Identification
- Summary
Temoporfin is a photosensitizer used to treat squamous cell carcinomas of the head and neck.
- Generic Name
- Temoporfin
- DrugBank Accession Number
- DB11630
- Background
Temoporfin is a photosensitizing agent used in the treatment of squamous cell carcinoma of the head and neck Label. It was first authorized for market by the European Medicines Agency in October 2001. It is currently available under the brand name Foscan.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Temoporfin (DB11630)
- Weight
- Average: 680.764
Monoisotopic: 680.242355526 - Chemical Formula
- C44H32N4O4
- Synonyms
- 2,3-dihydro-5,10,15,20-tetra(m-hydroxyphenyl)porphyrin
- m-THPC
- meso-tetrahydroxyphenylchlorin
- Temoporfin
- External IDs
- EF-9
- EF9
Pharmacology
- Indication
For use in the treatment of patients with advanced squamous cell carcinoma of the head and neck failing standard therapies and who are unsuitable for radiotherapy, surgery, or systemic chemotherapy Label.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Symptomatic treatment of Advanced head and neck squamous cell carcinoma •••••••••••• - Contraindications & Blackbox Warnings
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Temoporfin is a photosensitizing agent Label. It enters cancer cells and is activated via light to produce reactive species which destroy the cell.
- Mechanism of action
Temoporfin is excited from ground state to the first excited singlet state by the application of 652 nm light 4,2. It is then thought to undergo intersystem crossing to an excited triplet state which is longer lived and able to interact with surrounding molecules 2. It is then thought to produce cytotoxic species by either a Type I or Type II reaction typical of agents used in photodynamic therapy. Type I involves either hydrogen abstraction of electron transfer from the excited photosensitizer to a substrate molecule to produce free radicals or radical ions. Type II reactions involve a similar reaction with oxygen as the substrate to produce reactive oxygen species. These reactive products cause oxidative damage to the cancer cell resulting in cell death.
There is evidence that photodynamic therapy with Temoporfin activates macrophages and increases phagocytosis 3. These activated macrophages also produce more tumour necrosis factor-α (TNF-α) and nitric oxide (NO). It is thought that this increase in macrophage activity contributes to the efficacy of therapy through phagocytosis of cancer cells and increased cell death signalling though TNF-α. The increase in NO production likely contributes to oxidative damage through reactive nitrogen species.
- Absorption
Tmax is 2-4 h after intravenous administration Label. Plasma concentration initially decreases rapidly then slowly rises to reach peak serum concentration 4.
- Volume of distribution
The volume of distribution is 0.34-0.46 L/kg 4. Temoporfin is known to distribute into the tissues and preferentially collects in tumour tissue.
- Protein binding
Temoporfin is 85-88% bound to plasma proteins Label,4. Temoporfin initially binds and aggregates to an unknown high density protein 1. This makes up about 70% of the bound drug immediately after administration. The remainder is bound to plasma lipoproteins with 22% bound to high density lipoprotein (HDL), 4% bound to low density lipoprotein (LDL), and 4% bound to very low density lipoprotein (VLDL). Within 24 hours after administration, Temoporfin undergoes redistribution to lipoproteins with about 73% bound to HDL, 8% bound to LDL, and 3% bound to VLDL. Only 17% remains bound to the unknown high density protein after redistribution.
- Metabolism
The exact metabolic reactions Temoporfin undergoes are unknown. The drug metabolites have been identified as conjugates but specific information is unavailable.
- Route of elimination
Data on elimination in humans is limited Label,4. Animal data indicates Temoporfin is eliminated solely by the liver with two conjugated metabolites being excreted through bile. No enterohepatic recirculation has been observed with these metabolites.
- Half-life
Terminal plasma half life is 65 h Label. Elimination of Temoporfin is bi-exponential with the intial phase having a half-life of 30 h and a terminal half-life of 61-88 h 4.
- Clearance
Temoporfin is cleared at a rate of 3.9-4.1 mL/h/kg 4.
- Adverse Effects
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Mice and rats experienced swelling and darkening of exposed tissue at single dosages of >0.85 mg/kg under normal lighting 4. Systemic toxicity presented as reduced red blood cell and platelet counts and increased white blood cell counts and liver and spleen weights. Skin inflammation, pycnotic spermatocytes and increased extramedullary haematopoiesis in spleen and the lymph nodes was also observed. Under low-light conditions mild phototoxicity was observed only at high doses.
Severe phototoxicity has been seen in rats with repeated doses of up to 1 mg/kg/day under normal lighting 4. This effect is less severe under low-light conditions. Two weeks of repeated doses of 0.5-0.6 mg/kg/day resulted in inflammation of the injection site and skin in rats. At 0.3 mg/kg/day under low-light in rats, the only effect seen was an increase in white blood cell counts.
In beagle dogs recieving repeated doses of up to 3mg/kg/day under low-light conditions, reddening of the skin and injection site inflammation was seen 4. Serious injection site damage was observed.
- Pathways
- Not Available
- 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 softwareAmbroxol The risk or severity of methemoglobinemia can be increased when Temoporfin is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Temoporfin is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Temoporfin is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Temoporfin is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when Temoporfin is combined with Bupivacaine. - Food Interactions
- No interactions found.
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.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Foscan Injection, solution 1 mg/ml Intravenous Biolitec Pharma Ltd 2016-09-08 Not applicable EU 
Foscan Injection, solution 1 mg/ml Intravenous Biolitec Pharma Ltd 2016-09-08 Not applicable EU Foscan Injection, solution 1 mg/ml Intravenous Biolitec Pharma Ltd 2016-09-08 Not applicable EU
Categories
- ATC Codes
- L01XD05 — Temoporfin
- Drug Categories
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Biological Factors
- Dermatologicals
- Heterocyclic Compounds, Fused-Ring
- Narrow Therapeutic Index Drugs
- Photosensitizing Agents
- Pigments, Biological
- Porphyrins
- Radiation-Sensitizing Agents
- Sensitizers Used in Photodynamic/radiation Therapy
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- FU21S769PF
- CAS number
- 122341-38-2
- InChI Key
- LYPFDBRUNKHDGX-LWQDQPMZSA-N
- InChI
- InChI=1S/C44H32N4O4/c49-29-9-1-5-25(21-29)41-33-13-15-35(45-33)42(26-6-2-10-30(50)22-26)37-17-19-39(47-37)44(28-8-4-12-32(52)24-28)40-20-18-38(48-40)43(36-16-14-34(41)46-36)27-7-3-11-31(51)23-27/h1-17,19,21-24,46-47,49-52H,18,20H2/b41-33-,41-34-,42-35-,42-37-,43-36-,43-38-,44-39-,44-40-
- IUPAC Name
- 3-[7,12,17-tris(3-hydroxyphenyl)-21,22,23,24-tetraazapentacyclo[16.2.1.1³,⁶.1⁸,¹¹.1¹³,¹⁶]tetracosa-1,3,5,7,11(23),12,14,16,18(21),19-decaen-2-yl]phenol
- SMILES
- OC1=CC=CC(=C1)C-1=C2\CCC(=N2)\C(=C2/N\C(\C=C2)=C(/C2=N/C(/C=C2)=C(\C2=CC=C\-1N2)C1=CC(O)=CC=C1)C1=CC(O)=CC=C1)\C1=CC(O)=CC=C1
References
- General References
- Hopkinson HJ, Vernon DI, Brown SB: Identification and partial characterization of an unusual distribution of the photosensitizer meta-tetrahydroxyphenyl chlorin (temoporfin) in human plasma. Photochem Photobiol. 1999 Apr;69(4):482-8. [Article]
- Sharman WM, Allen CM, van Lier JE: Photodynamic therapeutics: basic principles and clinical applications. Drug Discov Today. 1999 Nov;4(11):507-517. [Article]
- Coutier S, Bezdetnaya L, Marchal S, Melnikova V, Belitchenko I, Merlin JL, Guillemin F: Foscan (mTHPC) photosensitized macrophage activation: enhancement of phagocytosis, nitric oxide release and tumour necrosis factor-alpha-mediated cytolytic activity. Br J Cancer. 1999 Sep;81(1):37-42. doi: 10.1038/sj.bjc.6690648. [Article]
- EMA: Temoporfin Scientific Discussion [Link]
- External Links
- KEGG Drug
- D06066
- KEGG Compound
- C11730
- ChemSpider
- 54754
- 115243
- ChEBI
- 9437
- ChEMBL
- CHEMBL500576
- Wikipedia
- Temoporfin
- FDA label
- Download (314 KB)
- MSDS
- Download (23.9 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 2 Completed Treatment Cholangiocarcinoma / Hilar Cholangiocarcinoma / Tumor 1 2 Terminated Treatment Squamous Cell Carcinoma of the Head and Neck (SCCHN) 1 2 Unknown Status Treatment Head And Neck Cancer 1 2 Unknown Status Treatment Nasopharyngeal Carcinoma (NPC) 1 2 Unknown Status Treatment Non-curative Resectable Bile Duct Carcinoma 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Intravenous Injection, solution Intravenous 1 mg/ml - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source logP 9.21 Chemaxon pKa (Strongest Acidic) 9.12 Chemaxon pKa (Strongest Basic) 5.6 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 6 Chemaxon Polar Surface Area 138.28 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 201.34 m3·mol-1 Chemaxon Polarizability 76.61 Å3 Chemaxon Number of Rings 9 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 271.1144825 predictedDarkChem Lite v0.1.0 [M-H]- 250.68147 predictedDeepCCS 1.0 (2019) [M+H]+ 276.1322825 predictedDarkChem Lite v0.1.0 [M+H]+ 252.57687 predictedDeepCCS 1.0 (2019) [M+Na]+ 258.63416 predictedDeepCCS 1.0 (2019)
Drug created at October 17, 2016 21:26 / Updated at February 21, 2021 18:53