Identification

Name
Bosutinib
Accession Number
DB06616
Type
Small Molecule
Groups
Approved
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.

Structure
Thumb
Synonyms
  • 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methyl-1-piperazinyl)propoxy)-3-quinolinecarbonitrile
  • Bosulif®
  • Bosutinib
  • Bosutinib Monohydrate
  • SKI 606
External IDs
SK-606 / SKI-606
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BosulifTablet, film coated100 mgOralPfizer Europe Ma Eeig2013-03-27Not applicableEu
BosulifTablet100 mgOralPfizer2014-04-24Not applicableCanada
BosulifTablet, film coated100 mg/1OralPfizer Laboratories Div Pfizer Inc2012-09-04Not applicableUs
BosulifTablet, film coated500 mgOralPfizer Europe Ma Eeig2013-03-27Not applicableEu
BosulifTablet, film coated100 mgOralPfizer Europe Ma Eeig2013-03-27Not applicableEu
BosulifTablet, film coated400 mg/1OralPfizer Laboratories Div Pfizer Inc2017-10-01Not applicableUs
BosulifTablet, film coated100 mg/1OralU.S. Pharmaceuticals2012-09-04Not applicableUs
BosulifTablet, film coated500 mgOralPfizer Europe Ma Eeig2013-03-27Not applicableEu
BosulifTablet500 mgOralPfizer2014-03-24Not applicableCanada
BosulifTablet, film coated500 mg/1OralPfizer Laboratories Div Pfizer Inc2012-09-04Not applicableUs
Categories
UNII
5018V4AEZ0
CAS number
380843-75-4
Weight
Average: 530.446
Monoisotopic: 529.164745233
Chemical Formula
C26H29Cl2N5O3
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

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
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.

TargetActionsOrganism
ABreakpoint cluster region protein
inhibitor
Human
ATyrosine-protein kinase ABL1
inhibitor
Human
UTyrosine-protein kinase LynNot AvailableHuman
UTyrosine-protein kinase HCK
inhibitor
Human
UProto-oncogene tyrosine-protein kinase Src
inhibitor
Human
UCyclin-dependent kinase 2
inhibitor
Human
UDual specificity mitogen-activated protein kinase kinase 1
inhibitor
Human
UDual specificity mitogen-activated protein kinase kinase 2
inhibitor
Human
UMitogen-activated protein kinase kinase kinase 2
inhibitor
Human
UCalcium/calmodulin-dependent protein kinase type II subunit gamma
inhibitor
Human
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

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
PathwayCategory
Bosutinib Inhibition of BCR-ABLDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbemaciclibThe serum concentration of Bosutinib can be increased when it is combined with Abemaciclib.
AcetaminophenThe serum concentration of Bosutinib can be increased when it is combined with Acetaminophen.
AcetazolamideThe metabolism of Bosutinib can be decreased when combined with Acetazolamide.
Acetyl sulfisoxazoleThe serum concentration of Bosutinib can be increased when it is combined with Acetyl sulfisoxazole.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Bosutinib.
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Bosutinib.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Bosutinib.
AfatinibThe serum concentration of Bosutinib can be increased when it is combined with Afatinib.
AlbendazoleThe serum concentration of Bosutinib can be increased when it is combined with Albendazole.
AlclometasoneThe risk or severity of adverse effects can be increased when Bosutinib is combined with Alclometasone.
Food Interactions
  • When given with a high fat meal, the Cmax and AUC of bosutinib increased 1.8- and 1.7-fold, respectively.

References

General References
  1. 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]
  2. 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]
  3. Link [Link]
External Links
Human Metabolome Database
HMDB0240205
KEGG Drug
D03252
PubChem Compound
5328940
PubChem Substance
175427079
ChemSpider
4486102
BindingDB
4552
ChEBI
39112
ChEMBL
CHEMBL288441
HET
DB8
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Bosutinib
ATC Codes
L01XE14 — Bosutinib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
3soa / 3ue4 / 4mxo / 4mxx / 4mxy / 4mxz / 4otw / 4qmn / 5ajq / 5i9x
show 3 more
FDA label
Download (326 KB)
MSDS
Download (97.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableCancer, Breast / Chronic Myeloid Leukemia (CML)1
1CompletedNot AvailableCancer, Breast / Leukemias / Tumors1
1CompletedNot AvailableHealthy Volunteers2
1CompletedBasic ScienceHealthy Volunteers2
1CompletedTreatmentHealthy Volunteers8
1CompletedTreatmentNeoplasms1
1CompletedTreatmentPhiladelphia Chromosome Positive (Ph+) Chronic Myeloid Leukemia (CML)1
1CompletedTreatmentRenal Disease, End-Stage / Renal Insufficiency, Acute / Renal Insufficiency,Chronic1
1CompletedTreatmentTumors1
1Enrolling by InvitationTreatmentDementias / Mild Cognitive Impairment (MCI)1
1RecruitingTreatmentAdvanced thymic carcinoma / Bladder Cancers / Cancer of the Ovary / Lung Cancer Non-Small Cell Cancer (NSCLC) / Malignant Peritoneal Neoplasm / Mesothelioma / Thymus Cancer / Uterine Cervical Cancer1
1TerminatedTreatmentMalignant Neoplasm of Pancreas1
1, 2CompletedTreatmentChronic Myeloid Leukemia (CML)1
1, 2RecruitingTreatmentLeukemias2
1, 2TerminatedTreatmentAdvanced Breast Cancer (Parts 1 and 2) / Advanced Cholangiocarcinoma (Part 1) / Advanced Colorectal Cancer (Part 1) / Advanced Glioblastoma Multiforme (Part 1) / Advanced Pancreatic Cancer (Part 1)1
2Active Not RecruitingTreatmentChronic Myeloblastic Leukaemia1
2Active Not RecruitingTreatmentChronic Chronic myelogenous leukemia1
2CompletedTreatmentAutosomal Dominant Polycystic Kidney Disease (ADPKD)1
2CompletedTreatmentGlioblastomas1
2CompletedTreatmentNeoplasms Metastasis / Neoplasms, Breast1
2CompletedTreatmentChronic Chronic myelogenous leukemia1
2RecruitingTreatmentAdvanced Solid Tumors / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)2
2RecruitingTreatmentBCR-ABL Positive / Chronic / Leukemias / Myelogenous1
2RecruitingTreatmentChronic Myelogenous Leukaemia1
2RecruitingTreatmentChronic Myeloid Leukemia (CML)1
2RecruitingTreatmentChronic Chronic myelogenous leukemia1
2TerminatedTreatmentAdvanced Breast Cancer1
2TerminatedTreatmentCancer, Breast1
3Active Not RecruitingTreatmentLeukemia, Myelogenous, Chronic, Breakpoint Cluster Region-Abelson Proto-oncogene (BCR-ABL) Positive1
3CompletedTreatmentChronic Myeloid Leukemia (CML)1
3RecruitingTreatmentChronic Chronic myelogenous leukemia1
4Active Not RecruitingTreatmentPreviously Treated PH + CML1
Not AvailableActive Not RecruitingNot AvailableChronic Myeloid Leukemia (CML)1
Not AvailableActive Not RecruitingNot AvailableChronic Chronic myelogenous leukemia1
Not AvailableCompletedNot AvailableChronic Myeloid Leukemia (CML)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral100 mg
TabletOral500 mg
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral100 mg
Tablet, film coatedOral400 mg/1
Tablet, film coatedOral500 mg/1
Tablet, film coatedOral500 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6002008No1998-03-272018-03-27Us
US7417148No2006-01-232026-01-23Us
USRE42376No1999-09-242019-09-24Us
US7767678No2006-11-232026-11-23Us
US7919625No2005-12-112025-12-11Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0095 mg/mLALOGPS
logP4.87ALOGPS
logP4.09ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)15.48ChemAxon
pKa (Strongest Basic)8.43ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area82.88 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity142.12 m3·mol-1ChemAxon
Polarizability56.14 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9823
Blood Brain Barrier+0.9272
Caco-2 permeable+0.6542
P-glycoprotein substrateSubstrate0.7601
P-glycoprotein inhibitor IInhibitor0.8409
P-glycoprotein inhibitor IIInhibitor0.9108
Renal organic cation transporterInhibitor0.5663
CYP450 2C9 substrateNon-substrate0.854
CYP450 2D6 substrateNon-substrate0.6953
CYP450 3A4 substrateSubstrate0.6987
CYP450 1A2 substrateInhibitor0.5606
CYP450 2C9 inhibitorNon-inhibitor0.7372
CYP450 2D6 inhibitorNon-inhibitor0.5136
CYP450 2C19 inhibitorNon-inhibitor0.5725
CYP450 3A4 inhibitorInhibitor0.5
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7021
Ames testAMES toxic0.5922
CarcinogenicityNon-carcinogens0.8869
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4201 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6147
hERG inhibition (predictor II)Inhibitor0.7754
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-0092000000-68183c460c3cf8e08c01
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001l-1900080000-86f44693fc4098040447

Taxonomy

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
4-aminoquinoline / Methoxyaniline / Aminophenyl ether / Anisole / 1,3-dichlorobenzene / Phenol ether / Aniline or substituted anilines / Methoxybenzene / Phenoxy compound / Alkyl aryl ether
show 30 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tertiary amino compound, aromatic ether, nitrile, dichlorobenzene, aminoquinoline, N-methylpiperazine (CHEBI:39112)

Targets

Kind
Protein
Organism
Human
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
Kind
Protein
Organism
Human
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
Kind
Protein
Organism
Human
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
Kind
Protein
Organism
Human
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
Kind
Protein
Organism
Human
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
Details
6. Cyclin-dependent kinase 2
Kind
Protein
Organism
Human
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
  1. 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]
Kind
Protein
Organism
Human
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
  1. 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]
Kind
Protein
Organism
Human
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
  1. 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]
Kind
Protein
Organism
Human
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
  1. 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]
Kind
Protein
Organism
Human
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
  1. 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

Kind
Protein
Organism
Human
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
  1. 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]
Kind
Protein
Organism
Human
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
  1. 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

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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 October 15, 2018 04:36