Bosutinib

Identification

Name

Bosutinib

Accession Number

DB06616

Description

Bosutinib is a Bcr-Abl kinase inhibitor for the treatment of Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML). Compared to other tyrosine kinase inhibitors, it has a more favourable hematologic toxicity profile. FDA approved on September 4, 2012.

Type

Small Molecule

Groups

Approved

Structure

Similar Structures

Weight: Average: 530.446
Monoisotopic: 529.164745233
Chemical Formula: C₂₆H₂₉Cl₂N₅O₃

Synonyms

4-((2,4-dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methyl-1-piperazinyl)propoxy)-3-quinolinecarbonitrile
Bosutinib

External IDs

SK-606
SKI 606
SKI-606

Pharmacology

Indication

Treatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy in adult patients.

Associated Conditions

Contraindications & Blackbox Warnings

Learn about our commercial Contraindications & Blackbox Warnings data.

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Pharmacodynamics

Not Available

Mechanism of action

Bosutinib is a tyrosine kinase inhibitor. Although it is able to inhibit several tyrosine kinases such as Src, Lyn, and Hck, which are members of the Src-family of kinases, its primary target is the Bcr-Abl kinase. The Bcr-Abl gene is a chimeric oncogene created from the fusion of the breakpoint-cluster (Bcr) gene and Abelson (Abl) tyrosine gene. This chromosomal abnormality results in the formation of what is commonly known as the Philadelphia chromosome or Philadelphia translocation. The Bcr-Abl gene expresses a particular kinase that promotes the progression of CML. A decrease in the growth and size of the CML tumour has been observed following administration of bosutinib. Bosutinib did not inhibit the T315I and V299L mutant cells.

Target	Actions	Organism
ABreakpoint cluster region protein	inhibitor	Humans
ATyrosine-protein kinase ABL1	inhibitor	Humans
UTyrosine-protein kinase Lyn	Not Available	Humans
UTyrosine-protein kinase HCK	inhibitor	Humans
UProto-oncogene tyrosine-protein kinase Src	inhibitor	Humans
UCyclin-dependent kinase 2	inhibitor	Humans
UDual specificity mitogen-activated protein kinase kinase 1	inhibitor	Humans
UDual specificity mitogen-activated protein kinase kinase 2	inhibitor	Humans
UMitogen-activated protein kinase kinase kinase 2	inhibitor	Humans
UCalcium/calmodulin-dependent protein kinase type II subunit gamma	inhibitor	Humans

Absorption

Food increase the exposure of bosutinib. Tmax, single dose, cancer patients, fed-state = 4-6 hours; After 15 daily doses of bosutinib 500 mg with food in CML patients, the pharmacokinetic parameters are as follows: Cmax = 200 ng/mL; AUC = 3650 ng∙h/mL

Volume of distribution

Apparent volume of distribution = 6080 ± 1230 L.

Protein binding

94% bound to human plasma proteins in vitro. 96% bound to human plasma proteins in healthy subjects ex vivo. Extent of protein binding is not concentration-dependent.

Metabolism

Bosutinib is primarily metabolized by CYP3A4. The major circulating metabolites identified in plasma are oxydechlorinated (M2) bosutinib (19% of parent exposure) and N-desmethylated (M5) bosutinib (25% of parent exposure), with bosutinib N-oxide (M6) as a minor circulating metabolite. All the metabolites were deemed inactive.

Route of elimination

When given a single oral dose, 91.3% of the dose was recovered in feces and 3% of the dose recovered in urine.

Half-life

Terminal phase elimination half-life, single oral dose, fed-state = 22.5 hours

Clearance

Mean clearance (CL/F), single oral dose, fed-state = 189 L/h

Adverse Effects

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Toxicity

Most common adverse reactions (incidence greater than 20%) are diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, and fatigue. Because bosutinib is not an inhibitor of c-KIT or PDGF receptor, it has less hematologic toxicities.

Affected organisms

Humans and other mammals

Pathways

Pathway	Category
Bosutinib Inhibition of BCR-ABL	Drug action

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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Abaloparatide	The therapeutic efficacy of Abaloparatide can be decreased when used in combination with Bosutinib.
Abametapir	The serum concentration of Bosutinib can be increased when it is combined with Abametapir.
Abatacept	The metabolism of Bosutinib can be increased when combined with Abatacept.
Abciximab	The risk or severity of bleeding can be increased when Abciximab is combined with Bosutinib.
Abemaciclib	The metabolism of Abemaciclib can be decreased when combined with Bosutinib.
Abiraterone	The metabolism of Bosutinib can be decreased when combined with Abiraterone.
Acalabrutinib	The metabolism of Acalabrutinib can be decreased when combined with Bosutinib.
Acenocoumarol	The serum concentration of Acenocoumarol can be increased when it is combined with Bosutinib.
Acetaminophen	The metabolism of Acetaminophen can be increased when combined with Bosutinib.
Acetazolamide	The metabolism of Bosutinib can be decreased when combined with Acetazolamide.

Additional Data Available

Extended Description

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Extended description of the mechanism of action and particular properties of each drug interaction.

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Severity

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A severity rating for each drug interaction, from minor to major.

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Evidence Level

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A rating for the strength of the evidence supporting each drug interaction.

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Action

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An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions

Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of bosutinib.
Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of bosutinib.
Take with food. Coadministration with a high-fat meal may increase the AUC of bosutinib.

Products

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Bosutinib monohydrate	844ZJE6I55	918639-08-4	BXPOSPOKHGNMEP-UHFFFAOYSA-N

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Unlock Additional Data
Bosulif	Tablet, film coated		Oral	Pfizer Europe Ma Eeig	2013-03-27	Not applicable
Bosulif	Tablet, film coated	100 mg/1	Oral	Pfizer Laboratories Div Pfizer Inc	2012-09-04	Not applicable
Bosulif	Tablet, film coated	500 mg	Oral	Pfizer Europe Ma Eeig	2013-03-26	Not applicable
Bosulif	Tablet	100 mg	Oral	Pfizer Canada Ulc	2014-04-24	Not applicable
Bosulif	Tablet, film coated	100 mg	Oral	Pfizer Europe Ma Eeig	2013-03-26	Not applicable
Bosulif	Tablet, film coated	400 mg/1	Oral	Pfizer Laboratories Div Pfizer Inc	2017-12-18	Not applicable
Bosulif	Tablet, film coated	100 mg/1	Oral	U.S. Pharmaceuticals	2012-09-04	Not applicable
Bosulif	Tablet, film coated	500 mg	Oral	Pfizer Europe Ma Eeig	2013-03-26	Not applicable
Bosulif	Tablet	400 mg	Oral	Pfizer Canada Ulc	Not applicable	Not applicable
Bosulif	Tablet, film coated		Oral	Pfizer Europe Ma Eeig	2013-03-27	Not applicable

Additional Data Available

Application Number

Available for Purchase

A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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Product Code

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A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Chemical Identifiers

UNII: 5018V4AEZ0
CAS number: 380843-75-4
InChI Key: UBPYILGKFZZVDX-UHFFFAOYSA-N
InChI: 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)
IUPAC Name: 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile
SMILES: COC1=CC(NC2=C(C=NC3=CC(OCCCN4CCN(C)CC4)=C(OC)C=C23)C#N)=C(Cl)C=C1Cl

References

General References

Amsberg GK, Schafhausen P: Bosutinib in the management of chronic myelogenous leukemia. Biologics. 2013;7:115-22. doi: 10.2147/BTT.S30182. Epub 2013 May 6. [PubMed:23674887]
Keller-V Amsberg G, Brummendorf TH: Novel aspects of therapy with the dual Src and Abl kinase inhibitor bosutinib in chronic myeloid leukemia. Expert Rev Anticancer Ther. 2012 Sep;12(9):1121-7. doi: 10.1586/era.12.84. [PubMed:23098112]

External Links

Human Metabolome Database: HMDB0240205
KEGG Drug: D03252
PubChem Compound: 5328940
PubChem Substance: 175427079
ChemSpider: 4486102
BindingDB: 4552
RxNav: 1307619
ChEBI: 39112
ChEMBL: CHEMBL288441
ZINC: ZINC000022448983
PDBe Ligand: DB8
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Bosutinib

AHFS Codes

10:00.00 — Antineoplastic Agents

PDB Entries

3soa / 3ue4 / 4mxo / 4mxx / 4mxy / 4mxz / 4qmn / 5ajq / 5i9x / 5vc3 …

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FDA label

Download (326 KB)

MSDS

Download (97.1 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Completed	Treatment	Previously Treated PH + CML	1
3	Active Not Recruiting	Treatment	Chronic Chronic myelogenous leukemia	1
3	Completed	Treatment	Chronic Myeloid Leukemia (CML)	1
3	Completed	Treatment	Leukemia, Myelogenous, Chronic, Breakpoint Cluster Region-Abelson Proto-oncogene (BCR-ABL) Positive	1
2	Active Not Recruiting	Treatment	BCR-ABL Positive Chronic Myelogenous Leukemia / Chronic Myeloid Leukemia (CML) / Chronic Myeloid Leukemia in Remission	1
2	Active Not Recruiting	Treatment	Chronic Chronic myelogenous leukemia	1
2	Completed	Treatment	Autosomal Dominant Polycystic Kidney Disease （ADPKD)	1
2	Completed	Treatment	BCR-ABL Positive / Chronic / Leukemias / Myelogenous	1
2	Completed	Treatment	Chronic Chronic myelogenous leukemia	1
2	Completed	Treatment	Chronic Myeloblastic Leukaemia	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Tablet	Oral	100 mg
Tablet	Oral	400 mg
Tablet	Oral	500 mg
Tablet, film coated	Oral
Tablet, film coated	Oral	100 mg
Tablet, film coated	Oral	100 mg/1
Tablet, film coated	Oral	400 mg/1
Tablet, film coated	Oral	500 mg
Tablet, film coated	Oral	500 mg/1
Tablet, coated	Oral	100 mg
Tablet, coated	Oral	500 mg

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
Unlock Additional Data
US6002008	No	1999-12-14	2018-03-27
US7417148	No	2008-08-26	2026-01-23
USRE42376	No	2011-05-17	2019-09-24
US7767678	No	2010-08-03	2026-11-23
US7919625	No	2011-04-05	2025-12-11

Additional Data Available

Filed On

Available for Purchase

The date on which a patent was filed with the relevant government.

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Properties

State

Solid

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.0095 mg/mL	ALOGPS
logP	4.87	ALOGPS
logP	4.09	ChemAxon
logS	-4.8	ALOGPS
pKa (Strongest Acidic)	15.48	ChemAxon
pKa (Strongest Basic)	8.43	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	8	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	82.88 Å²	ChemAxon
Rotatable Bond Count	9	ChemAxon
Refractivity	142.12 m³·mol^-1	ChemAxon
Polarizability	56.14 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.9823
Blood Brain Barrier	+	0.9272
Caco-2 permeable	+	0.6542
P-glycoprotein substrate	Substrate	0.7601
P-glycoprotein inhibitor I	Inhibitor	0.8409
P-glycoprotein inhibitor II	Inhibitor	0.9108
Renal organic cation transporter	Inhibitor	0.5663
CYP450 2C9 substrate	Non-substrate	0.854
CYP450 2D6 substrate	Non-substrate	0.6953
CYP450 3A4 substrate	Substrate	0.6987
CYP450 1A2 substrate	Inhibitor	0.5606
CYP450 2C9 inhibitor	Non-inhibitor	0.7372
CYP450 2D6 inhibitor	Non-inhibitor	0.5136
CYP450 2C19 inhibitor	Non-inhibitor	0.5725
CYP450 3A4 inhibitor	Inhibitor	0.5
CYP450 inhibitory promiscuity	High CYP Inhibitory Promiscuity	0.7021
Ames test	AMES toxic	0.5922
Carcinogenicity	Non-carcinogens	0.8869
Biodegradation	Not ready biodegradable	1.0
Rat acute toxicity	2.4201 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Strong inhibitor	0.6147
hERG inhibition (predictor II)	Inhibitor	0.7754

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
MS/MS Spectrum - , positive	LC-MS/MS	splash10-014i-0092000000-68183c460c3cf8e08c01
MS/MS Spectrum - , positive	LC-MS/MS	splash10-001l-1900080000-86f44693fc4098040447

Targets

Details1. Breakpoint cluster region protein

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Rho guanyl-nucleotide exchange factor activity
Specific Function: GTPase-activating protein for RAC1 and CDC42. Promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. Displays serine/threonine kinase activity.
Gene Name: BCR
Uniprot ID: P11274
Uniprot Name: Breakpoint cluster region protein
Molecular Weight: 142818.07 Da

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	0.5	N/A	N/A	19039322
IC 50 (nM)	1.1	N/A	N/A	16220969 / 20166671
IC 50 (nM)	20	N/A	N/A	16970400
Kd (nM)	0.029	N/A	N/A	22037378
Kd (nM)	0.036	N/A	N/A	22037378
Kd (nM)	0.037	N/A	N/A	22037378
Kd (nM)	0.039	N/A	N/A	22037378
Kd (nM)	0.047	N/A	N/A	22037378
Kd (nM)	0.057	N/A	N/A	22037378
Kd (nM)	0.062	N/A	N/A	22037378
Kd (nM)	0.086	N/A	N/A	22037378
Kd (nM)	0.11	N/A	N/A	22037378
Kd (nM)	0.12	N/A	N/A	22037378
Kd (nM)	0.18	N/A	N/A	22037378
Kd (nM)	0.63	N/A	N/A	22037378
Kd (nM)	21	N/A	N/A	22037378
Kd (nM)	3.6	N/A	N/A	22037378

Details2. Tyrosine-protein kinase ABL1

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Syntaxin binding
Specific Function: Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility a...
Gene Name: ABL1
Uniprot ID: P00519
Uniprot Name: Tyrosine-protein kinase ABL1
Molecular Weight: 122871.435 Da

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	8	N/A	N/A	19039322
Kd (nM)	4.2	N/A	N/A	22037378

Details3. Tyrosine-protein kinase Lyn

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Receptor signaling protein tyrosine kinase activity
Specific Function: Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, respons...
Gene Name: LYN
Uniprot ID: P07948
Uniprot Name: Tyrosine-protein kinase Lyn
Molecular Weight: 58573.595 Da

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	3.2	N/A	N/A	19039322
Kd (nM)	3.4	N/A	N/A	22037378

Details4. Tyrosine-protein kinase HCK

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Receptor binding
Specific Function: Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, includ...
Gene Name: HCK
Uniprot ID: P08631
Uniprot Name: Tyrosine-protein kinase HCK
Molecular Weight: 59599.355 Da

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	1	N/A	N/A	19039322 / 21459579
IC 50 (nM)	1.2	N/A	N/A	12941315 / 18485715 / 18930653 / 19321350
IC 50 (nM)	1.2	7.5	30	11689083 / 14552782 / 16161995
IC 50 (nM)	1.8	N/A	N/A	18930653
IC 50 (nM)	100	N/A	N/A	12941315 / 19632113 / 20363128
IC 50 (nM)	3.6	7.5	37	15745832
IC 50 (nM)	3.8	N/A	N/A	16220969 / 19632113 / 20166671 / 20363128
IC 50 (nM)	3.8	7.5	37	15615514 / 15916442 / 17181170
Kd (nM)	1	N/A	N/A	22037378

Details5. Proto-oncogene tyrosine-protein kinase Src

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Sh3/sh2 adaptor activity
Specific Function: Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion recept...
Gene Name: SRC
Uniprot ID: P12931
Uniprot Name: Proto-oncogene tyrosine-protein kinase Src
Molecular Weight: 59834.295 Da

Property	Measurement	pH	Temperature (°C)	References
Kd (nM)	>10000	N/A	N/A	22037378

Details6. Cyclin-dependent kinase 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Metal ion binding
Specific Function: Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, N...
Gene Name: CDK2
Uniprot ID: P24941
Uniprot Name: Cyclin-dependent kinase 2
Molecular Weight: 33929.215 Da

References

Remsing Rix LL, Rix U, Colinge J, Hantschel O, Bennett KL, Stranzl T, Muller A, Baumgartner C, Valent P, Augustin M, Till JH, Superti-Furga G: Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells. Leukemia. 2009 Mar;23(3):477-85. doi: 10.1038/leu.2008.334. Epub 2008 Nov 27. [PubMed:19039322]

Property	Measurement	pH	Temperature (°C)	References
Kd (nM)	19	N/A	N/A	22037378

Details7. Dual specificity mitogen-activated protein kinase kinase 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Receptor signaling protein tyrosine phosphatase activity
Specific Function: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones t...
Gene Name: MAP2K1
Uniprot ID: Q02750
Uniprot Name: Dual specificity mitogen-activated protein kinase kinase 1
Molecular Weight: 43438.65 Da

References

Remsing Rix LL, Rix U, Colinge J, Hantschel O, Bennett KL, Stranzl T, Muller A, Baumgartner C, Valent P, Augustin M, Till JH, Superti-Furga G: Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells. Leukemia. 2009 Mar;23(3):477-85. doi: 10.1038/leu.2008.334. Epub 2008 Nov 27. [PubMed:19039322]

Property	Measurement	pH	Temperature (°C)	References
Kd (nM)	9.9	N/A	N/A	22037378

Details8. Dual specificity mitogen-activated protein kinase kinase 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Scaffold protein binding
Specific Function: Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity).
Gene Name: MAP2K2
Uniprot ID: P36507
Uniprot Name: Dual specificity mitogen-activated protein kinase kinase 2
Molecular Weight: 44423.735 Da

References

Remsing Rix LL, Rix U, Colinge J, Hantschel O, Bennett KL, Stranzl T, Muller A, Baumgartner C, Valent P, Augustin M, Till JH, Superti-Furga G: Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells. Leukemia. 2009 Mar;23(3):477-85. doi: 10.1038/leu.2008.334. Epub 2008 Nov 27. [PubMed:19039322]

Property	Measurement	pH	Temperature (°C)	References
Kd (nM)	30	N/A	N/A	22037378

Details9. Mitogen-activated protein kinase kinase kinase 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Protein serine/threonine kinase activity
Specific Function: Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7 (By similarity). Plays a role in caveolae kiss-and...
Gene Name: MAP3K2
Uniprot ID: Q9Y2U5
Uniprot Name: Mitogen-activated protein kinase kinase kinase 2
Molecular Weight: 69740.21 Da

References

Ahmad S, Hughes MA, Johnson GL, Scott JE: Development and validation of a high-throughput intrinsic ATPase activity assay for the discovery of MEKK2 inhibitors. J Biomol Screen. 2013 Apr;18(4):388-99. doi: 10.1177/1087057112466430. Epub 2012 Nov 7. [PubMed:23134735]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	184	N/A	N/A	19039322
Kd (nM)	3600	N/A	N/A	22037378

Details10. Calcium/calmodulin-dependent protein kinase type II subunit gamma

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Protein homodimerization activity
Specific Function: Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in sarcoplsamic reticulum Ca(2+) transport in skelet...
Gene Name: CAMK2G
Uniprot ID: Q13555
Uniprot Name: Calcium/calmodulin-dependent protein kinase type II subunit gamma
Molecular Weight: 62608.655 Da

References

Amsberg GK, Koschmieder S: Profile of bosutinib and its clinical potential in the treatment of chronic myeloid leukemia. Onco Targets Ther. 2013;6:99-106. doi: 10.2147/OTT.S19901. Epub 2013 Mar 4. [PubMed:23493838]

Enzymes

Details1. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate
Inhibitor

General Function: Vitamin d3 25-hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name: CYP3A4
Uniprot ID: P08684
Uniprot Name: Cytochrome P450 3A4
Molecular Weight: 57342.67 Da

References

Filppula AM, Neuvonen PJ, Backman JT: In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug Metab Dispos. 2014 Jul;42(7):1202-9. doi: 10.1124/dmd.114.057695. Epub 2014 Apr 8. [PubMed:24713129]

Details2. Cytochrome P450 2C8

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Steroid hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP2C8
Uniprot ID: P10632
Uniprot Name: Cytochrome P450 2C8
Molecular Weight: 55824.275 Da

References

Filppula AM, Neuvonen PJ, Backman JT: In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug Metab Dispos. 2014 Jul;42(7):1202-9. doi: 10.1124/dmd.114.057695. Epub 2014 Apr 8. [PubMed:24713129]

Transporters

Details1. P-glycoprotein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Xenobiotic-transporting atpase activity
Specific Function: Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name: ABCB1
Uniprot ID: P08183
Uniprot Name: Multidrug resistance protein 1
Molecular Weight: 141477.255 Da

Drug created on March 19, 2008 10:41 / Updated on January 25, 2021 22:38

Bosutinib

Identification

Structure for Bosutinib (DB06616)

Pharmacology

Learn about our commercial Contraindications & Blackbox Warnings data.

Learn about our commercial Adverse Effects data.

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Targets

References

References

References

References

References

Enzymes

References

References

Transporters