motexafin gadolinium

Identification

Name
motexafin gadolinium
Accession Number
DB05428
Type
Small Molecule
Groups
Investigational
Description

Motexafin 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
Synonyms
Not Available
External IDs
Not Available
Product Ingredients
Not Available
Approved Prescription Products
Not Available
Approved Generic Prescription Products
Not Available
Approved Over the Counter Products
Not Available
Unapproved/Other Products
Not Available
International/Other Brands
Xcytrin
Brand mixtures
Not Available
Categories
UNII
0BG5NE3APZ
CAS number
Not Available
Weight
Average: 1148.4
Monoisotopic: 1148.43167757
Chemical Formula
C52H72GdN5O14
InChI Key
VAZLWPAHMORDGR-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

Indication

Investigated for use/treatment in brain cancer, cancer/tumors (unspecified), lung cancer, and lymphoma (non-hodgkin's).

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Motexafin 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.

TargetActionsOrganism
UThioredoxin reductase 1, cytoplasmicNot AvailableHuman
UThioredoxin reductase 2, mitochondrialNot AvailableHuman
URibonucleoside-diphosphate reductase subunit M2Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of motexafin gadolinium.Approved
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
OleandrinAnvirzel may decrease the cardiotoxic activities of motexafin gadolinium.Experimental
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
Porfimer sodiummotexafin 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 Interactions
Not Available

References

Synthesis Reference
Not 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
PubChem Compound
158385
PubChem Substance
175427002
ChemSpider
139341
ChEBI
50161
Wikipedia
Motexafin_gadolinium
ATC Codes
Not Available
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0WithdrawnTreatmentBrain and Central Nervous System Tumors / Malignant Lymphomas / Neurotoxicity1
1CompletedDiagnosticBrain and Central Nervous System Tumors1
1CompletedTreatmentAdult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma1
1CompletedTreatmentAstrocytomas / Glioblastomas / Gliomas / Neoplasms, Brain / Oligodendrogliomas1
1CompletedTreatmentBrain and Central Nervous System Tumors3
1CompletedTreatmentCancer, Breast / Chronic Myeloproliferative Disorders / Colorectal Cancers / Head and Neck Carcinoma / Leukemias / Lung Cancers / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic/Myeloproliferative Diseases / Prostate Cancer / Small Intestine Cancer / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentCarcinoma, Bronchogenic / Non-Small-Cell Lung Carcinoma (NSCLC)1
1CompletedTreatmentExtrahepatic Bile Duct Cancer / Gallbladder Cancer / Malignant Neoplasm of Pancreas1
1CompletedTreatmentMalignant Neoplasm of Pancreas1
1CompletedTreatmentNeoplasms, Breast / Neoplasms, Gastrointestinal / Neoplasms, Lung / Neoplasms, Ovarian / Prostatic Neoplasms1
1CompletedTreatmentNeoplasms, Breast / Neoplasms, Lung / Neoplasms, Ovarian / Prostatic Neoplasms1
1CompletedTreatmentStage IIIA Non-Small Cell Lung Cancer1
1CompletedTreatmentUntreated Childhood Brain Stem Glioma1
1TerminatedTreatmentHead and Neck Carcinoma / Hypopharynx Cancer / Laryngeal Cancer / Oropharynx Cancers1
1, 2CompletedTreatmentAdult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma1
1, 2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias / Malignant Lymphomas / Small Lymphocytic Lymphoma (SLL)1
1, 2Unknown StatusTreatmentNon-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentAdenocarcinomas / Neoplasms, Lung / Non-Small-Cell Lung Carcinoma (NSCLC)1
2CompletedTreatmentBrain and Central Nervous System Tumors1
2CompletedTreatmentGenitourinary tract neoplasm / Neoplasms, Kidney / Renal Cell Adenocarcinoma / Urologic Neoplasms1
2CompletedTreatmentMalignant Lymphomas / Non-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentMultiple Myeloma (MM)1
2CompletedTreatmentUntreated Childhood Brain Stem Glioma1
2TerminatedTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
2TerminatedTreatmentLeukemia, Lymphocytic, Chronic / Leukemias1
2TerminatedTreatmentLung Cancers1
2TerminatedTreatmentNeoplasms Metastasis / Neoplasms, Brain1
2TerminatedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
2Unknown StatusTreatmentBrain and Central Nervous System Tumors1
2Unknown StatusTreatmentRenal Cancers1
3CompletedTreatmentNeoplasm Metastases / Neoplasms, Brain / Non-Small-Cell Lung Carcinoma (NSCLC)1
Not AvailableActive Not RecruitingDiagnosticLiver Cancer1
Not AvailableUnknown StatusScreeningCancer, Breast1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not 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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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 )

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not 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 enha...
Gene Name
TXNRD1
Uniprot ID
Q16881
Uniprot Name
Thioredoxin reductase 1, cytoplasmic
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
Uniprot Name
Thioredoxin reductase 2, mitochondrial
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
Uniprot Name
Ribonucleoside-diphosphate reductase subunit M2
Molecular Weight
44877.25 Da
Drug created on November 18, 2007 11:24 / Updated on September 01, 2017 11:24