Details of the Drug

General Information of Drug (ID: DMHZCPO)

Drug Name

Ibrutinib

Synonyms

PCI-32765; Ibrutinib (BTK inhibitor)

Indication

Disease Entry	ICD 11	Status	REF
Mantle cell lymphoma	2A85.5	Approved	[1]
Small lymphocytic lymphoma	2A82.0	Approved	[2]
Waldenstrom macroglobulinemia	2A85.4	Approved	[2]
B-cell non-hodgkin lymphoma	2B33.5	Phase 3	[3]
Diffuse large B-cell lymphoma	2A81	Phase 3	[3]
Follicular lymphoma	2A80	Phase 3	[3]
Non-hodgkin lymphoma	2B33.5	Phase 3	[3]
Pancreatic cancer	2C10	Phase 3	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[4]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

440.5

Logarithm of the Partition Coefficient (xlogp)

3.6

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Clearance: The drug present in the plasma can be removed from the body at the rate of 16.4 mL/min/kg [5]
Half-life: The concentration or amount of drug in body reduced by one-half in 5 hours [5]
Unbound Fraction: The unbound fraction of drug in plasma is 0.03% [5]
Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 9.75 L/kg [5]

Chemical Identifiers

Formula: C25H24N6O2
IUPAC Name: 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one
Canonical SMILES: C=CC(=O)N1CCC[C@H](C1)N2C3=NC=NC(=C3C(=N2)C4=CC=C(C=C4)OC5=CC=CC=C5)N
InChI: InChI=1S/C25H24N6O2/c1-2-21(32)30-14-6-7-18(15-30)31-25-22(24(26)27-16-28-25)23(29-31)17-10-12-20(13-11-17)33-19-8-4-3-5-9-19/h2-5,8-13,16,18H,1,6-7,14-15H2,(H2,26,27,28)/t18-/m1/s1
InChIKey: XYFPWWZEPKGCCK-GOSISDBHSA-N

Cross-matching ID

PubChem CID: 24821094
ChEBI ID: CHEBI:76612
CAS Number: 936563-96-1
DrugBank ID: DB09053
TTD ID: D09KTS
VARIDT ID: DR01270
INTEDE ID: DR0843
ACDINA ID: D01146

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Tyrosine-protein kinase BTK (ATK)	TTGM6VW	BTK_HUMAN	Inhibitor	[6]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[8]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[8]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[8]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2)	OTGVC9MY	PLCG2_HUMAN	Post-Translational Modifications	[9]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Protein Interaction/Cellular Processes	[10]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Protein Interaction/Cellular Processes	[11]
Baculoviral IAP repeat-containing protein 3 (BIRC3)	OT3E95KB	BIRC3_HUMAN	Gene/Protein Processing	[9]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Gene/Protein Processing	[9]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Gene/Protein Processing	[9]
CREB-binding protein (CREBBP)	OTPA4QGM	CBP_HUMAN	Drug Response	[9]
Hemoglobin subunit beta (HBB)	OT514IKQ	HBB_HUMAN	Protein Interaction/Cellular Processes	[11]
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB)	OT9RDS3H	IKKB_HUMAN	Gene/Protein Processing	[12]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Gene/Protein Processing	[9]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Mantle cell lymphoma

ICD Disease Classification

2A85.5

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Tyrosine-protein kinase BTK (ATK)	DTT	BTK	3.54E-01	0.24	0.56
P-glycoprotein 1 (ABCB1)	DTP	P-GP	7.45E-02	-1.49E-01	-3.47E-01
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	1.34E-01	-2.79E-01	-7.05E-01
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	1.61E-03	-6.79E-01	-2.18E+00
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	9.81E-01	2.72E-01	6.95E-01

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Ibrutinib

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Acalabrutinib	DM7GCVW	Major	Increased risk of bleeding by the combination of Ibrutinib and Acalabrutinib.	Mature B-cell lymphoma [2A85]	[13]
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Coadministration of a Drug Treating the Disease Different from Ibrutinib (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Ibrutinib caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[14]
Arn-509	DMT81LZ	Major	Increased metabolism of Ibrutinib caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[15]
Gilteritinib	DMTI0ZO	Moderate	Decreased clearance of Ibrutinib due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[15]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Ibrutinib caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[14]
Talazoparib	DM1KS78	Moderate	Decreased clearance of Ibrutinib due to the transporter inhibition by Talazoparib.	Breast cancer [2C60-2C6Y]	[16]
Tucatinib	DMBESUA	Major	Decreased metabolism of Ibrutinib caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[17]
Lumacaftor	DMCLWDJ	Major	Increased metabolism of Ibrutinib caused by Lumacaftor mediated induction of CYP450 enzyme.	Cystic fibrosis [CA25]	[15]
Vortioxetine	DM6F1PU	Moderate	Increased risk of bleeding by the combination of Ibrutinib and Vortioxetine.	Depression [6A70-6A7Z]	[18]
Tazemetostat	DMWP1BH	Major	Increased risk of bleeding by the combination of Ibrutinib and Tazemetostat.	Follicular lymphoma [2A80]	[19]
Ripretinib	DM958QB	Moderate	Decreased clearance of Ibrutinib due to the transporter inhibition by Ripretinib.	Gastrointestinal stromal tumour [2B5B]	[17]
Avapritinib	DMK2GZX	Major	Increased risk of bleeding by the combination of Ibrutinib and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[15]
Cobicistat	DM6L4H2	Major	Decreased metabolism of Ibrutinib caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[17]
Epanova	DMHEAGL	Major	Increased risk of bleeding by the combination of Ibrutinib and Epanova.	Hyper-lipoproteinaemia [5C80]	[20]
Ceritinib	DMB920Z	Major	Decreased metabolism of Ibrutinib caused by Ceritinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[17]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Ibrutinib caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[14]
Idelalisib	DM602WT	Major	Decreased metabolism of Ibrutinib caused by Idelalisib mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[17]
GDC-0199	DMH0QKA	Major	Decreased clearance of Ibrutinib due to the transporter inhibition by GDC-0199.	Mature B-cell leukaemia [2A82]	[17]
Arry-162	DM1P6FR	Major	Increased risk of bleeding by the combination of Ibrutinib and Arry-162.	Melanoma [2C30]	[19]
LGX818	DMNQXV8	Major	Increased risk of bleeding by the combination of Ibrutinib and LGX818.	Melanoma [2C30]	[19]
Ubrogepant	DM749I3	Moderate	Decreased clearance of Ibrutinib due to the transporter inhibition by Ubrogepant.	Migraine [8A80]	[21]
Rimegepant	DMHOAUG	Moderate	Decreased clearance of Ibrutinib due to the transporter inhibition by Rimegepant.	Migraine [8A80]	[22]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Ibrutinib and Siponimod.	Multiple sclerosis [8A40]	[17]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Ibrutinib and Ocrelizumab.	Multiple sclerosis [8A40]	[23]
Fedratinib	DM4ZBK6	Major	Increased risk of bleeding by the combination of Ibrutinib and Fedratinib.	Myeloproliferative neoplasm [2A20]	[14]
Lefamulin	DME6G97	Moderate	Decreased clearance of Ibrutinib due to the transporter inhibition by Lefamulin.	Pneumonia [CA40]	[24]
Relugolix	DMK7IWL	Moderate	Decreased clearance of Ibrutinib due to the transporter inhibition by Relugolix.	Prostate cancer [2C82]	[15]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Ibrutinib when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[25]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of Ibrutinib caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[14]
Larotrectinib	DM26CQR	Moderate	Decreased clearance of Ibrutinib due to the transporter inhibition by Larotrectinib.	Solid tumour/cancer [2A00-2F9Z]	[14]
Lusutrombopag	DMH6IKO	Moderate	Decreased clearance of Ibrutinib due to the transporter inhibition by Lusutrombopag.	Thrombocytopenia [3B64]	[26]
Elagolix	DMB2C0E	Moderate	Increased metabolism of Ibrutinib caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[14]
Betrixaban	DM2C4RF	Major	Increased risk of bleeding by the combination of Ibrutinib and Betrixaban.	Venous thromboembolism [BD72]	[19]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Carmellose sodium	E00625	Not Available	Disintegrant
Ferrosoferric oxide	E00231	14789	Colorant
Gelatin	E00630	Not Available	Other agent
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Colcothar yellow	E00436	518696	Colorant
Haematite red	E00236	14833	Colorant
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
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⏷ Show the Full List of 15 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Ibrutinib 280mg tablet	280mg	Tablet	Oral
Ibrutinib 140mg tablet	140mg	Tablet	Oral
Ibrutinib 560mg tablet	560mg	Tablet	Oral
Ibrutinib 420mg tablet	420mg	Tablet	Oral
Ibrutinib 70mg capsule	70mg	Capsule	Oral
Ibrutinib 140mg capsule	140mg	Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6912).
2	Ibrutinib FDA Label
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4	Ibrutinib for the Treatment of COVID-19 in Patients Requiring Hospitalization
5	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1948).
7	P-Glycoprotein (MDR1/ABCB1) Restricts Brain Penetration of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib, While Cytochrome P450-3A (CYP3A) Limits Its Oral Bioavailability. Mol Pharm. 2018 Nov 5;15(11):5124-5134.
8	Absorption, metabolism, and excretion of oral 14C radiolabeled ibrutinib: an open-label, phase I, single-dose study in healthy men. Drug Metab Dispos. 2015 Feb;43(2):289-97.
9	Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib. Blood. 2015 Sep 24;126(13):1565-74.
10	Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
11	Label-Free Bottom-Up Proteomic Workflow for Simultaneously Assessing the Target Specificity of Covalent Drug Candidates and Their Off-Target Reactivity to Selected Proteins. Chem Res Toxicol. 2016 Jan 19;29(1):109-16. doi: 10.1021/acs.chemrestox.5b00460. Epub 2015 Dec 29.
12	Blockade of oncogenic IB kinase activity in diffuse large B-cell lymphoma by bromodomain and extraterminal domain protein inhibitors. Proc Natl Acad Sci U S A. 2014 Aug 5;111(31):11365-70. doi: 10.1073/pnas.1411701111. Epub 2014 Jul 21.
13	Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
14	Product Information. Imbruvica (ibrutinib). Pharmacyclics Inc, Sunnyvale, CA.
15	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
16	Product Information. Talzenna (talazoparib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
17	Cerner Multum, Inc. "Australian Product Information.".
18	Alderman CP, Moritz CK, Ben-Tovim DI "Abnormal platelet aggregation associated with fluoxetine therapy." Ann Pharmacother 26 (1992): 1517-9. [PMID: 1482806]
19	Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
20	Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
21	Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
22	Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
23	Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
24	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
25	CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]
26	EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".