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 8297		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 8297		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 8429	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 2012

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 1737 inhibitor 1587 inducer 781	substrate 1037 inhibitor 1767 inducer 389	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 CYP2C19 1478	P-gp 1537 CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2E1 667	CYP1A2 701 CYP2B6 547 CYP2C19 293

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	yes [IC50 2 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	yes [Ki 10 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	yes [Ki 27 uM]
CYP3A4 1925	inhibitor 3277 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 1737	substrate 3367 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 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 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
Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity.	2001 Nov 8	11689083
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
Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors.	2007 Sep	17721511
Tailoring tyrosine kinase inhibitor therapy to tackle specific BCR-ABL1 mutant clones.	2008 Aug	18242697
Effective and selective inhibition of chronic myeloid leukemia primitive hematopoietic progenitors by the dual Src/Abl kinase inhibitor SKI-606.	2008 Feb 15	18056843
Targeted therapy in chronic myeloid leukemia.	2008 Jan	18095887
Src inhibition ameliorates polycystic kidney disease.	2008 Jul	18385429
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
P-loop mutations and novel therapeutic approaches for imatinib failures in chronic myeloid leukemia.	2008 Oct 1	18828913
The next generation of therapies for chronic myeloid leukemia.	2009	20007109
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
Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells.	2009 Mar	19039322
Bosutinib: a dual SRC/ABL kinase inhibitor for the treatment of chronic myeloid leukemia.	2009 Oct	21083014
Acid elution and one-dimensional shotgun analysis on an Orbitrap mass spectrometer: an application to drug affinity chromatography.	2009 Oct	19653696
New targets for Ph+ leukaemia therapy.	2009 Sep	19959093
Imatinib and beyond--exploring the full potential of targeted therapy for CML.	2009 Sep	19652654
Fyn kinase activity is required for normal organization and functional polarity of the mouse oocyte cortex.	2009 Sep	19363790
Efficacy of dasatinib for the treatment of intractable chronic myeloid leukemia.	2010	22282699
Locking Src/Abl Tyrosine Kinase Activities Regulate Cell Differentiation and Invasion of Human Cervical Cancer Cells Expressing E6/E7 Oncoproteins of High-Risk HPV.	2010	20862378
Danusertib (formerly PHA-739358)--a novel combined pan-Aurora kinases and third generation Bcr-Abl tyrosine kinase inhibitor.	2010	20072840
Bosutinib.	2010	20072835
SRC: a century of science brought to the clinic.	2010 Aug	20689754
Optimizing combination therapies with existing and future CML drugs.	2010 Aug 23	20808800
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
Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins.	2010 Jul 21	20663135
SKI-606 (Bosutinib) blocks prostate cancer invasion, growth, and metastasis in vitro and in vivo through regulation of genes involved in cancer growth and skeletal metastasis.	2010 May	20423991
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
First-line treatment for chronic myeloid leukemia: dasatinib, nilotinib, or imatinib.	2010 Nov 26	21108851
Molecular characterization of c-Abl/c-Src kinase inhibitors targeted against murine tumour progenitor cells that express stem cell markers.	2010 Nov 30	21152443
[SRC kinases in tumor therapy].	2010 Oct	20981590
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
LRIG1 modulates cancer cell sensitivity to Smac mimetics by regulating TNFα expression and receptor tyrosine kinase signaling.	2012 Mar 1	22241084
Novel aspects of therapy with the dual Src and Abl kinase inhibitor bosutinib in chronic myeloid leukemia.	2012 Sep	23098112
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 `Fri Dec 15 17:20:55 GMT 2023` Edited by `admin` on `Fri Dec 15 17:20:55 GMT 2023`
Record UNII	5018V4AEZ0
Record Status	`Validated (UNII)`
Record Version

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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