IBRUTINIB

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H24N6O2
Molecular Weight	440.4971
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=C2C(=NC=N1)N(N=C2C3=CC=C(OC4=CC=CC=C4)C=C3)[C@@H]5CCCN(C5)C(=O)C=C

InChI

InChIKey=XYFPWWZEPKGCCK-GOSISDBHSA-N

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

HIDE SMILES / InChI

Molecular Formula	C25H24N6O2
Molecular Weight	440.4971
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/205552Orig1s012lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/?term=23425038

Ibrutinib is an orally bioavailable Bruton's tyrosine kinase (BTK) inhibitor indicated for the treatment of mantle cell lymphoma (MCL) patients that previously received at least one therapy. The drug was jointly developed by Janssen Biotech and Pharmacyclics. Ibrutinib selectively binds to Cys-481 residue in the allosteric inhibitory segment of BTK (TK/SH1 domain), and irreversibly blocks its enzymatic activity thus preventing B-cell activation and signaling, totally blocking the B-cell receptor and cytokine receptor pathways. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. Apart from mantle cell lymphoma Ibrutinib is approved for the treatment of chronic lymphocytic leukemia and Waldenstrom Macroglobulinemia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tyrosine-protein kinase BTK 24 Target ID: Q06187 Gene ID: 695.0 Gene Symbol: BTK Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/205552Orig1s012lbl.pdf	Inhibitor 8504		0.5 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Mantle cell lymphoma 24 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/205552Orig1s012lbl.pdf	Primary	Approved 8583	IMBRUVICA Approved Use Indicated for the treatment of patients with: Mantle cell lymphoma (MCL) who have received at least one prior therapy; chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL); Waldenström's macroglobulinemia (WM). Launch Date 2013
Chronic lymphocytic leukemia 59 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/205552Orig1s012lbl.pdf	Primary	Approved 8583	IMBRUVICA Approved Use Indicated for the treatment of patients with: Mantle cell lymphoma (MCL) who have received at least one prior therapy; chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL); Waldenström's macroglobulinemia (WM). Launch Date 2013
Waldenström's macroglobulinemia 7 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/205552Orig1s012lbl.pdf	Primary	Approved 8583	IMBRUVICA Approved Use Indicated for the treatment of patients with: Mantle cell lymphoma (MCL) who have received at least one prior therapy; chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL); Waldenstrom Macroglobulinemia (WM). Launch Date 2013

C_max

Value	Dose	Analyte	Population
38.5 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156	420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered:	IBRUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
147 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156	420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered:	IBRUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
51.7 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156	420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered:	IBRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
120 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156	420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered:	IBRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Analyte	Population
1285 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01325701	560 mg 1 times / day multiple, oral dose: 560 mg route of administration: oral experiment type: multiple co-administered:	IBRUTINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
1485 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01325701	560 mg 1 times / day multiple, oral dose: 560 mg route of administration: oral experiment type: multiple co-administered:	PCI-45227 plasma	Homo sapiens population: unhealthy age: sex: food status:
1337 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01325701	840 mg 1 times / day multiple, oral dose: 840 mg route of administration: oral experiment type: multiple co-administered:	IBRUTINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
1671 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01325701	840 mg 1 times / day multiple, oral dose: 840 mg route of administration: oral experiment type: multiple co-administered:	PCI-45227 plasma	Homo sapiens population: unhealthy age: sex: food status:
561.6 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01646021	560 mg 1 times / day steady, oral dose: 560 mg route of administration: oral experiment type: steady co-administered:	IBRUTINIB plasma	Homo sapiens population: unhealthy age: sex: food status:
236 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156	420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered:	IBRUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
611 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156	420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered:	IBRUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
485 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156	420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered:	IBRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
864 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156	420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered:	IBRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Analyte	Population
9.7 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156	420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered:	IBRUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5.2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156	420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered:	IBRUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
11 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156	420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered:	IBRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4.5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25724156	420 mg single, oral dose: 420 mg route of administration: Oral experiment type: SINGLE co-administered:	IBRUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
2.7% EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391303/			IBRUTINIB plasma	Homo sapiens

Doses

Dose	Population	Adverse events
12.5 mg/kg 1 times / day steady, oral Highest studied dose Dose: 12.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 12.5 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23045577	unhealthy, 65 years (range: 41-82 years) Health Status: unhealthy Age Group: 65 years (range: 41-82 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/23045577	Other AEs: Diarrhea, Nausea... Other AEs: Diarrhea (grade 1-2, 3 patients) Nausea (grade 1-2, 2 patients) Vomiting (grade 1-2, 2 patients) Constipation (grade 1-2, 1 patient) Decreased appetite (grade 1-2, 1 patient) Dyspepsia (grade 1-2, 1 patient) Fatigue (grade 1-2, 4 patients) Headache (grade 1-2, 2 patients) Muscle spasms (grade 1-2, 3 patients) Myalgia (grade 1-2, 3 patients) Pyrexia (grade 1-2, 2 patients) Rash (grade 1-2, 1 patient) Cough (grade 1-2, 3 patients) Arthralgia (grade 1-2, 2 patients) Edema (grade 1-2, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/23045577
8.3 mg/kg 1 times / day steady, oral Dose: 8.3 mg/kg, 1 times / day Route: oral Route: steady Dose: 8.3 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23045578	unhealthy, 66 years (range: 41-82 years) Health Status: unhealthy Age Group: 66 years (range: 41-82 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/23045578	DLT: Hypersensitivity... Dose limiting toxicities: Hypersensitivity (grade 3, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/23045578
2.5 mg/kg 1 times / day steady, oral Dose: 2.5 mg/kg, 1 times / day Route: oral Route: steady Dose: 2.5 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23045579	unhealthy, 67 years (range: 41-82 years) Health Status: unhealthy Age Group: 67 years (range: 41-82 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/23045579	DLT: Neutropenia... Dose limiting toxicities: Neutropenia (grade 2, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/23045579
420 mg 1 times / day steady, oral Dose: 420 mg, 1 times / day Route: oral Route: steady Dose: 420 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26588924	unhealthy, 67.0 years (range: 56–71 years) Health Status: unhealthy Age Group: 67.0 years (range: 56–71 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/26588924	DLT: Pneumonia, Sepsis... Disc. AE: Stomatitis... Dose limiting toxicities: Pneumonia (grade 3) Sepsis (grade 3) AEs leading to discontinuation/dose reduction: Stomatitis (grade 3, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/26588924
560 mg 1 times / day steady, oral Recommended Dose: 560 mg, 1 times / day Route: oral Route: steady Dose: 560 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/205552s000lbl.pdf	unhealthy, 68 years (range: 40 - 84 years) Health Status: unhealthy Age Group: 68 years (range: 40 - 84 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/205552s000lbl.pdf	Disc. AE: Subdural hematoma, Neutropenia... Other AEs: Diarrhea, Diarrhea... AEs leading to discontinuation/dose reduction: Subdural hematoma (1.8%) Neutropenia (grade 3-4, 29%) Thrombocytopenia (grade 3-4, 17%) Anemia (grade 3-4, 9%) Other AEs: Diarrhea (grade 1-2, 46%) Diarrhea (grade 3-4, 5%) Nausea (grade 1-2, 31%) Constipation (grade 1-2, 25%) Abdominal pain (grade 1-2, 19%) Abdominal pain (grade 3-4, 5%) Vomiting (grade 1-2, 23%) Stomatitis (grade 1-2, 16%) Stomatitis (grade 3-4, 1%) Dyspepsia (grade 1-2, 11%) Upper respiratory tract infection (grade 1-2, 34%) Urinary tract infection (grade 1-2, 11%) Urinary tract infection (grade 3-4, 3%) Pneumonia (grade 1-2, 7%) Pneumonia (grade 3-4, 7%) Skin infection (grade 1-2, 9%) Skin infection (grade 3-4, 5%) Sinusitis (grade 1-2, 12%) Sinusitis (grade 3-4, 1%) Fatigue (grade 1-2, 36%) Fatigue (grade 3-4, 5%) Peripheral edema (grade 1-2, 32%) Peripheral edema (grade 3-4, 3%) Pyrexia (grade 1-2, 17%) Pyrexia (grade 3-4, 1%) Asthenia (grade 1-2, 11%) Asthenia (grade 3-4, 3%) Bruising (grade 1-2, 30%) Rash (grade 1-2, 22%) Rash (grade 3-4, 3%) Petechiae (grade 1-2, 11%) Musculoskeletal pain (grade 1-2, 36%) Musculoskeletal pain (grade 3-4, 1%) Muscle spasms (grade 1-2, 14%) Arthralgia (grade 1-2, 11%) Dyspnea (grade 1-2, 23%) Dyspnea (grade 3-4, 4%) Cough (grade 1-2, 19%) Epistaxis (grade 1-2, 11%) Decreased appetite (grade 1-2, 19%) Decreased appetite (grade 3-4, 2%) Dehydration (grade 1-2, 8%) Dehydration (grade 3-4, 4%) Dizziness (grade 1-2, 14%) Headache (grade 1-2, 13%) Platelets decreased (grade 1-2, 40%) Platelets decreased (grade 3-4, 17%) Neutrophil count decreased (grade 1-2, 18%) Neutrophil count decreased (grade 3-4, 29%) Hemoglobin decreased (grade 1-2, 32%) Hemoglobin decreased (grade 3-4, 9%) Hyperuricemia (15%) Hemorrhage (grade 3, 5%) Infection (grade 3, 25%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/205552s000lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inducer 1087	substrate 1193 inhibitor 2438	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2B2 1 CYP2C8 1057 CYP2C19 2057 CYP2E1 1060 CYP3A4/5 296 P-gp 1741	CYP3A4/5 91 CYP1A2 1197 CYP2A6 626 CYP2B6 776 CYP2C8 810 CYP2C19 1119 P-gp 2052	CYP1A2 832 CYP2B6 669

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	no [Ki 4.8 uM]
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	no
CYP3A4/5 357	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	weak [Ki 10 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	weak [Ki 12 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	weak [Ki 12.5 uM]
CYP2B2 16	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	weak [Ki 4.8 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	weak [Ki 5.9 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	weak [Ki 6.6 uM]
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=24 Page: 24.0	yes [IC50 4.9 uM]
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	yes	PCI-45227 1
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	yes	PCI-45227 1
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	yes	PCI-45227 1

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=9 Page: -	major	yes (co-administration study) Comment: In a dedicated drug-interaction trial, concomitant ketoconazole (strong CYP3A4 inhibitor) increased ibrutinib Cmax 29-fold and AUC 24-fold. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=9 Page: -
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=36 Page: 36.0	no [Ki >100 uM]
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=36 Page: -	no
CYP2A6 626	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=36 Page: -	no
CYP2B6 776	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=36 Page: -	no
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=36 Page: -	no
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=36 Page: -	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=43 Page: 43.0	no
CYP3A4/5 91	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=34 Page: -	yes
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=34 Page: -	yes	yes (pharmacogenomic study) Comment: n the mass balance trial (n = 6), the mean ibrutinib and the active metabolite PCI-45227 AUCs were 10% and 29% higher, respectively in CYP2D6 poor metabolizers (PMs, N=2) compared with the mean AUCs in CYP2D6 extensive metabolizers (EMs, N=4). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=34 Page: -

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=19 Page: 19.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:76612	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:76612
ChemicalBook	CB12515873	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB12515873
MolPort	MolPort-027-806-955	https://www.molport.com/shop/molecule-link/MolPort-027-806-955
ZINC	ZINC000035328014	http://zinc15.docking.org/substances/ZINC000035328014

PubMed

Title	Date	PubMed
Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib.	2015-09-24	26254443
Ibrutinib in pretreated Waldenström's macroglobulinaemia.	2015-05	25892147
Ibrutinib: a review of its use in patients with mantle cell lymphoma or chronic lymphocytic leukaemia.	2015-05	25802231
Absorption, metabolism, and excretion of oral ¹⁴C radiolabeled ibrutinib: an open-label, phase I, single-dose study in healthy men.	2015-02	25488930
Blockade of oncogenic IκB kinase activity in diffuse large B-cell lymphoma by bromodomain and extraterminal domain protein inhibitors.	2014-08-05	25049379
Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765).	2013-11	23425038
Ibrutinib: a novel Bruton's tyrosine kinase inhibitor with outstanding responses in patients with chronic lymphocytic leukemia.	2013-08	23617325
Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia.	2013-07-04	23782158
Ibrutinib: a strong candidate for the future of mantle cell lymphoma treatment.	2013-06	23730878
Ibrutinib (PCI-32765), the first BTK (Bruton's tyrosine kinase) inhibitor in clinical trials.	2013-03	23296407
Bruton's tyrosine kinase inhibitors: approaches to potent and selective inhibition, preclinical and clinical evaluation for inflammatory diseases and B cell malignancies.	2012-05-24	22394077
Discovery of selective irreversible inhibitors for Bruton's tyrosine kinase.	2007-01	17154430

Patents

Sample Use Guides

In Vivo Use Guide

MCL: 560 mg taken orally once daily (four 140 mg capsules once daily); CLL/SLL and WM: 420 mg taken orally once daily (three 140 mg capsules once daily). Capsules should be taken orally with a glass of water.

Route of Administration: Oral

In Vitro Use Guide

CLL-B cells were freshly isolated from the peripheral blood of the CLL patients before the initiation of ibrutinib therapy, cultured in vitro for 72 h in the presence or absence of ibrutinib, and analyzed with annexin V and 7AAD double staining. CLL cells were cultured alone in the presence or absence of various concentrations of ibrutinib from 0.01 to 10 uM.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 20:07:07 GMT 2025` Edited by `admin` on `Mon Mar 31 20:07:07 GMT 2025`
Record UNII	1X70OSD4VX
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

IBRUTINIB

Official Name

English

IMBRUVICA

Preferred Name

English

Ibrutinib [WHO-DD]

Common Name

English

PCI-32765

Code

English

PCI-32765-00

Code

English

IBRUTINIB [VANDF]

Common Name

English

IBRUTINIB [ORANGE BOOK]

Common Name

English

2-PROPEN-1-ONE, 1-((3R)-3-(4-AMINO-3-(4-PHENOXYPHENYL)-1H-PYRAZOLO(3,4-D)PYRIMIDIN-1-YL)-1-PIPERIDINYL)-

Systematic Name

English

IBRUTINIB [JAN]

Common Name

English

IBRUTINIB [USAN]

Common Name

English

IBRUTINIB [MI]

Common Name

English

PC-32765

Code

English

PCI 32765

Code

English

1-{(3R)-3-[4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1- yl}prop-2-en-1-one

Systematic Name

English

CRA-032765

Code

English

ibrutinib [INN]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

462314