Studies using confocal fluorescence microscopy on adenocarcinomas have revealed that temoporfin is mostly found in the Golgi apparatus and endoplasmic reticulum, with limited localization in lysosomes and mitochondria [1].

After 4 hours, the amount of temoporfin (0.1–0.3 mg/kg) in the liver tissue dropped off quickly, however 48 hours later, the amount in the tumor tissue stayed high.

Absorption, Distribution and Excretion
Tmax is 2-4 h after intravenous administration. Plasma concentration initially decreases rapidly then slowly rises to reach peak serum concentration.
Data on elimination in humans is limited. 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.
The volume of distribution is 0.34-0.46 L/kg. Temoporfin is known to distribute into the tissues and preferentially collects in tumour tissue.
Temoporfin is cleared at a rate of 3.9-4.1 mL/h/kg.

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Metabolism / Metabolites
The exact metabolic reactions Temoporfin undergoes are unknown. The drug metabolites have been identified as conjugates but specific information is unavailable.

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Biological Half-Life
Terminal plasma half life is 65 h. 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.

Protein Binding
Temoporfin is 85-88% bound to plasma proteins. Temoporfin initially binds and aggregates to an unknown high density protein. 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.

[1]. Temoporfin (Foscan®, 5,10,15,20-tetra(m-hydroxyphenyl)chlorin)--a second-generation photosensitizer. Photochem Photobiol. 2011 Nov-Dec;87(6):1240-96.

[2]. Effective treatment of liver metastases with photodynamic therapy, using the second-generation photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC), in a rat model. Br J Cancer. 1999 Oct;81(4):600-8.

[3]. Photodynamic therapy with conventional and PEGylated liposomal formulations of mTHPC (temoporfin): comparison of treatment efficacy and distribution characteristics in vivo. Int J Nanomedicine. 2013;8:3817-31.

Temoporfin is a member of chlorins. It has a role as a photosensitizing agent.
Temoporfin is a photosensitizing agent used in the treatment of squamous cell carcinoma of the head and neck. It was first authorized for market by the European Medicines Agency in October 2001. It is currently available under the brand name Foscan.
Temoporfin is a synthetic light-activated chlorin with photodynamic activity. Upon systemic administration, temoporfin distributes throughout the body and is taken up by tumor cells. Upon stimulation of temoporfin by non-thermal laser light (at 652 nm), and in the presence of oxygen, this agent produces highly reactive short-lived singlet oxygen and other reactive oxygen radicals, resulting in local damage to tumor cells. This may kill tumor cells and may reduce the tumor size.

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Drug 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.
FDA Label
Foscan is indicated for the palliative treatment of patients with advanced head and neck squamous cell carcinoma failing prior therapies and unsuitable for radiotherapy, surgery or systemic chemotherapy.

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Mechanism of Action
Temoporfin is excited from ground state to the first excited singlet state by the application of 652 nm light. It is then thought to undergo intersystem crossing to an excited triplet state which is longer lived and able to interact with surrounding molecules. 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. 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.

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Pharmacodynamics
Temoporfin is a photosensitizing agent. It enters cancer cells and is activated via light to produce reactive species which destroy the cell.

C44H32N4O4

680.75

680.242

122341-38-2

60751

Purple to black solid powder

1.4±0.1 g/cm3

1.735

9.17

6

6

4

52

1090

0

LYPFDBRUNKHDGX-UHFFFAOYSA-N

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

3-[10,15,20-tris(3-hydroxyphenyl)-2,3,22,24-tetrahydroporphyrin-5-yl]phenol

EF 9; mTHPC; m-THPC

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~20.83 mg/mL (~30.60 mM)

Solubility in Formulation 1: ≥ 1 mg/mL (1.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 1 mg/mL (1.47 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)