BOSUTINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C26H29Cl2N5O3
Molecular Weight	530.447
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1CCN(CCCOc2cc3c(cc2OC)c(=Nc4cc(c(cc4Cl)Cl)OC)c(C#N)c[nH]3)CC1

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

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 5 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 7701		1.2 nM [IC50]
Tyrosine-protein kinase ABL1 5 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 7701		1.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Leukemia, myelogenous, chronic, BCR-ABL positive 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203469lbl.pdf	Primary		Approved 7997	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 1470 inhibitor 1172 inducer 657	substrate 865 inhibitor 1318 inducer 343	inhibitor 1421	inhibitor 1360

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1089 CYP2C19 1215	P-gp 1223 CYP1A2 892 CYP2A6 452 CYP2B6 575 CYP2C8 586 CYP2E1 567	CYP1A2 618 CYP2B6 486 CYP2C19 260

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1406	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2B6 845	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C19 1277	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C9 1362	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C9 1362	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP3A4 1462	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
P-gp 1255	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	yes [IC50 2 uM]
CYP2D6 1455	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	yes [Ki 10 uM]
CYP2C19 1277	inhibitor 2614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	yes [Ki 27 uM]
CYP3A4 1462	inhibitor 2614 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 1470	substrate 2752 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 892	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2A6 452	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2B6 575	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C8 586	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C9 865	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2E1 567	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
P-gp 1223	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1392	inhibitor 1374 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
The next generation of therapies for chronic myeloid leukemia.	2009	20007109
Standard management of patients with chronic myeloid leukemia.	2009	20007107
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
Valproic acid enhances bosutinib cytotoxicity in colon cancer cells.	2009 Apr 15	19123474
[Synthesis and biological evaluation of 3-quinolinecarbonitrile-7-amide derivatives].	2009 Aug	20055156
Targeted treatment of imatinib-resistant chronic myeloid leukemia: Focus on dasatinib.	2009 Feb 18	20616897
Targeted treatment of chronic myeloid leukemia: role of imatinib.	2009 Feb 18	20616895
The structure of the leukemia drug imatinib bound to human quinone reductase 2 (NQO2).	2009 Feb 24	19236722
[Development of novel tyrosine kinase inhibitors for treatment of imatinib-resistant CML patients].	2009 Jul	19638722
Tyrosine kinase inhibitor-induced platelet dysfunction in patients with chronic myeloid leukemia.	2009 Jul 9	19414863
New mechanisms of resistance in Philadelphia chromosome acute lymphoblastic leukemia.	2009 Jun	21082971
Efficacy and pharmacodynamic effects of bosutinib (SKI-606), a Src/Abl inhibitor, in freshly generated human pancreas cancer xenografts.	2009 Jun	19509264
Src activation in melanoma and Src inhibitors as therapeutic agents in melanoma.	2009 Jun	19434004
Impact of tyrosine kinase inhibitors on patient outcomes in Philadelphia chromosome-positive acute lymphoblastic leukaemia.	2009 Jun	19388927
Bosutinib: a dual SRC/ABL kinase inhibitor for the treatment of chronic myeloid leukemia.	2009 Oct	21083014
New targets for Ph+ leukaemia therapy.	2009 Sep	19959093
Advances in the biology and therapy of patients with chronic myeloid leukaemia.	2009 Sep	19959090
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
Danusertib (formerly PHA-739358)--a novel combined pan-Aurora kinases and third generation Bcr-Abl tyrosine kinase inhibitor.	2010	20072840
Bosutinib.	2010	20072835
Lung adenocarcinoma cells floating in lymphatic vessels resist anoikis by expressing phosphorylated Src.	2010 Apr	20146241
SRC kinase inhibition: targeting bone metastases and tumor growth in prostate and breast cancer.	2010 Apr	20015594
Molecular mechanisms of acquired resistance to tyrosine kinase targeted therapy.	2010 Apr 12	20385023
[Development of ABL tyrosine kinase inhibitors].	2010 Aug	20805664
Bosutinib: a review of preclinical studies in chronic myelogenous leukaemia.	2010 Jul	20399641
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
Synergistic activity of the Src/Abl inhibitor bosutinib in combination with imatinib.	2010 Jun	20445575
Synthesis of bosutinib from 3-methoxy-4-hydroxybenzoic acid.	2010 Jun 11	20657439
The dual kinase complex FAK-Src as a promising therapeutic target in cancer.	2010 Jun 24	20616959
Inhibition of Ser/Thr phosphatases induces capacitation-associated signaling in the presence of Src kinase inhibitors.	2010 Mar 12	20068039
New developments in tyrosine kinase inhibitor therapy for newly diagnosed chronic myeloid leukemia.	2010 Mar 15	20197479
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
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
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
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.

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

BOSUTINIB [WHO-DD]

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

Classification Tree Code System Code

WHO-ATC

L01XE14