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]
⏷ Show the Full List of Indication(s)
Affected Organisms
Humans and other mammals
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) 5
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 6
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
CHEMBL1873475
CAS Number
936563-96-1
UNII
1X70OSD4VX
DrugBank ID
DB09053
TTD ID
D09KTS
VARIDT ID
DR01270
INTEDE ID
DR0843
ACDINA ID
D01146
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

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]

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

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]

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]
Albumin (ALB) OTVMM513 ALBU_HUMAN Protein Interaction/Cellular Processes [10]
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]
Mitogen-activated protein kinase kinase kinase 14 (MAP3K14) OTT3DOOL M3K14_HUMAN Drug Response [9]
PR domain zinc finger protein 1 (PRDM1) OTQLSVBS PRDM1_HUMAN Gene/Protein Processing [9]
TNF receptor-associated factor 2 (TRAF2) OT1MEZZN TRAF2_HUMAN Drug Response [9]
TNF receptor-associated factor 3 (TRAF3) OT5TQBGV TRAF3_HUMAN Drug Response [9]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Protein Interaction/Cellular Processes [9]
Molecular Interaction Atlas (MIA) 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) 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] [11]
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] [12]
Arn-509 DMT81LZ Major Increased metabolism of Ibrutinib caused by Arn-509 mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [13]
Gilteritinib DMTI0ZO Moderate Decreased clearance of Ibrutinib due to the transporter inhibition by Gilteritinib. Acute myeloid leukaemia [2A60] [13]
Pexidartinib DMS2J0Z Moderate Increased metabolism of Ibrutinib caused by Pexidartinib mediated induction of CYP450 enzyme. Bone/articular cartilage neoplasm [2F7B] [12]
Talazoparib DM1KS78 Moderate Decreased clearance of Ibrutinib due to the transporter inhibition by Talazoparib. Breast cancer [2C60-2C6Y] [14]
Tucatinib DMBESUA Major Decreased metabolism of Ibrutinib caused by Tucatinib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [15]
Lumacaftor DMCLWDJ Major Increased metabolism of Ibrutinib caused by Lumacaftor mediated induction of CYP450 enzyme. Cystic fibrosis [CA25] [13]
Vortioxetine DM6F1PU Moderate Increased risk of bleeding by the combination of Ibrutinib and Vortioxetine. Depression [6A70-6A7Z] [16]
Tazemetostat DMWP1BH Major Increased risk of bleeding by the combination of Ibrutinib and Tazemetostat. Follicular lymphoma [2A80] [17]
Ripretinib DM958QB Moderate Decreased clearance of Ibrutinib due to the transporter inhibition by Ripretinib. Gastrointestinal stromal tumour [2B5B] [15]
Avapritinib DMK2GZX Major Increased risk of bleeding by the combination of Ibrutinib and Avapritinib. Gastrointestinal stromal tumour [2B5B] [13]
Cobicistat DM6L4H2 Major Decreased metabolism of Ibrutinib caused by Cobicistat mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [15]
Epanova DMHEAGL Major Increased risk of bleeding by the combination of Ibrutinib and Epanova. Hyper-lipoproteinaemia [5C80] [18]
Ceritinib DMB920Z Major Decreased metabolism of Ibrutinib caused by Ceritinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [15]
PF-06463922 DMKM7EW Moderate Increased metabolism of Ibrutinib caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [12]
Idelalisib DM602WT Major Decreased metabolism of Ibrutinib caused by Idelalisib mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [15]
GDC-0199 DMH0QKA Major Decreased clearance of Ibrutinib due to the transporter inhibition by GDC-0199. Mature B-cell leukaemia [2A82] [15]
Arry-162 DM1P6FR Major Increased risk of bleeding by the combination of Ibrutinib and Arry-162. Melanoma [2C30] [17]
LGX818 DMNQXV8 Major Increased risk of bleeding by the combination of Ibrutinib and LGX818. Melanoma [2C30] [17]
Ubrogepant DM749I3 Moderate Decreased clearance of Ibrutinib due to the transporter inhibition by Ubrogepant. Migraine [8A80] [19]
Rimegepant DMHOAUG Moderate Decreased clearance of Ibrutinib due to the transporter inhibition by Rimegepant. Migraine [8A80] [20]
Siponimod DM2R86O Major Additive immunosuppressive effects by the combination of Ibrutinib and Siponimod. Multiple sclerosis [8A40] [15]
Ocrelizumab DMEZ2KH Moderate Additive immunosuppressive effects by the combination of Ibrutinib and Ocrelizumab. Multiple sclerosis [8A40] [21]
Fedratinib DM4ZBK6 Major Increased risk of bleeding by the combination of Ibrutinib and Fedratinib. Myeloproliferative neoplasm [2A20] [12]
Lefamulin DME6G97 Moderate Decreased clearance of Ibrutinib due to the transporter inhibition by Lefamulin. Pneumonia [CA40] [22]
Relugolix DMK7IWL Moderate Decreased clearance of Ibrutinib due to the transporter inhibition by Relugolix. Prostate cancer [2C82] [13]
Anthrax vaccine DM9GSWY Moderate Antagonize the effect of Ibrutinib when combined with Anthrax vaccine. Sepsis [1G40-1G41] [23]
Voxelotor DMCS6M5 Moderate Decreased metabolism of Ibrutinib caused by Voxelotor mediated inhibition of CYP450 enzyme. Sickle-cell disorder [3A51] [12]
Larotrectinib DM26CQR Moderate Decreased clearance of Ibrutinib due to the transporter inhibition by Larotrectinib. Solid tumour/cancer [2A00-2F9Z] [12]
Lusutrombopag DMH6IKO Moderate Decreased clearance of Ibrutinib due to the transporter inhibition by Lusutrombopag. Thrombocytopenia [3B64] [24]
Elagolix DMB2C0E Moderate Increased metabolism of Ibrutinib caused by Elagolix mediated induction of CYP450 enzyme. Uterine fibroid [2E86] [12]
Betrixaban DM2C4RF Major Increased risk of bleeding by the combination of Ibrutinib and Betrixaban. Venous thromboembolism [BD72] [17]
⏷ Show the Full List of 32 DDI Information of This Drug

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
⏷ 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 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.
11 Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
12 Product Information. Imbruvica (ibrutinib). Pharmacyclics Inc, Sunnyvale, CA.
13 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
14 Product Information. Talzenna (talazoparib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
15 Cerner Multum, Inc. "Australian Product Information.".
16 Alderman CP, Moritz CK, Ben-Tovim DI "Abnormal platelet aggregation associated with fluoxetine therapy." Ann Pharmacother 26 (1992): 1517-9. [PMID: 1482806]
17 Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
18 Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
19 Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
20 Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
21 Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
22 Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
23 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]
24 EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".