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Identification
Namemotexafin gadolinium
Accession NumberDB05428
TypeSmall Molecule
GroupsInvestigational
DescriptionMotexafin gadolinium is studied in the treatment of cancer by Pharmacyclics. It may make tumor cells more sensitive to radiation therapy, improve tumor images using magnetic resonance imaging (MRI), and kill cancer cells. It belongs to the family of drugs called metalloporphyrin complexes. Also called gadolinium texaphyrin.
Structure
Thumb
SynonymsNot Available
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
XcytrinNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII0BG5NE3APZ
CAS numberNot Available
WeightAverage: 1148.4
Monoisotopic: 1148.43167757
Chemical FormulaC52H72GdN5O14
InChI KeyVAZLWPAHMORDGR-WRIGXHCHSA-L
InChI
InChI=1S/C48H66N5O10.2C2H4O2.Gd/c1-7-35-36(8-2)40-28-42-38(12-10-14-55)34(4)46(53-42)32-50-44-30-48(63-26-24-61-22-20-59-18-16-57-6)47(62-25-23-60-21-19-58-17-15-56-5)29-43(44)49-31-45-33(3)37(11-9-13-54)41(52-45)27-39(35)51-40;2*1-2(3)4;/h27-32,54-55H,7-26H2,1-6H3;2*1H3,(H,3,4);/q-1;;;+3/p-2/b39-27-,40-28-,41-27-,42-28-,45-31-,46-32-,49-31+,49-43+,50-32+,50-44+;;;
IUPAC Name
gadolinium(3+) ion 4,5-diethyl-9,24-bis(3-hydroxypropyl)-16,17-bis({2-[2-(2-methoxyethoxy)ethoxy]ethoxy})-10,23-dimethyl-13,20,25,26,27-pentaazapentacyclo[20.2.1.1³,⁶.1⁸,¹¹.0¹⁴,¹⁹]heptacosa-1(25),2,4,6,8(26),9,11,13,15,17,19,21,23-tridecaen-27-ide diacetate
SMILES
[Gd+3].CC([O-])=O.CC([O-])=O.CCC1=C(CC)/C2=C/C3=N/C(=C\N=C4/C=C(OCCOCCOCCOC)C(OCCOCCOCCOC)=C/C/4=N\C=C4/N=C(/C=C\1\[N-]\2)C(CCCO)=C4C)/C(C)=C3CCCO
Pharmacology
IndicationInvestigated for use/treatment in brain cancer, cancer/tumors (unspecified), lung cancer, and lymphoma (non-hodgkin's).
Structured Indications Not Available
PharmacodynamicsNot Available
Mechanism of actionMotexafin gadolinium (Xcytrin) is Pharmacyclics' most advanced anti-cancer product candidate, a small-molecule drug with a novel mechanism of action. Xcytrin accumulates selectively in cancer cells due to their increased rates of metabolism. Once inside the cell, Xcytrin induces apoptosis (programmed cell death) by disrupting redox-dependent pathways. Xcytrin inhibits the enzyme thioredoxin reductase, which is a tumor growth promoter. This mechanism provides the opportunity to use Xcytrin in a wide range of cancers. Xcytrin is paramagnetic, and therefore is detectable by magnetic resonance imaging (MRI), allowing the visualization of the drug in tumors.
TargetKindPharmacological actionActionsOrganismUniProt ID
Thioredoxin reductase 1, cytoplasmicProteinunknownNot AvailableHumanQ16881 details
Thioredoxin reductase 2, mitochondrialProteinunknownNot AvailableHumanQ9NNW7 details
Ribonucleoside-diphosphate reductase subunit M2ProteinunknownNot AvailableHumanP31350 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of motexafin gadolinium.Approved
AnvirzelAnvirzel may decrease the cardiotoxic activities of motexafin gadolinium.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of motexafin gadolinium.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with motexafin gadolinium.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of motexafin gadolinium.Approved, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of motexafin gadolinium.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of motexafin gadolinium.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of motexafin gadolinium.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with motexafin gadolinium.Approved, Investigational
OuabainOuabain may decrease the cardiotoxic activities of motexafin gadolinium.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with motexafin gadolinium.Approved, Vet Approved
Porfimermotexafin gadolinium may increase the photosensitizing activities of Porfimer.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of motexafin gadolinium.Approved, Investigational
Verteporfinmotexafin gadolinium may increase the photosensitizing activities of Verteporfin.Approved, Investigational
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Evens AM: Motexafin gadolinium: a redox-active tumor selective agent for the treatment of cancer. Curr Opin Oncol. 2004 Nov;16(6):576-80. [PubMed:15627019 ]
  2. Forouzannia A, Richards GM, Khuntia D, Mehta MP: Motexafin gadolinium: a novel radiosensitizer for brain tumors. Expert Rev Anticancer Ther. 2007 Jun;7(6):785-94. [PubMed:17555388 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.5376
Blood Brain Barrier-0.715
Caco-2 permeable-0.5913
P-glycoprotein substrateSubstrate0.8533
P-glycoprotein inhibitor INon-inhibitor0.6742
P-glycoprotein inhibitor IINon-inhibitor0.8876
Renal organic cation transporterNon-inhibitor0.7757
CYP450 2C9 substrateNon-substrate0.8708
CYP450 2D6 substrateNon-substrate0.8061
CYP450 3A4 substrateSubstrate0.5704
CYP450 1A2 substrateNon-inhibitor0.6095
CYP450 2C9 inhibitorNon-inhibitor0.7021
CYP450 2D6 inhibitorNon-inhibitor0.8511
CYP450 2C19 inhibitorNon-inhibitor0.7157
CYP450 3A4 inhibitorNon-inhibitor0.5474
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8753
Ames testNon AMES toxic0.6036
CarcinogenicityNon-carcinogens0.9027
BiodegradationNot ready biodegradable0.8517
Rat acute toxicity2.5734 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8697
hERG inhibition (predictor II)Non-inhibitor0.7296
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0122 mg/mLALOGPS
logP4.95ALOGPS
logP6.76ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)15.62ChemAxon
pKa (Strongest Basic)2.19ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count15ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area178.75 Å2ChemAxon
Rotatable Bond Count28ChemAxon
Refractivity243.08 m3·mol-1ChemAxon
Polarizability103.73 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
ClassificationNot classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Thioredoxin-disulfide reductase activity
Specific Function:
Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a ...
Gene Name:
TXNRD1
Uniprot ID:
Q16881
Molecular Weight:
70905.58 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Thioredoxin-disulfide reductase activity
Specific Function:
Maintains thioredoxin in a reduced state. Implicated in the defenses against oxidative stress. May play a role in redox-regulated cell signaling.
Gene Name:
TXNRD2
Uniprot ID:
Q9NNW7
Molecular Weight:
56506.275 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
Specific Function:
Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. Inhibits Wnt signaling.
Gene Name:
RRM2
Uniprot ID:
P31350
Molecular Weight:
44877.25 Da
Comments
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Drug created on November 18, 2007 11:24 / Updated on August 17, 2016 12:24