Idelalisib

Identification

Name

Idelalisib

Accession Number

DB09054

Description

Idelalisib is a phosphoinositide 3-kinase inhibitor indicated in the treatment of chronic lymphocytic leukemia (CLL), relapsed follicular B-cell non-Hodgkin lymphoma (FL), and relapsed small lymphocytic lymphoma (SLL). For the treatment of relapsed CLL, it is currently indicated as a second-line agent in combination with rituximab in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities, while in the treatment of FL and SLL it is intended to be used in patients who have received at least two prior systemic therapies. More specifically, idelalisib targets P110δ, the delta isoform of the enzyme phosphatidylinositol-4,5-bisphosphate 3-kinase, also known as PI-3K. The PI-3Ks are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. In contrast to the other class IA PI3Ks p110α and p110β, p110δ is principally expressed in leukocytes (white blood cells) and is important for the function of T cells, B cell, mast cells and neutrophils. By inhibiting this enzyme, idelalisib induces apoptosis of malignant cells and inhibits several cell signaling pathways, including B-cell receptor (BCR) signaling and C-X-C chemokine receptors type 5 and type 4 signalling, which are involved in trafficking and homing of B-cells to the lymph nodes and bone marrow. Treatment of lymphoma cells with idelalisib has been shown to result in inhibition of chemotaxis and adhesion, and reduced cell viability.

Type

Small Molecule

Groups

Approved

Structure

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Idelalisib (DB09054)

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Weight

Average: 415.432
Monoisotopic: 415.155686391

Chemical Formula

C₂₂H₁₈FN₇O

Synonyms

• 5-Fluoro-3-phenyl-2-((S)-1-(9H-purin-6-ylamino)-propyl)-3H-quinazolin-4-one
• 5-fluoro-3-phenyl-2-[(1S)-1-(3H-purin-6-ylamino)propyl]quinazolin-4(3H)-one
• Idelalisib

External IDs

• CAL 101
• CAL-101
• CAL101
• GS 1101
• GS-1101
• GS1101

Pharmacology

Indication

Idelalisib is indicated in the treatment of chronic lymphocytic leukemia (CLL), relapsed follicular B-cell non-Hodgkin lymphoma (FL), and relapsed small lymphocytic lymphoma (SLL). For the treatment of relapsed CLL, it is currently indicated as a second-line agent in combination with rituximab in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities, while in the treatment of FL and SLL it is intended to be used in patients who have received at least two prior systemic therapies.

Associated Conditions

• Relapsed Chronic Lymphocytic Leukemia
• Relapsed Small Lymphocytic Lymphoma
• Relapsed follicular B-cell non-Hodgkin lymphoma

Contraindications & Blackbox Warnings

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Pharmacodynamics

Not Available

Mechanism of action

Idelalisib specifically inhibits P110δ, the delta isoform of the enzyme phosphatidylinositol-4,5-bisphosphate 3-kinase, also known as PI-3K. The PI-3Ks are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. In contrast to the other class IA PI3Ks p110α and p110β, p110δ is principally expressed in leukocytes (white blood cells) and is important for the function of T cells, B cell, mast cells and neutrophils. By inhibiting this enzyme, idelalisib induces apoptosis of malignant cells and inhibits several cell signaling pathways, including B-cell receptor (BCR) signaling and C-X-C chemokine receptors type 5 and type 4 signalling, which are involved in trafficking and homing of B-cells to the lymph nodes and bone marrow. Treatment of lymphoma cells with idelalisib has been shown to result in inhibition of chemotaxis and adhesion, and reduced cell viability.

Target	Actions	Organism
APhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform	inhibitor	Humans

Absorption

Following oral administration, the median Tmax was observed at 1.5 hours.

Volume of distribution

23 L

Protein binding

Idelalisib is greater than 84% bound to human plasma proteins with no concentration dependence.

Metabolism

Idelalisib is metabolized by aldehyde oxidase and CYP3A to its major metabolite GS-563117, which is inactive against P110δ. Idelalisib is also metabolized to a minor extent by UGT1A4.

Hover over products below to view reaction partners

• Idelalisib
  • GS-563117

Route of elimination

Following a single dose of 150 mg of [14C] idelalisib, 78% and 14% of the radioactivity was excreted in feces and urine, respectively. GS-563117, idelalisib's major metabolite, accounted for 49% of the radioactivity in the urine and 44% in the feces.

Half-life

The terminal elimination half-life is 8.2 hours.

Clearance

14.9 L/hr

Adverse Effects

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Toxicity

Not Available

Affected organisms

• Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Abametapir	The serum concentration of Idelalisib can be increased when it is combined with Abametapir.
Abatacept	The metabolism of Idelalisib can be increased when combined with Abatacept.
Abemaciclib	The metabolism of Idelalisib can be decreased when combined with Abemaciclib.
Abiraterone	The metabolism of Idelalisib can be decreased when combined with Abiraterone.
Acalabrutinib	The metabolism of Idelalisib can be decreased when combined with Acalabrutinib.
Acenocoumarol	The serum concentration of Acenocoumarol can be increased when it is combined with Idelalisib.
Acetaminophen	The metabolism of Idelalisib can be increased when combined with Acetaminophen.
Acetazolamide	The metabolism of Idelalisib can be decreased when combined with Acetazolamide.
Adalimumab	The metabolism of Idelalisib can be increased when combined with Adalimumab.
Adenovirus type 7 vaccine live	The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Idelalisib.

Additional Data Available

Extended Description
Extended Description
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Severity
Severity
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Evidence Level
Evidence Level
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Action
Action
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Food Interactions

• Avoid grapefruit products. Grapefruit inhibits the CYP3A metabolism of idelalisib, which may increase its serum concentration.
• Avoid St. John's Wort. This herb induces the CYP3A metabolism of idelalisib and may reduce its serum concentration.
• Take with or without food. Taking idelalisib with a high-fat meal may increase the AUC by 1.4 fold.

Products

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
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Zydelig	Tablet, film coated	150 mg/1	Oral	Gilead Sciences, Inc.	2014-07-23	Not applicable
Zydelig	Tablet, film coated	100 mg	Oral	Gilead Sciences Ireland Uc	2014-09-18	Not applicable
Zydelig	Tablet	150 mg	Oral	Gilead Sciences	2015-04-21	Not applicable
Zydelig	Tablet, film coated	100 mg/1	Oral	Gilead Sciences, Inc.	2014-07-23	Not applicable
Zydelig	Tablet	100 mg	Oral	Gilead Sciences	2015-04-21	Not applicable
Zydelig	Tablet, film coated	150 mg	Oral	Gilead Sciences Ireland Uc	2014-09-18	Not applicable

Additional Data Available

Application Number
Application Number
Available for Purchase
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
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Product Code
Product Code
Available for Purchase
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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Categories

ATC Codes

L01XX47 — Idelalisib

• L01XX — Other antineoplastic agents
• L01X — OTHER ANTINEOPLASTIC AGENTS
• L01 — ANTINEOPLASTIC AGENTS
• L — ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Drug Categories

• Antineoplastic Agents
• Antineoplastic and Immunomodulating Agents
• BCRP/ABCG2 Substrates
• Cancer immunotherapy
• Class Ia Phosphatidylinositol 3-Kinase, antagonists & inhibitors
• Cytochrome P-450 CYP2B6 Inducers
• Cytochrome P-450 CYP2B6 Inducers (strength unknown)
• Cytochrome P-450 CYP2C19 Inhibitors
• Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
• Cytochrome P-450 CYP2C8 Inhibitors
• Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
• Cytochrome P-450 CYP2C8 Inhibitors (weak)
• Cytochrome P-450 CYP3A Inducers
• Cytochrome P-450 CYP3A Inhibitors
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Inducers
• Cytochrome P-450 CYP3A4 Inducers (strength unknown)
• Cytochrome P-450 CYP3A4 Inhibitors
• Cytochrome P-450 CYP3A4 Inhibitors (strong)
• Cytochrome P-450 CYP3A4 Substrates
• Cytochrome P-450 CYP3A4 Substrates (strength unknown)
• Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
• Cytochrome P-450 CYP3A5 Inhibitors
• Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)
• Cytochrome P-450 CYP3A5 Substrates
• Cytochrome P-450 CYP3A5 Substrates with a Narrow Therapeutic Index
• Cytochrome P-450 CYP3A7 Inhibitors
• Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)
• Cytochrome P-450 CYP3A7 Substrates
• Cytochrome P-450 CYP3A7 Substrates with a Narrow Therapeutic Index
• Cytochrome P-450 Enzyme Inducers
• Cytochrome P-450 Enzyme Inhibitors
• Cytochrome P-450 Substrates
• Enzyme Inhibitors
• Hepatotoxic Agents
• Heterocyclic Compounds, Fused-Ring
• Immunosuppressive Agents
• Immunotherapy
• Kinase Inhibitor
• Narrow Therapeutic Index Drugs
• OATP1B1/SLCO1B1 Inhibitors
• OATP1B3 inhibitors
• P-glycoprotein inhibitors
• P-glycoprotein substrates
• P-glycoprotein substrates with a Narrow Therapeutic Index
• Quinazolines
• UGT1A4 Inhibitors
• UGT1A4 substrates

Chemical TaxonomyProvided by Classyfire

Description

This compound belongs to the class of organic compounds known as 6-alkylaminopurines. These are compounds that contain an alkylamine group attached at the 6-position of a purine. Purine is a bicyclic aromatic compound made up of a pyrimidine ring fused to an imidazole ring.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Imidazopyrimidines

Sub Class

Purines and purine derivatives

Direct Parent

6-alkylaminopurines

Alternative Parents

Quinazolines / Secondary alkylarylamines / Pyrimidones / Aminopyrimidines and derivatives / Aryl fluorides / Benzene and substituted derivatives / Imidolactams / Vinylogous halides / Heteroaromatic compounds / Imidazoles / Lactams / Azacyclic compounds / Hydrocarbon derivatives / Organic oxides / Organofluorides / Organooxygen compounds / Organopnictogen compounds

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Substituents

6-alkylaminopurine / Amine / Aminopyrimidine / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Azole / Benzenoid / Diazanaphthalene / Heteroaromatic compound / Hydrocarbon derivative / Imidazole / Imidolactam / Lactam / Monocyclic benzene moiety / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organofluoride / Organohalogen compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Pyrimidine / Pyrimidone / Quinazoline / Secondary aliphatic/aromatic amine / Secondary amine / Vinylogous halide

show 20 more

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

organofluorine compound, secondary amino compound, aromatic amine, purines, quinazolines (CHEBI:82701)

Chemical Identifiers

UNII

YG57I8T5M0

CAS number

870281-82-6

InChI Key

IFSDAJWBUCMOAH-HNNXBMFYSA-N

InChI

InChI=1S/C22H18FN7O/c1-2-15(28-20-18-19(25-11-24-18)26-12-27-20)21-29-16-10-6-9-14(23)17(16)22(31)30(21)13-7-4-3-5-8-13/h3-12,15H,2H2,1H3,(H2,24,25,26,27,28)/t15-/m0/s1

IUPAC Name

5-fluoro-3-phenyl-2-[(1S)-1-[(9H-purin-6-yl)amino]propyl]-3,4-dihydroquinazolin-4-one

SMILES

[H][C@@](CC)(NC1=NC=NC2=C1N=CN2)C1=NC2=CC=CC(F)=C2C(=O)N1C1=CC=CC=C1

References

General References

1. Jin F, Robeson M, Zhou H, Moyer C, Wilbert S, Murray B, Ramanathan S: Clinical drug interaction profile of idelalisib in healthy subjects. J Clin Pharmacol. 2015 Aug;55(8):909-19. doi: 10.1002/jcph.495. Epub 2015 May 6. [PubMed:25760671]
2. Fiorcari S, Brown WS, McIntyre BW, Estrov Z, Maffei R, O'Brien S, Sivina M, Hoellenriegel J, Wierda WG, Keating MJ, Ding W, Kay NE, Lannutti BJ, Marasca R, Burger JA: The PI3-kinase delta inhibitor idelalisib (GS-1101) targets integrin-mediated adhesion of chronic lymphocytic leukemia (CLL) cell to endothelial and marrow stromal cells. PLoS One. 2013 Dec 23;8(12):e83830. doi: 10.1371/journal.pone.0083830. eCollection 2013. [PubMed:24376763]
3. Flinn IW, Kahl BS, Leonard JP, Furman RR, Brown JR, Byrd JC, Wagner-Johnston ND, Coutre SE, Benson DM, Peterman S, Cho Y, Webb HK, Johnson DM, Yu AS, Ulrich RG, Godfrey WR, Miller LL, Spurgeon SE: Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-delta, as therapy for previously treated indolent non-Hodgkin lymphoma. Blood. 2014 May 29;123(22):3406-13. doi: 10.1182/blood-2013-11-538546. Epub 2014 Mar 10. [PubMed:24615776]
4. Brown JR, Byrd JC, Coutre SE, Benson DM, Flinn IW, Wagner-Johnston ND, Spurgeon SE, Kahl BS, Bello C, Webb HK, Johnson DM, Peterman S, Li D, Jahn TM, Lannutti BJ, Ulrich RG, Yu AS, Miller LL, Furman RR: Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110delta, for relapsed/refractory chronic lymphocytic leukemia. Blood. 2014 May 29;123(22):3390-7. doi: 10.1182/blood-2013-11-535047. Epub 2014 Mar 10. [PubMed:24615777]
5. FDA Approval: Idelalisib Monotherapy for the Treatment of Patients with Follicular Lymphoma and Small Lymphocytic Lymphoma [File]

External Links

KEGG Drug

D10560

PubChem Compound

11625818

PubChem Substance

310264996

ChemSpider

9800565

BindingDB

150175

RxNav

1544460

ChEBI

82701

ChEMBL

CHEMBL2216870

ZINC

ZINC000013986658

PDBe Ligand

40L

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Idelalisib

AHFS Codes

• 10:00.00 — Antineoplastic Agents

PDB Entries

4xe0

FDA label

Download (496 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Terminated	Treatment	Lymphoid Malignancies	1
3	Active Not Recruiting	Treatment	Chronic Lymphocytic Leukaemia (CLL)	1
3	Completed	Treatment	Chronic Lymphocytic Leukaemia (CLL)	2
3	Not Yet Recruiting	Treatment	Chronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma	1
3	Recruiting	Treatment	Follicular Lymphoma (FL)	1
3	Terminated	Treatment	Chronic Lymphocytic Leukaemia (CLL)	4
3	Terminated	Treatment	Indolent Non-Hodgkin's Lymphomas	2
2	Active Not Recruiting	Treatment	Chronic Lymphocytic Leucemia	1
2	Active Not Recruiting	Treatment	Chronic Lymphocytic Leukaemia (CLL)	1
2	Active Not Recruiting	Treatment	Chronic Lymphocytic Leukaemia (CLL) / Leukemia, Lymphocytic, Chronic, B-Cell / Small Lymphocytic Lymphoma	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Tablet	Oral	100 mg
Tablet	Oral	150 mg
Tablet, film coated	Oral	100 mg
Tablet, film coated	Oral	100 mg/1
Tablet, film coated	Oral	150 mg
Tablet, film coated	Oral	150 mg/1

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
Unlock Additional Data
US6949535	No	2005-09-27	2021-04-24
US6800620	No	2004-10-05	2021-04-24
US8980901	No	2015-03-17	2025-05-12
US9149477	No	2015-10-06	2025-05-12
US8138195	No	2012-03-20	2021-04-24
USRE44599	No	2013-11-12	2025-07-21
US8865730	No	2014-10-21	2033-03-05
US8637533	No	2014-01-28	2021-04-24
USRE44638	No	2013-12-10	2025-08-05
US8492389	No	2013-07-23	2021-04-24
US9469643	No	2016-10-18	2033-09-02
US9492449	No	2016-11-15	2030-03-11
US10730879	No	2013-03-05	2033-03-05

Additional Data Available

Filed On
Filed On
Available for Purchase
The date on which a patent was filed with the relevant government.
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Properties

State

Solid

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.0255 mg/mL	ALOGPS
logP	3.03	ALOGPS
logP	3.36	ChemAxon
logS	-4.2	ALOGPS
pKa (Strongest Acidic)	9.86	ChemAxon
pKa (Strongest Basic)	4.27	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	6	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	99.16 Å2	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	116.83 m3·mol-1	ChemAxon
Polarizability	41.41 Å3	ChemAxon
Number of Rings	5	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

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Drug created on May 08, 2015 13:47 / Updated on January 16, 2021 14:46