic lymphocytic leukaemia recurrent 47.45 32.32 9 3862 390 90624186
Dehydration 46.49 32.32 49 3822 194398 90430178
Lymph node palpable 43.26 32.32 7 3864 118 90624458
Pseudolymphoma 43.21 32.32 9 3862 631 90623945
Pneumonia 42.89 32.32 88 3783 637971 89986605
Hemianopia 42.10 32.32 11 3860 2071 90622505
Immune reconstitution inflammatory syndrome 40.14 32.32 14 3857 7005 90617571
Transaminases increased 40.12 32.32 23 3848 37169 90587407
Respiratory failure 39.83 32.32 36 3835 118382 90506194
B-cell lymphoma recurrent 39.06 32.32 8 3863 516 90624060
Nonspecific reaction 38.84 32.32 11 3860 2798 90621778
Diffuse large B-cell lymphoma refractory 38.77 32.32 10 3861 1790 90622786
Neutropenic infection 38.72 32.32 10 3861 1799 90622777
Blood disorder 38.71 32.32 14 3857 7776 90616800
Disseminated mucormycosis 37.09 32.32 8 3863 663 90623913
Anosognosia 36.38 32.32 11 3860 3511 90621065
Febrile neutropenia 36.23 32.32 39 3832 158310 90466266
Pyrexia 35.17 32.32 83 3788 660402 89964174
Clostridium difficile colitis 32.84 32.32 18 3853 26688 90597888

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 1456.32 26.81 605 5845 143051 42471834
Diarrhoea 208.66 26.81 298 6152 460551 42154334
Pneumonitis 183.25 26.81 100 6350 41618 42573267
Colitis 181.01 26.81 103 6347 46469 42568416
Pneumonia 103.06 26.81 208 6242 421941 42192944
Death 82.06 26.81 203 6247 470982 42143903
Chronic lymphocytic leukaemia recurrent 70.25 26.81 17 6433 651 42614234
Pyrexia 56.35 26.81 158 6292 393884 42221001
Dehydration 53.79 26.81 85 6365 141682 42473203
Lymphocytosis 52.24 26.81 19 6431 3012 42611873
Lung disorder 52.00 26.81 49 6401 47874 42567011
Neutropenia 46.78 26.81 97 6353 199334 42415551
Off label use 42.99 26.81 200 6250 638135 41976750
Febrile neutropenia 40.83 26.81 88 6362 185615 42429270
Pneumocystis jirovecii infection 38.63 26.81 15 6435 2845 42612040
Lymphoma transformation 38.31 26.81 10 6440 522 42614363
Electrolyte imbalance 36.62 26.81 26 6424 17075 42597810
Scopulariopsis infection 32.61 26.81 7 6443 155 42614730
Dermatitis exfoliative 31.39 26.81 17 6433 6930 42607955
Hepatocellular injury 31.15 26.81 27 6423 23651 42591234
Mixed dementia 28.95 26.81 7 6443 267 42614618
Dermatitis exfoliative generalised 28.41 26.81 15 6435 5809 42609076
Cytomegalovirus colitis 27.55 26.81 13 6437 3968 42610917
Atypical pneumonia 27.19 26.81 13 6437 4084 42610801

FDA Adverse Event Reporting System (Geriatric)

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 2325.52 27.28 837 8451 243197 110336814
Colitis 240.76 27.28 133 9155 102190 110477821
Diarrhoea 239.92 27.28 377 8911 1139128 109440883
Pneumonitis 232.49 27.28 118 9170 76413 110503598
Death 198.54 27.28 267 9021 698602 109881409
Pneumonia 134.67 27.28 253 9035 876461 109703550
Dehydration 109.77 27.28 126 9162 279385 110300626
Neutropenia 105.64 27.28 143 9145 374477 110205534
Pyrexia 90.96 27.28 219 9069 898046 109681965
Off label use 90.60 27.28 303 8985 1499882 109080129
Febrile neutropenia 80.37 27.28 115 9173 316652 110263359
Progressive multifocal leukoencephalopathy 68.52 27.28 36 9252 24920 110555091
Electrolyte imbalance 60.29 27.28 38 9250 36990 110543021
Cytomegalovirus infection 55.79 27.28 42 9246 54402 110525609
Pneumocystis jirovecii pneumonia 52.97 27.28 37 9251 42698 110537313
Chronic lymphocytic leukaemia recurrent 52.02 27.28 13 9275 1036 110578975
Chronic lymphocytic leukaemia refractory 51.45 27.28 9 9279 121 110579890
Headache 48.54 27.28 8 9280 882369 109697642
Bronchopulmonary aspergillosis 47.00 27.28 30 9258 29833 110550178
Sepsis 45.63 27.28 91 9197 327255 110252756
Lymphocytosis 45.04 27.28 17 9271 5394 110574617
Pneumocystis jirovecii infection 44.67 27.28 16 9272 4384 110575627
Cytomegalovirus colitis 44.04 27.28 18 9270 7043 110572968
Respiratory tract infection 43.77 27.28 41 9247 71576 110508435
Lymphoma transformation 42.90 27.28 10 9278 594 110579417
Non-small cell lung cancer 42.01 27.28 18 9270 7917 110572094
Blood disorder 38.35 27.28 18 9270 9792 110570219
Herpes zoster 37.70 27.28 46 9242 108333 110471678
Respiratory failure 36.36 27.28 65 9223 215267 110364744
Scopulariopsis infection 35.87 27.28 7 9281 176 110579835
Lymph node palpable 35.28 27.28 7 9281 192 110579819
Hemianopia 35.15 27.28 12 9276 2856 110577155
Tumour lysis syndrome 34.33 27.28 25 9263 30776 110549235
Lung disorder 33.85 27.28 57 9231 179990 110400021
Hepatocellular injury 32.89 27.28 30 9258 50612 110529399
Pain 32.62 27.28 20 9268 954935 109625076
Mixed dementia 32.58 27.28 7 9281 286 110579725
Atypical pneumonia 32.52 27.28 15 9273 7847 110572164
Renal failure 31.56 27.28 63 9225 226511 110353500
Pseudolymphoma 31.28 27.28 9 9279 1226 110578785
Transaminases increased 30.76 27.28 32 9256 63358 110516653
Nonspecific reaction 30.54 27.28 11 9277 3063 110576948
Blood lactate dehydrogenase increased 30.25 27.28 27 9261 44307 110535704
Dermatitis exfoliative 30.10 27.28 16 9272 11331 110568680
Diffuse large B-cell lymphoma refractory 28.77 27.28 10 9278 2511 110577500
Anosognosia 27.52 27.28 11 9277 4063 110575948

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EM01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Phosphatidylinositol-3-kinase (Pi3K) inhibitors
FDA MoA N0000175082 Kinase Inhibitors
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000190114 Cytochrome P450 3A Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50914 EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor
CHEBI has role CHEBI:68495 apoptosis inducer
CHEBI has role CHEBI:233423 antifibrotic agent

Related Drugs by ATC class:

L01EM Phosphatidylinositol-3-kinase (Pi3K) inhibitors 4 drugs
alpelisibcopanlisibduvelisibinavolisib

Drug Use | Suggest Off label Use Form| |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




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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 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)

None

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 3-kinase catalytic subunit type 3 Kinase IC50 5.36 CHEMBL
DNA-dependent protein kinase catalytic subunit Kinase IC50 5.17 CHEMBL
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform Kinase IC50 6.25 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 alpha isoform Kinase IC50 6.09 SCIENTIFIC LITERATURE
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Kinase IC50 5.88 CHEMBL

External reference:

IDSource
D10560 KEGG_DRUG
4033559 VUID
N0000190926 NUI
4033559 VANDF
40L PDB_CHEM_ID
CHEMBL2216870 ChEMBL_ID
C552946 MESH_SUPPLEMENTAL_RECORD_UI
6741 IUPHAR_LIGAND_ID
DB09054 DRUGBANK_ID
1544460 RXNORM
226727 MMSL
30429 MMSL
d08273 MMSL
015626 NDDF
709283009 SNOMEDCT_US
710278000 SNOMEDCT_US
C2698692 UMLSCUI
CHEBI:82701 CHEBI
9624 INN_ID
11625818 PUBCHEM_CID
YG57I8T5M0 UNII
YG57I8T5M0 INXIGHT DRUGS

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