Motexafin lutetium

Identification

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Name
Motexafin lutetium
Accession Number
DB05296
Type
Small Molecule
Groups
Investigational
Description

Motexafin lutetium (MLu) is a second-generation photosensitizer for photodynamic therapy (PDT) of cancer. It belongs to the family of drugs called metallotexaphyrins. Also called lutetium texaphyrin. Motexafin lutetium is a pentadentate aromatic metallotexaphyrin with photosensitizing properties.

Structure
Thumb
Synonyms
  • Lutetium texaphyrin anhydrous
  • Motexafin lutetium anhydrous
Product Ingredients
IngredientUNIICASInChI Key
Motexafin lutetium hydrate0A85BJ22L6156436-90-7WIQKYZYFTAEWBF-IOYKFIIZSA-L
International/Other Brands
Antrin / Lutrin / Optrin
Categories
UNII
0V38NF6N89
CAS number
246252-04-0
Weight
Average: 1166.136
Monoisotopic: 1165.44836
Chemical Formula
C52H72LuN5O14
InChI Key
ZCISRIHHEXSWIR-WRIGXHCHSA-L
InChI
InChI=1S/C48H66N5O10.2C2H4O2.Lu/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
lutetium(3+) 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[20.2.1.1^{3,6}.1^{8,11}.0^{14,19}]heptacosa-1,3,5,7,9,11(26),12,14,16,18,20,22(25),23-tridecaen-27-ide diacetate
SMILES
[Lu+3].CC([O-])=O.CC([O-])=O.CCC1=C2[N-]C(\C=C3/N=C(/C=N/C4=CC(OCCOCCOCCOC)=C(OCCOCCOCCOC)C=C4\N=C\C4=N\C(=C/2)\C(CCCO)=C4C)C(C)=C3CCCO)=C1CC

Pharmacology

Indication

Investigated for use/treatment in brain cancer, breast cancer, cervical dysplasia/cancer, prostate cancer, cancer/tumors (unspecified), coronary artery disease, macular degeneration, and peripheral vascular disease.

Pharmacodynamics
Not Available
Mechanism of action

Motexafin lutetium has the potential to combine the features of selective localization, ability to be activated by deeply penetrating far-red light, low incidence of skin photosensitization and water solubility. The product is in clinical development as a treatment for several types of solid tumors (as Lutrin), age-related macular degeneration (as Optrin), atherosclerosis and prevention of restenosis (as Antrin). Motexafin lutetium preferentially accumulates in tumor cells due to their increased rates of metabolism and absorbs light, forming an extended high energy conformational state that produces high quantum yields of singlet oxygen, resulting in local cytotoxic effects.

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
DrugInteraction
Porfimer sodiumMotexafin lutetium may increase the photosensitizing activities of Porfimer sodium.
VerteporfinMotexafin lutetium may increase the photosensitizing activities of Verteporfin.
Additional Data Available
  • Extended Description
    Extended Description

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

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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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Food Interactions
Not Available

References

General References
  1. Chen Z, Woodburn KW, Shi C, Adelman DC, Rogers C, Simon DI: Photodynamic therapy with motexafin lutetium induces redox-sensitive apoptosis of vascular cells. Arterioscler Thromb Vasc Biol. 2001 May;21(5):759-64. [PubMed:11348871]
  2. Ross HM, Smelstoys JA, Davis GJ, Kapatkin AS, Del Piero F, Reineke E, Wang H, Zhu TC, Busch TM, Yodh AG, Hahn SM: Photodynamic therapy with motexafin lutetium for rectal cancer: a preclinical model in the dog. J Surg Res. 2006 Oct;135(2):323-30. Epub 2006 May 2. [PubMed:16650871]
External Links
PubChem Compound
3081907
PubChem Substance
175426971
ChemSpider
8095581
Wikipedia
Motexafin_lutetium

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1TerminatedPreventionCervical Cancers / Cervical Intraepithelial Neoplasia Grade 2 / Cervical Intraepithelial Neoplasia Grade 31
1TerminatedTreatmentAdenocarcinoma of the Prostate / Recurrent Prostate Cancer / Stage I Prostate Cancer / Stage IIA Prostate Cancer / Stage IIB Prostate Cancer1
Not AvailableTerminatedDiagnosticAdvanced Adult Primary Liver Cancer / Advanced Gastric Cancer / Carcinoma of the Appendix / Fallopian Tube Cancer / Gastrointestinal Stromal Tumors / Localized Extrahepatic Bile Duct Cancer / Localized Gallbladder Cancer / Localized Gastrointestinal Carcinoid Tumor / Localized Resectable Adult Primary Liver Cancer / Localized Unresectable Adult Primary Liver Cancer / Malignant Neoplasm of Stomach Stage II / Metastatic Colon Cancer / Metastatic Gastrointestinal Carcinoid Tumor / Non-Small Cell Lung Cancer Recurrent / Ovarian Sarcoma / Ovarian Stromal Cancer / Primary Peritoneal Cavity Cancer / Recurrent Adult Primary Liver Cancer / Recurrent Adult Soft Tissue Sarcoma / Recurrent Colon Cancer / Recurrent Extrahepatic Bile Duct Cancer / Recurrent Gallbladder Cancer / Recurrent Gastric Cancer / Recurrent Gastrointestinal Carcinoid Tumor / Recurrent Ovarian Epithelial Cancer / Recurrent Ovarian Germ Cell Tumor / Recurrent Pancreatic Cancer / Recurrent Rectal Cancer / Recurrent Small Intestine Cancer / Recurrent Uterine Sarcoma / Regional Gastrointestinal Carcinoid Tumor / Small Intestine Adenocarcinoma / Small Intestine Leiomyosarcoma / Small Intestine Lymphoma / Stage 0 Non-small Cell Lung Cancer / Stage I Adult Soft Tissue Sarcoma / Stage I Colon Cancer / Stage I Gastric Cancer / Stage I Non-Small Cell Lung Cancer / Stage I Ovarian Epithelial Cancer / Stage I Ovarian Germ Cell Tumor / Stage I Pancreatic Cancer / Stage I Rectal Cancer / Stage I Uterine Sarcoma / Stage II Adult Soft Tissue Sarcoma / Stage II Colon Cancer / Stage II Non-Small Cell Lung Cancer / Stage II Ovarian Epithelial Cancer / Stage II Ovarian Germ Cell Tumor / Stage II Pancreatic Cancer / Stage II Rectal Cancer / Stage II Uterine Sarcoma / Stage III Adult Soft Tissue Sarcoma / Stage III Colon Cancer / Stage III Gastric Cancer / Stage III Ovarian Epithelial Cancer / Stage III Ovarian Germ Cell Tumor / Stage III Pancreatic Cancer / Stage III Rectal Cancer / Stage III Uterine Sarcoma / Stage IIIA Non-Small Cell Lung Cancer / Stage IIIb Non-small Cell Lung Cancer / Stage IV Adult Soft Tissue Sarcoma / Stage IV Non-Small Cell Lung Cancer / Stage IV Ovarian Epithelial Cancer / Stage IV Ovarian Germ Cell Tumor / Stage IV Pancreatic Cancer / Stage IV Rectal Cancer / Stage IV Uterine Sarcoma / Unresectable Extrahepatic Bile Duct Cancer / Unresectable Gallbladder Cancer1

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 Solubility0.00532 mg/mLALOGPS
logP4.99ALOGPS
logP6.76ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)15.62ChemAxon
pKa (Strongest Basic)2.45ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count15ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area178.75 Å2ChemAxon
Rotatable Bond Count28ChemAxon
Refractivity243.08 m3·mol-1ChemAxon
Polarizability106.08 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8734
Blood Brain Barrier-0.7339
Caco-2 permeable-0.6221
P-glycoprotein substrateSubstrate0.8853
P-glycoprotein inhibitor INon-inhibitor0.5372
P-glycoprotein inhibitor IINon-inhibitor0.8542
Renal organic cation transporterNon-inhibitor0.757
CYP450 2C9 substrateNon-substrate0.8583
CYP450 2D6 substrateNon-substrate0.8056
CYP450 3A4 substrateSubstrate0.5944
CYP450 1A2 substrateNon-inhibitor0.5684
CYP450 2C9 inhibitorNon-inhibitor0.676
CYP450 2D6 inhibitorNon-inhibitor0.8557
CYP450 2C19 inhibitorNon-inhibitor0.7248
CYP450 3A4 inhibitorNon-inhibitor0.5218
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8409
Ames testNon AMES toxic0.6034
CarcinogenicityNon-carcinogens0.9072
BiodegradationNot ready biodegradable0.9768
Rat acute toxicity2.5917 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8781
hERG inhibition (predictor II)Non-inhibitor0.6777
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

Drug created on November 18, 2007 11:23 / Updated on June 04, 2019 06:15