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 8297		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 8429	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 8429	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 8429	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 blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
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 blood	Homo sapiens population: UNHEALTHY 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 blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
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 blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Analyte	Population
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 blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
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 blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
6100 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 blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
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 blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
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:
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 unknown	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 unknown	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 unknown	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 unknown	Homo sapiens population: unhealthy age: sex: food status:

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 blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
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 blood	Homo sapiens population: UNHEALTHY 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 blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
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 blood	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) n = 7 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 65 years (range: 41-82 years) Sex: M+F Population Size: 7 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) n = 8 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 66 years (range: 41-82 years) Sex: M+F Population Size: 8 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) n = 9 Health Status: unhealthy Condition: relapsed/refractory B-cell malignancies Age Group: 67 years (range: 41-82 years) Sex: M+F Population Size: 9 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 Condition: chronic lymphocytic leukemia \| small lymphocytic lymphoma 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) n = 111 Health Status: unhealthy Condition: mantle cell lymphoma Age Group: 68 years (range: 40 - 84 years) Sex: M+F Population Size: 111 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 1737 inducer 781	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2B2 1 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP3A4/5 278 P-gp 1461	CYP3A4/5 85 CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2C19 991 P-gp 1537	CYP1A2 701 CYP2B6 547

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	no [Ki 4.8 uM]
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	no
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	weak [Ki 10 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	weak [Ki 12 uM]
CYP2D6 1891	inhibitor 3277 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 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	weak [Ki 4.8 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	weak [Ki 5.9 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	weak [Ki 6.6 uM]
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=24 Page: 24.0	yes [IC50 4.9 uM]
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	yes	PCI-45227 1
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=42 Page: 42.0	yes	PCI-45227 1
CYP3A4 1925	inducer 1573 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 1737	substrate 3367 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 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=36 Page: 36.0	no [Ki >100 uM]
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=36 Page: -	no
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=36 Page: -	no
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=36 Page: -	no
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=36 Page: -	no
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=36 Page: -	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=43 Page: 43.0	no
CYP3A4/5 85	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205552Orig2s000ClinPharmR.pdf#page=34 Page: -	yes
CYP2D6 1217	substrate 3367 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 1647	inhibitor 1626 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
		252160516
Discovery of selective irreversible inhibitors for Bruton's tyrosine kinase.	2007 Jan	17154430
Bruton's tyrosine kinase inhibitors: approaches to potent and selective inhibition, preclinical and clinical evaluation for inflammatory diseases and B cell malignancies.	2012 May 24	22394077
Ibrutinib: a novel Bruton's tyrosine kinase inhibitor with outstanding responses in patients with chronic lymphocytic leukemia.	2013 Aug	23617325
Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia.	2013 Jul 4	23782158
Ibrutinib: a strong candidate for the future of mantle cell lymphoma treatment.	2013 Jun	23730878
Ibrutinib (PCI-32765), the first BTK (Bruton's tyrosine kinase) inhibitor in clinical trials.	2013 Mar	23296407
Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765).	2013 Nov	23425038
Blockade of oncogenic IκB kinase activity in diffuse large B-cell lymphoma by bromodomain and extraterminal domain protein inhibitors.	2014 Aug 5	25049379
Absorption, metabolism, and excretion of oral ¹⁴C radiolabeled ibrutinib: an open-label, phase I, single-dose study in healthy men.	2015 Feb	25488930
Ibrutinib in pretreated Waldenström's macroglobulinaemia.	2015 May	25892147
Ibrutinib: a review of its use in patients with mantle cell lymphoma or chronic lymphocytic leukaemia.	2015 May	25802231
Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib.	2015 Sep 24	26254443

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 `Fri Dec 15 20:18:17 GMT 2023` Edited by `admin` on `Fri Dec 15 20:18:17 GMT 2023`
Record UNII	1X70OSD4VX
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

IBRUTINIB

Official Name

English

Ibrutinib [WHO-DD]

Common Name

English

PCI-32765

Code

English

PCI-32765-00

Code

English

IBRUTINIB [VANDF]

Common Name

English

IMBRUVICA

Brand 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