Identification
- Summary
Bosutinib is an antineoplastic agent used for the treatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) in adults with inadequate clinical response to other treatments.
- Brand Names
- Bosulif
- Generic Name
- Bosutinib
- DrugBank Accession Number
- DB06616
- Background
Bosutinib is a 7-alkoxy-3-quinolinecarbonitrile that functions as a potent, dual SRC and ABL tyrosine kinase inhibitor indicated for chronic myelogenous leukemia (CML), specifically Philadelphia chromosome-positive (Ph+) CML. Philadelphia chromosome is a hallmark of CML due to the reciprocal translocation t(9;22)(q34;q11), resulting in a BCR-ABL fusion protein.2,3,5 The first BCR-ABL inhibitor, imatinib, was introduced over a decade ago as a breakthrough in CML management; however, emerging resistance to imatinib poses challenges in achieving remission.4 Second-generation BCR-ABL inhibitors like bosutinib inhibit most resistance-conferring BCR-ABL mutations except V299L and T315, thus providing more therapeutic options for patients.1,4
Bosutinib was first approved by the FDA in 2012 for the treatment of adult chronic, accelerated, or blast-phase Ph+ CML with resistance or intolerance to prior therapy.10 On September 26, 2023, bosutinib was also approved by the FDA for the treatment of pediatric CML that is newly diagnosed or resistant/intolerant to prior therapy. This approval was based on favorable results obtained from the open-label, randomized, multicenter trial BFORE that showed a significant improvement in major molecular response, defined as a ≤0.1% BCR ABL ratio on an international scale, with bosutinib treatment.11
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Bosutinib (DB06616)
- 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
Bosutinib is indicated for the treatment of adult and pediatric patients 1 year of age and older with chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia that is newly diagnosed or resistant or intolerant to prior therapy. It is also indicated for the treatment of adult patients with accelerated or blast phase Philadelphia chromosome-positive chronic myelogenous leukemia that is newly diagnosed or resistant or intolerant to prior therapy.6
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Accelerated phase chronic myelogenous leukemia (cml) •••••••••••• ••••• •••••••••• •• ••••••••••• •• ••••• ••••••• •••••••• •••••• Treatment of Chronic phase chronic myeloid leukemia •••••••••••• •••••• ••••••••• ••••• ••••••••• •••••••• •••••• Treatment of Chronic phase chronic myeloid leukemia •••••••••••• •••••• ••••••••• •••••••••• •• ••••••••••• •• ••••• ••••••• •••••••• •••••• Treatment of Blast phase chronic myelocytic leukemia •••••••••••• ••••• •••••••••• •• ••••••••••• •• ••••• ••••••• •••••••• •••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
A greater likelihood of response and a greater likelihood of safety events were observed with higher bosutinib exposure in clinical studies. The time course of bosutinib pharmacodynamic response has not been fully characterized.6
At a single oral dose of 500 mg bosutinib with ketoconazole (a strong CYP3A inhibitor), bosutinib does not prolong the QT interval to any clinically relevant extent.6
- Mechanism of action
Bosutinib is a tyrosine kinase inhibitor. Bosutinib inhibits the BCR-ABL kinase that promotes CML; it is also an inhibitor of Src-family kinases including Src, Lyn, and Hck. Bosutinib inhibited 16 of 18 imatinib-resistant forms of BCR-ABL kinase expressed in murine myeloid cell lines. Bosutinib did not inhibit the T315I and V299L mutant cells.6
Target Actions Organism ATyrosine-protein kinase ABL1 inhibitorHumans ATyrosine-protein kinase Lyn inhibitorHumans AProto-oncogene tyrosine-protein kinase Src inhibitorHumans ADual specificity mitogen-activated protein kinase kinase 1 inhibitorHumans ADual specificity mitogen-activated protein kinase kinase 2 inhibitorHumans AMitogen-activated protein kinase kinase kinase 2 inhibitorHumans ACalcium/calmodulin-dependent protein kinase type II subunit gamma inhibitorHumans ATyrosine-protein kinase Fgr inhibitorHumans ATyrosine-protein kinase HCK inhibitorHumans ATyrosine-protein kinase Tec inhibitorHumans ASTE20-like serine/threonine-protein kinase inhibitorHumans - Absorption
Bosutinib exhibits dose-proportional increases in Cmax and AUC over the oral dose range of 200 to 800 mg (0.33 to 1.3 times the maximum approved recommended dosage of 600 mg). Bosutinib steady-state Cmax was 127 ng/mL (31%), Ctrough was 68 ng/mL (39%) and AUC was 2370 ng•h/mL (34%) following multiple oral doses of bosutinib 400 mg. Bosutinib steady-state Cmax was 171 ng/mL (38%), Ctrough was 91 ng/mL (42%) and AUC was 3150 ng•h/mL (38%) following multiple oral doses of bosutinib 500 mg. No clinically significant differences in the pharmacokinetics of bosutinib were observed following administration of either the tablet or capsule dosage forms of bosutinib at the same dose, under fed conditions.6
The median bosutinib (minimum, maximum) tmax was 6.0 (6.0, 6.0) hours following oral administration of a single oral dose of bosutinib 500 mg with food. The absolute bioavailability was 34% in healthy subjects.6
Bosutinib Cmax increased 1.8-fold and AUC increased 1.7-fold when bosutinib tablets were given with a high-fat meal to healthy subjects compared to administration under fasted conditions. Bosutinib Cmax increased 1.6-fold and AUC increased 1.5-fold when bosutinib capsules were given with a high-fat meal to healthy subjects compared to administration under fasted conditions. The high-fat meal (800-1000 total calories) consisted of approximately 150 protein calories, 250 carbohydrate calories, and 500-600 fat calories.6
- Volume of distribution
The mean (SD) apparent bosutinib volume of distribution is 6080 ± 1230 L after an oral dose of 500 mg of bosutinib.6
- Protein binding
Bosutinib protein binding is 94% in vitro and 96% ex vivo and is independent of concentration.6
- 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.
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- Route of elimination
Following a single oral dose of [14C] radiolabeled bosutinib without food, 91.3% of the dose was recovered in feces and 3.3% of the dose was recovered in urine.6
- Half-life
The mean (SD) bosutinib terminal phase elimination half-life (t1/2) was 22.5 ± 1.7 hours following a single oral dose of bosutinib.6
- Clearance
The mean (SD) apparent clearance was 189 ± 48 L/h following a single oral dose of bosutinib.6
- Adverse Effects
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In a rat fertility and early embryonic development study, bosutinib was administered orally to female rats for approximately 3 to 6 weeks, depending on the day of mating (2 weeks prior to cohabitation with untreated breeder males until gestation day [GD] 7). Increased embryonic resorptions occurred at greater than or equal to 10 mg/kg/day of bosutinib (1.6 and 1.2 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively), and decreased implantations and reduced number of viable embryos at 30 mg/kg/day of bosutinib (3.4 and 2.5 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively).6
In an embryo-fetal development study conducted in rabbits, bosutinib was administered orally to pregnant animals during organogenesis at doses of 3, 10, and 30 mg/kg/day. At the maternally-toxic dose of 30 mg/kg/day of bosutinib, there were fetal anomalies (fused sternebrae and 2 fetuses had various visceral observations), and an approximate 6% decrease in fetal body weight. The dose of 30 mg/kg/day resulted in exposures (AUC) approximately 5.1 and 3.8 times the human exposures at the recommended doses of 400 and 500 mg/day, respectively.6
Fetal exposure to bosutinib-derived radioactivity during pregnancy was demonstrated in a placental-transfer study in pregnant rats. In a rat pre-and postnatal development study, bosutinib was administered orally to pregnant animals during the period of organogenesis through lactation day 20 at doses of 10, 30, and 70 mg/kg/day. Reduced number of pups born occurred at greater than or equal to 30 mg/kg/day bosutinib (3.4 and 2.5 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively), and increased incidence of total litter loss and decreased growth of offspring after birth occurred at 70 mg/kg/day bosutinib (6.9 and 5.1 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively).6
Experience with bosutinib overdose in clinical studies was limited to isolated cases. There were no reports of any serious adverse events associated with the overdoses. Patients who take an overdose of BOSULIF should be observed and given appropriate supportive treatment.6
Bosutinib was not carcinogenic in rats or transgenic mice. The rat 2-year carcinogenicity study was conducted at bosutinib oral doses up to 25 mg/kg in males and 15 mg/kg in females. Exposures at these doses were approximately 1.5 times (males) and 3.1 times (females) the human exposure at the 400 mg dose and 1.2 times (males) and 2.4 times (females) exposure in humans at the 500 mg dose. The 6-month RasH2 transgenic mouse carcinogenicity study was conducted at bosutinib oral doses up to 60 mg/kg.6
Bosutinib was not mutagenic or clastogenic in a battery of tests, including the bacteria reverse mutation assay (Ames Test), the in vitro assay using human peripheral blood lymphocytes and the micronucleus test in orally treated male mice.6
In a rat fertility study, drug-treated males were mated with untreated females or untreated males were mated with drug-treated females. Females were administered the drug from pre-mating through early embryonic development. The dose of 70 mg/kg/day of bosutinib resulted in reduced fertility in males as demonstrated by 16% reduction in the number of pregnancies. There were no lesions in the male reproductive organs at this dose. This dose of 70 mg/kg/day resulted in exposure (AUC) in male rats approximately 1.5 times and equal to human exposure at the recommended doses of 400 and 500 mg/day, respectively. Fertility (number of pregnancies) was not affected when female rats were treated with bosutinib. However, there were increased embryonic resorptions at greater than or equal to 10 mg/kg/day of bosutinib (1.6 and 1.2 times the human exposure at the recommended doses of 400 and 500 mg/day, respectively), and decreased implantations and reduced number of viable embryos at 30 mg/kg/day of bosutinib (3.4 and 2.5 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively).6
- Pathways
Pathway Category Bosutinib Inhibition of BCR-ABL Drug action - Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 Integrate drug-drug
interactions in your softwareAbametapir 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. Abrocitinib The serum concentration of Bosutinib can be increased when it is combined with Abrocitinib. - 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
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- 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 Region Image Bosulif Tablet, film coated 500 mg Oral Pfizer Europe Ma Eeig 2016-09-08 Not applicable EU 
Bosulif Capsule 100 mg/1 Oral Pfizer Laboratories Div Pfizer Inc 2024-01-02 Not applicable US 
Bosulif Tablet 400 mg Oral Pfizer Canada Ulc Not applicable Not applicable Canada 
Bosulif Tablet, film coated 400 mg/1 Oral Pfizer Laboratories Div Pfizer Inc 2017-12-18 Not applicable US Bosulif Tablet, film coated 100 mg Oral Pfizer Europe Ma Eeig 2016-09-08 Not applicable EU
Categories
- ATC Codes
- L01EA04 — Bosutinib
- Drug Categories
- Amines
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Bcr-Abl Tyrosine Kinase Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C8 Inhibitors (weak)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Enzyme Inhibitors
- Heterocyclic Compounds, Fused-Ring
- Immunosuppressive Agents
- Kinase Inhibitor
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Protein Kinase Inhibitors
- Tyrosine Kinase Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as 4-aminoquinolines. These are organic compounds containing an amino group attached to the 4-position of a quinoline ring system.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Quinolines and derivatives
- Sub Class
- Aminoquinolines and derivatives
- Direct Parent
- 4-aminoquinolines
- Alternative Parents
- Aminophenyl ethers / Methoxyanilines / Phenoxy compounds / Anisoles / Dichlorobenzenes / Methoxybenzenes / Alkyl aryl ethers / Aminopyridines and derivatives / N-methylpiperazines / Aryl chlorides show 8 more
- Substituents
- 1,3-dichlorobenzene / 1,4-diazinane / 4-aminoquinoline / Alkyl aryl ether / Amine / Aminophenyl ether / Aminopyridine / Aniline or substituted anilines / Anisole / Aromatic heteropolycyclic compound show 30 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- tertiary amino compound, aromatic ether, nitrile, dichlorobenzene, aminoquinoline, N-methylpiperazine (CHEBI:39112)
- Affected organisms
- Humans and other mammals
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
- Synthesis Reference
http://www.ncbi.nlm.nih.gov/pubmed/23674887
- 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. [Article]
- 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. [Article]
- Drexler HG, MacLeod RA, Uphoff CC: Leukemia cell lines: in vitro models for the study of Philadelphia chromosome-positive leukemia. Leuk Res. 1999 Mar;23(3):207-15. doi: 10.1016/s0145-2126(98)00171-4. [Article]
- 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. [Article]
- Keller G, Schafhausen P, Brummendorf TH: Bosutinib. Recent Results Cancer Res. 2010;184:119-27. doi: 10.1007/978-3-642-01222-8_9. [Article]
- FDA Approved Drug Products: BOSULIF® (bosutinib) tablets/capsules, for oral use (October 2023) [Link]
- FDA Approved Drug Products: BOSULIF (bosutinib) tablets, for oral use [Link]
- Bosutinib Pfizer MSDS [Link]
- Bosutinib Thermofisher Scientific MSDS [Link]
- FDA grants accelerated approval to bosutinib for treatment of newly-diagnosed PH+ CML [Link]
- FDA approves bosutinib for pediatric patients with chronic myelogenous leukemia [Link]
- External Links
- Human Metabolome Database
- HMDB0240205
- KEGG Drug
- D03252
- PubChem Compound
- 5328940
- PubChem Substance
- 175427079
- ChemSpider
- 4486102
- BindingDB
- 4552
- 1307619
- ChEBI
- 39112
- ChEMBL
- CHEMBL288441
- ZINC
- ZINC000022448983
- PDBe Ligand
- DB8
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Bosutinib
- PDB Entries
- 3soa / 3ue4 / 4mxo / 4mxx / 4mxy / 4mxz / 4qmn / 5ajq / 5i9x / 5vc3 … show 3 more
- FDA label
- Download (326 KB)
- MSDS
- Download (97.1 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Recruiting Treatment Chronic Myelogenous Leukemia (CML) / Philadelphia Chromosome Positive (Ph+) Chronic Myeloid Leukemia (CML) 1 4 Terminated Treatment Previously Treated PH + CML 1 3 Active Not Recruiting Treatment Chronic Myelogenous Leukemia (CML) 1 3 Active Not Recruiting Treatment Philadelphia Chromosome Positive (Ph+) Chronic Myeloid Leukemia (CML) 1 3 Completed Treatment Chronic Myelogenous Leukemia (CML) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 100 mg/1 Capsule Oral 50 mg/1 Tablet Oral 100 mg Tablet Oral 400 mg Tablet Oral 500 mg Tablet, film coated Oral 100 mg/1 Tablet, film coated Oral 100 MG Tablet, film coated Oral 400 MG Tablet, film coated Oral 400 mg/1 Tablet, film coated Oral 500 MG Tablet, film coated Oral 500 mg/1 Tablet, coated Oral 50000000 mg Tablet, coated Oral 100 mg Tablet, coated Oral 500 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6002008 No 1999-12-14 2018-03-27 US US7417148 Yes 2008-08-26 2026-06-11 US USRE42376 Yes 2011-05-17 2024-10-13 US US7767678 Yes 2010-08-03 2027-05-23 US US7919625 Yes 2011-04-05 2026-06-11 US US11103497 Yes 2021-08-31 2034-08-28 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 131 - 134 °C Thermofisher MSDS label logP 3.34 Pfizer MSDS label - 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) 8.03 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 56.02 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 235.5973979 predictedDarkChem Lite v0.1.0 [M-H]- 213.89542 predictedDeepCCS 1.0 (2019) [M+H]+ 236.7142979 predictedDarkChem Lite v0.1.0 [M+H]+ 216.25343 predictedDeepCCS 1.0 (2019) [M+Na]+ 236.8075979 predictedDarkChem Lite v0.1.0 [M+Na]+ 223.04863 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- Inhibits both endogenous ABL and BCR-ABL fusion protein
- 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
References
- FDA Approved Drug Products: BOSULIF® (bosutinib) tablets/capsules, for oral use (October 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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
References
- Berndt S, Gurevich VV, Iverson TM: Crystal structure of the SH3 domain of human Lyn non-receptor tyrosine kinase. PLoS One. 2019 Apr 10;14(4):e0215140. doi: 10.1371/journal.pone.0215140. eCollection 2019. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- 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
References
- FDA Approved Drug Products: BOSULIF® (bosutinib) tablets/capsules, for oral use (October 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Protein tyrosine kinase activity
- Specific Function
- Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocy...
- Gene Name
- FGR
- Uniprot ID
- P09769
- Uniprot Name
- Tyrosine-protein kinase Fgr
- Molecular Weight
- 59478.11 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- 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
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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Non-receptor tyrosine kinase that contributes to signaling from many receptors and participates as a signal transducer in multiple downstream pathways, including regulation of the actin cytoskeleton. Plays a redundant role to ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. Required for TCR-dependent IL2 gene induction. Phosphorylates DOK1, one CD28-specific substrate, and contributes to CD28-signaling. Mediates signals that negatively regulate IL2RA expression induced by TCR cross-linking. Plays a redundant role to BTK in BCR-signaling for B-cell development and activation, especially by phosphorylating STAP1, a BCR-signaling protein. Required in mast cells for efficient cytokine production. Involved in both growth and differentiation mechanisms of myeloid cells through activation by the granulocyte colony-stimulating factor CSF3, a critical cytokine to promoting the growth, differentiation, and functional activation of myeloid cells. Participates in platelet signaling downstream of integrin activation. Cooperates with JAK2 through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. GRB10, a negative modifier of the FOS activation pathway, is another substrate of TEC. TEC is involved in G protein-coupled receptor- and integrin-mediated signalings in blood platelets. Plays a role in hepatocyte proliferation and liver regeneration and is involved in HGF-induced ERK signaling pathway. TEC regulates also FGF2 unconventional secretion (endoplasmic reticulum (ER)/Golgi-independent mechanism) under various physiological conditions through phosphorylation of FGF2 'Tyr-215'. May also be involved in the regulation of osteoclast differentiation.
- Specific Function
- Atp binding
- Gene Name
- TEC
- Uniprot ID
- P42680
- Uniprot Name
- Tyrosine-protein kinase Tec
- Molecular Weight
- 73580.73 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Protein serine/threonine kinase activity
- Specific Function
- Mediates apoptosis and actin stress fiber dissolution.
- Gene Name
- SLK
- Uniprot ID
- Q9H2G2
- Uniprot Name
- STE20-like serine/threonine-protein kinase
- Molecular Weight
- 142693.96 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- 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. [Article]
- 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. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
References
- Skoglund K, Moreno SB, Baytar M, Jonsson JI, Green H: ABCB1 haplotypes do not influence transport or efficacy of tyrosine kinase inhibitors in vitro. Pharmgenomics Pers Med. 2013 Aug 20;6:63-72. doi: 10.2147/PGPM.S45522. eCollection 2013. [Article]
Drug created at March 19, 2008 16:41 / Updated at November 24, 2023 04:34