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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 of BOSUTINIB

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
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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 TargetPharmacologyConditionPotency
1.2 nM [IC50]
1.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
BOSULIF

Cmax

ValueDoseCo-administeredAnalytePopulation
273 ng/mL
500 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
190 ng/mL
400 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
76.6 ng/mL
300 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
95.4 ng/mL
200 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
19.6 ng/mL
100 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
6.9 ng/mL
50 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
4.89 ng/mL
50 mg single, oral
BOSUTINIB plasma
Homo sapiens
17 ng/mL
100 mg single, oral
BOSUTINIB plasma
Homo sapiens
43.1 ng/mL
200 mg single, oral
BOSUTINIB plasma
Homo sapiens
63.7 ng/mL
300 mg single, oral
BOSUTINIB plasma
Homo sapiens
117 ng/mL
400 mg single, oral
BOSUTINIB plasma
Homo sapiens
125 ng/mL
500 mg single, oral
BOSUTINIB plasma
Homo sapiens
206 ng/mL
600 mg single, oral
BOSUTINIB plasma
Homo sapiens
200 ng/mL
500 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
200 ng/mL
500 mg 1 times / day steady-state, oral
BOSUTINIB plasma
Homo sapiens
216 ng/mL
800 mg single, oral
BOSUTINIB plasma
Homo sapiens
125 ng/mL
500 mg single, oral
BOSUTINIB plasma
Homo sapiens
278.12 ng/mL
600 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
62.1 ng/mL
400 mg single, oral
BOSUTINIB plasma
Homo sapiens
88 ng/mL
400 mg single, oral
BOSUTINIB plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
3580 ng × h/mL
500 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
2900 ng × h/mL
400 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
1170 ng × h/mL
300 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
1670 ng × h/mL
200 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
329 ng × h/mL
100 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
114 ng × h/mL
50 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
129 ng × h/mL
50 mg single, oral
BOSUTINIB plasma
Homo sapiens
284 ng × h/mL
100 mg single, oral
BOSUTINIB plasma
Homo sapiens
920 ng × h/mL
200 mg single, oral
BOSUTINIB plasma
Homo sapiens
1200 ng × h/mL
300 mg single, oral
BOSUTINIB plasma
Homo sapiens
2340 ng × h/mL
400 mg single, oral
BOSUTINIB plasma
Homo sapiens
2950 ng × h/mL
500 mg single, oral
BOSUTINIB plasma
Homo sapiens
4300 ng × h/mL
600 mg single, oral
BOSUTINIB plasma
Homo sapiens
3650 ng × h/mL
500 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
3650 ng × h/mL
500 mg 1 times / day steady-state, oral
BOSUTINIB plasma
Homo sapiens
4000 ng × h/mL
800 mg single, oral
BOSUTINIB plasma
Homo sapiens
2950 ng × h/mL
500 mg single, oral
BOSUTINIB plasma
Homo sapiens
4084.7 ng × h/mL
600 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
1150 ng × h/mL
400 mg single, oral
BOSUTINIB plasma
Homo sapiens
1768 ng × h/mL
400 mg single, oral
BOSUTINIB plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
23.3 h
500 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
19.89 h
400 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
19.4 h
300 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
30 h
200 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
64.7 h
100 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
25.8 h
50 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
12.9 h
50 mg single, oral
BOSUTINIB plasma
Homo sapiens
18.6 h
100 mg single, oral
BOSUTINIB plasma
Homo sapiens
20.79 h
200 mg single, oral
BOSUTINIB plasma
Homo sapiens
17.1 h
300 mg single, oral
BOSUTINIB plasma
Homo sapiens
18.6 h
400 mg single, oral
BOSUTINIB plasma
Homo sapiens
21.9 h
500 mg single, oral
BOSUTINIB plasma
Homo sapiens
19.9 h
600 mg single, oral
BOSUTINIB plasma
Homo sapiens
22.5 h
500 mg 1 times / day steady-state, oral
BOSUTINIB plasma
Homo sapiens
33.8 h
800 mg single, oral
BOSUTINIB plasma
Homo sapiens
21.9 h
500 mg single, oral
BOSUTINIB plasma
Homo sapiens
15.4 h
600 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
39.1 h
400 mg single, oral
BOSUTINIB plasma
Homo sapiens
32.4 h
400 mg single, oral
BOSUTINIB plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
4%
500 mg 1 times / day multiple, oral
BOSUTINIB plasma
Homo sapiens
4%
500 mg 1 times / day steady-state, oral
BOSUTINIB plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

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
Record UNII
5018V4AEZ0
Record Status Validated (UNII)
Record Version