Bosutinib methanoate

Details

Stereochemistry	ACHIRAL
Molecular Formula	C26H29Cl2N5O3.CH4O
Molecular Weight	562.488
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=KBLGKECLADKUHT-UHFFFAOYSA-N

InChI=1S/C26H29Cl2N5O3.CH4O/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;1-2/h11-14,16H,4-10H2,1-3H3,(H,30,31);2H,1H3

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

Molecular Formula	CH4O
Molecular Weight	32.0419
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 8 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 8504		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 8504		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 8583	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
273 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	500 mg 1 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
190 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
76.6 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
95.4 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
19.6 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
6.9 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4.89 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
17 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
43.1 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
63.7 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
117 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
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 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
206 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	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 multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
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 plasma	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 plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: HIGH-FAT
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 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
278.12 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 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
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

AUC

Value	Dose	Analyte	Population
3580 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	500 mg 1 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2900 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1170 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1670 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
329 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
114 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
129 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
284 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
920 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1200 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2340 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
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 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4300 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	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 multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE 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 steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	BOSUTINIB plasma	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 plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: HIGH-FAT
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 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
4084.7 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 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
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

T_1/2

Value	Dose	Analyte	Population
23.3 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	500 mg 1 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
19.89 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
19.4 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
30 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
64.7 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
25.8 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
12.9 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
18.6 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
20.79 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
17.1 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
18.6 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
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 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
19.9 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	BOSUTINIB plasma	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 plasma	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 plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: HIGH-FAT
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 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
15.4 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 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
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

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 plasma	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 plasma	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 Health Status: unhealthy Age Group: 18-91 years Sex: M+F 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 Health Status: healthy Age Group: adult 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 Health Status: unhealthy 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 Health Status: unhealthy Age Group: 18-91 years Sex: M+F 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 Health Status: unhealthy Age Group: 18-91 years Sex: M+F 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 Health Status: unhealthy Age Group: 18-91 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000MedR.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252 inducer 1087	substrate 1193 inhibitor 2438 inducer 440	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 CYP2C19 2057	P-gp 2052 CYP1A2 1197 CYP2A6 626 CYP2B6 776 CYP2C8 810 CYP2E1 729	CYP1A2 832 CYP2B6 669 CYP2C19 329

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C19 2141	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	yes [IC50 2 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	yes [Ki 10 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	yes [Ki 27 uM]
CYP3A4 2633	inhibitor 4027 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 1946	substrate 4014 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 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2A6 626	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2B6 776	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
CYP2E1 729	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203341Orig1s000ClinPharmR.pdf	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 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
eMolecules	31507652	https://www.emolecules.com/cgi-bin/more?vid=31507652
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

PubMed

Title	Date	PubMed
NS-187 (INNO-406), a Bcr-Abl/Lyn dual tyrosine kinase inhibitor.	2007 Nov 14	19662183
Targeted drugs in chronic myeloid leukemia.	2008	19075651
Novel agents in CML therapy: tyrosine kinase inhibitors and beyond.	2008	19074121
Gateways to clinical trials.	2008 Apr	18597009
Management of patients with resistant or refractory chronic myelogenous leukemia.	2008 Apr 15	18472616
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
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
Characterization of compound 584, an Abl kinase inhibitor with lasting effects.	2008 May	18367480
Abl tyrosine kinase inhibitors for overriding Bcr-Abl/T315I: from the second to third generation.	2008 Sep	18759691
The next generation of therapies for chronic myeloid leukemia.	2009	20007109
Standard management of patients with chronic myeloid leukemia.	2009	20007107
Increased levels of active c-Src distinguish invasive from in situ lobular lesions.	2009	19583841
[Synthesis and biological evaluation of 3-quinolinecarbonitrile-7-amide derivatives].	2009 Aug	20055156
Neuroprotective profile of novel SRC kinase inhibitors in rodent models of cerebral ischemia.	2009 Dec	19741150
Targeted treatment of chronic myeloid leukemia: role of imatinib.	2009 Feb 18	20616895
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
Activity of bosutinib, dasatinib, and nilotinib against 18 imatinib-resistant BCR/ABL mutants.	2009 Jan 20	19075254
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
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
Acid elution and one-dimensional shotgun analysis on an Orbitrap mass spectrometer: an application to drug affinity chromatography.	2009 Oct	19653696
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
Molecular mechanisms of acquired resistance to tyrosine kinase targeted therapy.	2010 Apr 12	20385023
SRC: a century of science brought to the clinic.	2010 Aug	20689754
Novel dual Src/Abl inhibitors for hematologic and solid malignancies.	2010 Aug	20557276
Detection of centrosome aberrations in disease-unrelated cells from patients with tumor treated with tyrosine kinase inhibitors.	2010 Aug	20408871
Optimizing combination therapies with existing and future CML drugs.	2010 Aug 23	20808800
MASPECTRAS 2: An integration and analysis platform for proteomic data.	2010 Jul	20455215
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
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
Standard treatment of Ph+ CML in 2010: how, when and where not to use what BCR/ABL1 kinase inhibitor?	2010 Oct	20597967
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

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 `Mon Mar 31 22:41:58 GMT 2025` Edited by `admin` on `Mon Mar 31 22:41:58 GMT 2025`
Record UNII	EZM4KL4P89
Record Status	`Validated (UNII)`
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Name

Type

Language

Bosutinib methanoate

Common Name

English

3-Quinolinecarbonitrile, 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1-piperazinyl)propoxy]-, compd. with methanol (1:1)

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English

Code System Code Type Description

FDA UNII

EZM4KL4P89

Created by admin on Mon Mar 31 22:41:58 GMT 2025 , Edited by admin on Mon Mar 31 22:41:58 GMT 2025

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PUBCHEM

46780884

Created by admin on Mon Mar 31 22:41:58 GMT 2025 , Edited by admin on Mon Mar 31 22:41:58 GMT 2025

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CAS

918639-10-8

Created by admin on Mon Mar 31 22:41:58 GMT 2025 , Edited by admin on Mon Mar 31 22:41:58 GMT 2025

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EPA CompTox

DTXSID7049051

Created by admin on Mon Mar 31 22:41:58 GMT 2025 , Edited by admin on Mon Mar 31 22:41:58 GMT 2025

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					5018V4AEZ0

BOSUTINIB

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Patents

Sample Use Guides

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Drug as perpetrator