BOSUTINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C26H29Cl2N5O3
Molecular Weight	530.446
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(Cl)C=C(Cl)C(NC2=C(C=NC3=CC(OCCCN4CCN(C)CC4)=C(OC)C=C23)C#N)=C1

InChI

InChIKey=UBPYILGKFZZVDX-UHFFFAOYSA-N

InChI=1S/C26H29Cl2N5O3/c1-32-6-8-33(9-7-32)5-4-10-36-25-13-21-18(11-24(25)35-3)26(17(15-29)16-30-21)31-22-14-23(34-2)20(28)12-19(22)27/h11-14,16H,4-10H2,1-3H3,(H,30,31)

HIDE SMILES / InChI

Molecular Formula	C26H29Cl2N5O3
Molecular Weight	530.446
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203341s005lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.drugdevelopment-technology.com/projects/bosutinib-leukaemia/; http://www.pharmacodia.com/yaodu/html/v1/chemicals/d6bcb486f72ae7b5dc68b5b7df7ec887.html

Bosutinib (trade name Bosulif) originally synthesized by Wyeth, it is being developed by Pfizer. Bosutinib received US FDA and EU European Medicines Agency approval on September 4, 2012 and 27 March 2013 respectively for the treatment of adult patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance, or intolerance to prior therapy. Bosutinib is a synthetic quinolone derivative and dual kinase inhibitor that targets both Abl and Src kinases with potential antineoplastic activity. Unlike imatinib, bosutinib inhibits the autophosphorylation of both Abl and Src kinases, resulting in inhibition of cell growth and apoptosis. Because of the dual mechanism of action, this agent may have activity in resistant CML disease, other myeloid malignancies and solid tumors. Abl kinase is upregulated in the presence of the abnormal Bcr-abl fusion protein which is commonly associated with chronic myeloid leukemia (CML). Overexpression of specific Src kinases is also associated with the imatinib-resistant CML phenotype.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Proto-oncogene tyrosine-protein kinase Src 7 Target ID: P12931 Gene ID: 6714.0 Gene Symbol: SRC Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203341s005lbl.pdf	Inhibitor 8228		1.2 nM [IC50]
Tyrosine-protein kinase ABL1 7 Target ID: P00519 Gene ID: 25.0 Gene Symbol: ABL1 Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203341s005lbl.pdf	Inhibitor 8228		1.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Leukemia, myelogenous, chronic, BCR-ABL positive 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203469lbl.pdf	Primary		Approved 8360	BOSULIF Approved Use Indicated for the treatment of adult patients with chronic, accelerated, or blast phase Ph+ chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy. Launch Date 1.33392957E12

C_max

Value	Dose	Analyte	Population
62.1 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27113346	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
88 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27113346	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
200 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203341lbl.pdf	500 mg 1 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
125 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
182.425 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
200 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203341lbl.pdf	500 mg 1 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	BOSUTINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
216 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB unknown	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: HIGH-FAT

AUC

Value	Dose	Analyte	Population
1150 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27113346	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
1768 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27113346	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
3650 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203341lbl.pdf	500 mg 1 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
2950 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
3160 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3650 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203341lbl.pdf	500 mg 1 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	BOSUTINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
4000 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB unknown	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: HIGH-FAT

T_1/2

Value	Dose	Analyte	Population
39.1 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27113346	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
32.4 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27113346	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
21.9 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
21.4 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
22.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203341lbl.pdf	500 mg 1 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	BOSUTINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
33.8 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB unknown	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: HIGH-FAT

F_unbound

Value	Dose	Co-administered	Analyte	Population
4% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203341lbl.pdf	500 mg 1 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:		BOSUTINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
4% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203341lbl.pdf	500 mg 1 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		BOSUTINIB unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED

Doses

Dose	Population	Adverse events
500 mg 1 times / day steady, oral Recommended Dose: 500 mg, 1 times / day Route: oral Route: steady Dose: 500 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000MedR.pdf	unhealthy, 18-91 years n = 571 Health Status: unhealthy Age Group: 18-91 years Sex: M+F Population Size: 571 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000MedR.pdf	Disc. AE: Thrombocytopenia, Elevated liver enzymes... AEs leading to discontinuation/dose reduction: Thrombocytopenia (29 patients) Elevated liver enzymes (17 patients) Neutropenia (11 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000MedR.pdf
800 mg single, oral Dose: 800 mg Route: oral Route: single Dose: 800 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	healthy, adult n = 5 Health Status: healthy Age Group: adult Population Size: 5 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf
600 mg 1 times / day steady, oral Dose: 600 mg, 1 times / day Route: oral Route: steady Dose: 600 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	unhealthy n = 2 Health Status: unhealthy Condition: advanced malignant solid tumors Population Size: 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf

AEs

AE	Significance	Dose	Population
Neutropenia	11 patient Disc. AE	500 mg 1 times / day steady, oral Recommended Dose: 500 mg, 1 times / day Route: oral Route: steady Dose: 500 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000MedR.pdf	unhealthy, 18-91 years n = 571 Health Status: unhealthy Age Group: 18-91 years Sex: M+F Population Size: 571 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000MedR.pdf
Elevated liver enzymes	17 patients Disc. AE	500 mg 1 times / day steady, oral Recommended Dose: 500 mg, 1 times / day Route: oral Route: steady Dose: 500 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000MedR.pdf	unhealthy, 18-91 years n = 571 Health Status: unhealthy Age Group: 18-91 years Sex: M+F Population Size: 571 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000MedR.pdf
Thrombocytopenia	29 patients Disc. AE	500 mg 1 times / day steady, oral Recommended Dose: 500 mg, 1 times / day Route: oral Route: steady Dose: 500 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000MedR.pdf	unhealthy, 18-91 years n = 571 Health Status: unhealthy Age Group: 18-91 years Sex: M+F Population Size: 571 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000MedR.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709 inhibitor 1579 inducer 768	substrate 1010 inhibitor 1752 inducer 383	inhibitor 1837	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1437 CYP2C19 1463	P-gp 1527 CYP1A2 1032 CYP2A6 523 CYP2B6 660 CYP2C8 688 CYP2E1 648	CYP1A2 689 CYP2B6 538 CYP2C19 290

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1673	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2B6 985	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C19 1537	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C9 1803	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP3A4 1909	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
P-gp 1626	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	yes [IC50 2 uM]
CYP2D6 1875	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	yes [Ki 10 uM]
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	yes [Ki 27 uM]
CYP3A4 1909	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	yes [Ki 27 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1709	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	major	yes (co-administration study) Comment: ketoconazole increased cmax of bosutinib by 5x, auc by 9x Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf
CYP1A2 1032	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2A6 523	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2B6 660	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C8 688	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C9 1010	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2E1 648	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
P-gp 1527	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1632	inhibitor 1613 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000PharmR.pdf

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:39112	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:39112
ChemicalBook	CB22673646	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB22673646
MolPort	MolPort-008-155-956	https://www.molport.com/shop/molecule-link/MolPort-008-155-956
Selleck Chemicals	Bosutinib	http://www.selleckchem.com/products/Bosutinib.html
ZINC	ZINC000022448983	http://zinc15.docking.org/substances/ZINC000022448983
eMolecules	31507652	https://www.emolecules.com/cgi-bin/more?vid=31507652

PubMed

Title	Date	PubMed
In vitro and in vivo activity of SKI-606, a novel Src-Abl inhibitor, against imatinib-resistant Bcr-Abl+ neoplastic cells.	2006 Dec 1	17114238
SKI-606 decreases growth and motility of colorectal cancer cells by preventing pp60(c-Src)-dependent tyrosine phosphorylation of beta-catenin and its nuclear signaling.	2006 Feb 15	16489032
Kinase inhibitors in chronic myelogenous leukemia.	2006 May	16728945
Structural insights into the ATP binding pocket of the anaplastic lymphoma kinase by site-directed mutagenesis, inhibitor binding analysis, and homology modeling.	2006 Sep 21	16970400
Persistent Cdk2 inactivation drives growth arrest of BCR-ABL-expressing cells in response to dual inhibitor of SRC and ABL kinases SKI606.	2007 Jul	17129604
Management of patients with resistant or refractory chronic myelogenous leukemia.	2008 Apr 15	18472616
Tailoring tyrosine kinase inhibitor therapy to tackle specific BCR-ABL1 mutant clones.	2008 Aug	18242697
The design, synthesis and biological evaluation of 7-alkoxy-4-heteroarylamino-3-cyanoquinolines as dual inhibitors of c-Src and iNOS.	2008 Dec 1	18930653
Therapeutic options for chronic myeloid leukemia: focus on imatinib (Glivec, Gleevectrade mark).	2008 Feb	18728706
Targeted therapy in chronic myeloid leukemia.	2008 Jan	18095887
Beyond dose escalation: clinical options for relapse or resistance in chronic myelogenous leukemia.	2008 Mar	18397678
SKI-606 (bosutinib), a novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells.	2008 May	18483306
Improving Response Rates to EGFR-Targeted Therapies for Head and Neck Squamous Cell Carcinoma: Candidate Predictive Biomarkers and Combination Treatment with Src Inhibitors.	2009	19636423
Second-generation tyrosine kinase inhibitors in the post-transplant period in patients with chronic myeloid leukemia or Philadelphia-positive acute lymphoblastic leukemia.	2009	19602874
Increased levels of active c-Src distinguish invasive from in situ lobular lesions.	2009	19583841
Building bridges from 'omics' to cell biology.	2009	19291275
Dasatinib in chronic myeloid leukemia: a review.	2009 Apr	19536317
Targeted treatment of imatinib-resistant chronic myeloid leukemia: Focus on dasatinib.	2009 Feb 18	20616897
Severe toxicity of skin rash, fever and diarrhea associated with imatinib: case report and review of skin toxicities associated with tyrosine kinase inhibitors.	2009 Feb 6	19920908
New mechanisms of resistance in Philadelphia chromosome acute lymphoblastic leukemia.	2009 Jun	21082971
Impact of tyrosine kinase inhibitors on patient outcomes in Philadelphia chromosome-positive acute lymphoblastic leukaemia.	2009 Jun	19388927
New targets for Ph+ leukaemia therapy.	2009 Sep	19959093
Danusertib (formerly PHA-739358)--a novel combined pan-Aurora kinases and third generation Bcr-Abl tyrosine kinase inhibitor.	2010	20072840
Bosutinib.	2010	20072835
Tyrosine kinase inhibitors: the first decade.	2010 Apr	20425399
Lung adenocarcinoma cells floating in lymphatic vessels resist anoikis by expressing phosphorylated Src.	2010 Apr	20146241
[Development of ABL tyrosine kinase inhibitors].	2010 Aug	20805664
SRC: a century of science brought to the clinic.	2010 Aug	20689754
A type-II kinase inhibitor capable of inhibiting the T315I "gatekeeper" mutant of Bcr-Abl.	2010 Aug 12	20604564
A comprehensive target selectivity survey of the BCR-ABL kinase inhibitor INNO-406 by kinase profiling and chemical proteomics in chronic myeloid leukemia cells.	2010 Jan	19890374
Src inhibitors in lung cancer: current status and future directions.	2010 Jul 1	20630825
Advances in targeting SRC in the treatment of breast cancer and other solid malignancies.	2010 Jul 15	20634194
Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins.	2010 Jul 21	20663135
The dual kinase complex FAK-Src as a promising therapeutic target in cancer.	2010 Jun 24	20616959
New developments in tyrosine kinase inhibitor therapy for newly diagnosed chronic myeloid leukemia.	2010 Mar 15	20197479
Optimization of 7-alkene-3-quinolinecarbonitriles as Src kinase inhibitors.	2010 May 1	20363128
Molecular measurement of BCR-ABL transcript variations in chronic myeloid leukemia patients in cytogenetic remission.	2010 Nov 18	21087500
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.	2010 Nov 24	21095574
Molecular characterization of c-Abl/c-Src kinase inhibitors targeted against murine tumour progenitor cells that express stem cell markers.	2010 Nov 30	21152443
Comprehensive analysis of kinase inhibitor selectivity.	2011 Oct 30	22037378
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.	2011 Oct 30	22037377
Development and validation of a high-throughput intrinsic ATPase activity assay for the discovery of MEKK2 inhibitors.	2013 Apr	23134735

Patents

Sample Use Guides

In Vivo Use Guide

Recommended Dose: 500 mg orally once daily with food. Consider dose escalation to 600 mg daily in patients who do not reach complete hematologic response by week 8 or complete cytogenetic response by week 12 and do not have Grade 3 or greater adverse reactions.

Route of Administration: Oral

In Vitro Use Guide

Bosutinib potently inhibits Src-dependent cell proliferation with an IC50 of 100 nM.

Substance Class	Chemical Created by `admin` on `Thu Jul 06 00:41:34 UTC 2023` Edited by `admin` on `Thu Jul 06 00:41:34 UTC 2023`
Record UNII	5018V4AEZ0
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

BOSUTINIB

Official Name

English

BOSUTINIB [USAN]

Common Name

English

BOSULIF

Common Name

English

BOSUTINIB [MI]

Common Name

English

SK-606

Code

English

BOSUTINIB [MART.]

Common Name

English

3-QUINOLINECARBONITRILE, 4-((2,4-DICHLORO-5-METHOXYPHENYL)AMINO)-6-METHYL-1-PIPERAZINYL)PROPOXY)-

Common Name

English

4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile

Systematic Name

English

BOSUTINIB [VANDF]

Common Name

English

SKI-606

Code

English

bosutinib [INN]

Common Name

English

Bosutinib [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-ATC

L01XE14