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

Stem definition	Drug id	CAS RN
phosphatidylinositol 3-kinase inhibitors, antineoplastics	4878	870281-82-6

Description:

Molecule	Description
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: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

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: ONP

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

Drug dosage:

Dose	Unit	Route
0.30	g	O

ADMET properties:

None

Approvals:

Date	Agency	Company	Orphan
July 25, 2014	EMA
July 23, 2014	FDA	GILEAD SCIENCES INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Disease progression	1165.24	31.11	380	3236	122378	63363028
Death	108.26	31.11	119	3497	374262	63111144
Pneumonitis	106.70	31.11	48	3568	35174	63450232
Off label use	97.31	31.11	152	3464	674310	62811096
Diarrhoea	94.69	31.11	155	3461	715211	62770195
Colitis	83.56	31.11	45	3571	48483	63436923
Neutropenia	74.95	31.11	69	3547	174936	63310470
Cytomegalovirus infection	74.57	31.11	32	3584	20920	63464486
Non-small cell lung cancer	67.33	31.11	19	3597	3576	63481830
Chronic lymphocytic leukaemia recurrent	49.29	31.11	9	3607	235	63485171
Chronic lymphocytic leukaemia refractory	47.52	31.11	7	3609	44	63485362
Pneumonia	45.80	31.11	88	3528	456679	63028727
Lymph node palpable	42.08	31.11	7	3609	104	63485302
Pseudolymphoma	40.78	31.11	9	3607	620	63484786
Progressive multifocal leukoencephalopathy	40.26	31.11	18	3598	12953	63472453
Lung disorder	39.86	31.11	31	3585	62230	63423176
Dehydration	39.58	31.11	49	3567	173305	63312101
B-cell lymphoma recurrent	38.67	31.11	8	3608	405	63485001
Neutropenic infection	38.65	31.11	10	3606	1357	63484049
Nonspecific reaction	37.92	31.11	11	3605	2281	63483125
Blood disorder	36.70	31.11	14	3602	6757	63478649
Pyrexia	35.81	31.11	81	3535	470397	63015009
Respiratory failure	35.64	31.11	36	3580	101822	63383584
B-cell lymphoma refractory	35.42	31.11	6	3610	100	63485306
Transaminases increased	32.59	31.11	21	3595	31346	63454060
Febrile neutropenia	31.15	31.11	36	3580	118413	63366993

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Disease progression	1460.87	27.92	581	5471	107496	34843383
Diarrhoea	205.92	27.92	291	5761	389621	34561258
Pneumonitis	190.22	27.92	100	5952	33778	34917101
Colitis	174.59	27.92	98	5954	37652	34913227
Pneumonia	85.68	27.92	191	5861	362436	34588443
Death	84.54	27.92	201	5851	397848	34553031
Chronic lymphocytic leukaemia recurrent	76.23	27.92	17	6035	393	34950486
Off label use	62.62	27.92	186	5866	419338	34531541
Pyrexia	58.76	27.92	157	5895	332856	34618023
Lymphocytosis	52.75	27.92	19	6033	2558	34948321
Dehydration	50.80	27.92	85	5967	129884	34820995
Neutropenia	49.03	27.92	93	5959	156685	34794194
Lung disorder	45.80	27.92	42	6010	34654	34916225
Pneumocystis jirovecii infection	43.69	27.92	15	6037	1755	34949124
Lymphoma transformation	43.46	27.92	10	6042	267	34950612
Electrolyte imbalance	37.48	27.92	26	6026	14386	34936493
Febrile neutropenia	33.04	27.92	73	5979	136776	34814103
Cytomegalovirus colitis	30.33	27.92	13	6039	2771	34948108
Respiratory tract infection	30.25	27.92	26	6026	19686	34931193
Dermatitis exfoliative	29.97	27.92	17	6035	6622	34944257
Hepatocellular injury	29.51	27.92	27	6025	22184	34928695

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Disease progression	2192.04	25.88	796	7858	183566	79552168
Colitis	228.06	25.88	125	8529	73182	79662552
Pneumonitis	226.62	25.88	117	8537	60743	79674991
Diarrhoea	225.40	25.88	366	8288	880123	78855611
Death	178.71	25.88	260	8394	566254	79169480
Pneumonia	118.55	25.88	236	8418	660010	79075724
Off label use	104.64	25.88	272	8382	906943	78828791
Neutropenia	97.47	25.88	137	8517	287573	79448161
Dehydration	95.91	25.88	126	8528	248061	79487673
Pyrexia	91.23	25.88	216	8438	678493	79057241
Febrile neutropenia	59.62	25.88	97	8557	230902	79504832
Electrolyte imbalance	57.69	25.88	38	8616	30843	79704891
Cytomegalovirus infection	55.34	25.88	42	8612	42602	79693132
Chronic lymphocytic leukaemia recurrent	54.94	25.88	13	8641	635	79735099
Progressive multifocal leukoencephalopathy	52.80	25.88	31	8623	20569	79715165
Chronic lymphocytic leukaemia refractory	49.42	25.88	9	8645	117	79735617
Pneumocystis jirovecii pneumonia	48.90	25.88	35	8619	32473	79703261
Respiratory tract infection	48.36	25.88	41	8613	48648	79687086
Pneumocystis jirovecii infection	47.22	25.88	16	8638	2878	79732856
Cytomegalovirus colitis	46.73	25.88	18	8636	4667	79731067
Lymphoma transformation	46.36	25.88	10	8644	320	79735414
Lung disorder	46.03	25.88	50	8604	80507	79655227
Headache	45.72	25.88	8	8646	653764	79081970
Lymphocytosis	43.16	25.88	17	8637	4676	79731058
Non-small cell lung cancer	41.41	25.88	18	8636	6342	79729392
Sepsis	39.52	25.88	89	8565	269339	79466395
Lymph node palpable	34.35	25.88	7	8647	169	79735565
Tumour lysis syndrome	34.23	25.88	25	8629	23914	79711820
Mixed dementia	30.84	25.88	7	8647	284	79735450
Nonspecific reaction	29.87	25.88	11	8643	2521	79733213
Pain	29.76	25.88	20	8634	703782	79031952
Pseudolymphoma	29.22	25.88	9	8645	1196	79734538
Respiratory failure	29.03	25.88	62	8592	180849	79554885
Pain in extremity	28.90	25.88	3	8651	364535	79371199
Blood disorder	28.15	25.88	15	8639	8258	79727476
Dermatitis exfoliative	26.97	25.88	16	8638	10813	79724921
Hypogammaglobulinaemia	26.80	25.88	17	8637	12934	79722800
Lymphadenitis viral	26.67	25.88	5	8649	77	79735657
Neutropenic infection	26.64	25.88	10	8644	2417	79733317
Borrelia infection	26.26	25.88	6	8648	251	79735483
Hepatocellular injury	26.24	25.88	29	8625	47564	79688170
Transaminases increased	25.92	25.88	30	8624	51713	79684021

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
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 agents
CHEBI has role	CHEBI:50914	PI(3)K inhibitor
CHEBI has role	CHEBI:68495	Type I cell-death inducers

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

Disease	Relation	SNOMED_ID
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 level	Dissociation constant	Type (acidic/basic)
pKa1	10.29	acidic
pKa2	4.22	Basic
pKa3	2.56	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
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)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform	Kinase	O00329	PK3CD_HUMAN	INHIBITOR	IC50	8.60	SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
DNA-dependent protein kinase catalytic subunit	Kinase	P78527	PRKDC_HUMAN		IC50	5.17	CHEMBL
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	Kinase	P42338	PK3CB_HUMAN		IC50	6.25	SCIENTIFIC LITERATURE
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Kinase	P42336	PK3CA_HUMAN		IC50	6.09	SCIENTIFIC LITERATURE
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	Kinase	P48736	PK3CG_HUMAN		IC50	7.05	SCIENTIFIC LITERATURE
Phosphatidylinositol 3-kinase catalytic subunit type 3	Kinase	Q8NEB9	PK3C3_HUMAN		IC50	5.36	CHEMBL
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	Kinase		PK3CG_MOUSE		IC50	5.88	CHEMBL

External reference:

ID	Source
D10560	KEGG_DRUG
4033559	VUID
N0000190926	NUI
4033559	VANDF
CHEBI:82701	CHEBI
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
9624	INN_ID
11625818	PUBCHEM_CID
YG57I8T5M0	UNII

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Zydelig	HUMAN PRESCRIPTION DRUG LABEL	1	61958-1701	TABLET, FILM COATED	100 mg	ORAL	NDA	33 sections
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
Zydelig	HUMAN PRESCRIPTION DRUG LABEL	1	61958-1702	TABLET, FILM COATED	150 mg	ORAL	NDA	33 sections