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
Peak time (Tmax) is reached 2–4 hours after intravenous administration. Plasma concentration initially decreases rapidly, then slowly rises to peak serum concentration. Limited data are available regarding human elimination. Animal data show that temopofen is eliminated solely by the liver, with its two conjugated metabolites excreted via bile. Enterohepatic circulation of these metabolites has not been observed. Volume of distribution is 0.34–0.46 L/kg. Temopofen is known to distribute in tissues and preferentially accumulate in tumor tissue. The clearance of temopofen is 3.9–4.1 mL/h/kg. Metabolisms/Metabolites The exact metabolic response of temopofen is unknown. Drug metabolites have been identified as conjugates, but specific information is unavailable. Biological Half-Life The terminal plasma half-life is 65 hours. Temopofen exhibits a double exponential decay in elimination, with an initial half-life of 30 hours and a terminal half-life of 61-88 hours.

Protein Binding
Temopofen binds to plasma proteins at a rate of 85-88%. Temopofen initially binds to and aggregates with an unknown high-density lipoprotein (HDL). After administration, approximately 70% of the drug binds to this protein. The remaining drug binds to plasma lipoproteins, with 22% binding to HDL, 4% to LDL, and 4% to VLDL. Within 24 hours of administration, temopofen redistributes to lipoproteins, with approximately 73% binding to HDL, 8% to LDL, and 3% to VLDL. After redistribution, only 17% of the drug remains bound to the unknown HDL.

[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.

Temopofen belongs to the chlorine derivative class of compounds and is a photosensitizer. Temopofen is a photosensitizer used to treat squamous cell carcinoma of the head and neck. It first received marketing authorization from the European Medicines Agency in October 2001. It is currently marketed under the brand name Foscan. Temopofen is a synthetic photosensitizing chlorine compound with photodynamic activity. After systemic administration, temopofen is distributed throughout the body and absorbed by tumor cells. Under non-thermal laser irradiation (wavelength 652 nm) in the presence of oxygen, temopofen generates highly reactive, short-lived singlet oxygen and other reactive oxygen free radicals, leading to localized damage to tumor cells. This may kill tumor cells and shrink tumor volume. Drug Indications: For the treatment of patients with advanced squamous cell carcinoma of the head and neck who have not responded to standard therapy and are not eligible for radiotherapy, surgery, or systemic chemotherapy. FDA Label: Foscan is indicated for the palliative treatment of patients with advanced squamous cell carcinoma of the head and neck who have not responded to prior therapy and are not eligible for radiotherapy, surgery, or systemic chemotherapy.

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Mechanism of Action
Temopofen is excited from its ground state to the first excited singlet state under 652 nm light irradiation. Subsequently, it is thought to undergo intersystem crossing, entering a longer-lived excited triplet state capable of interacting with surrounding molecules. Afterward, it is thought to produce cytotoxic substances through type I or type II reactions commonly used in photodynamic therapy. Type I reactions involve the excited-state photosensitizer transferring hydrogen atoms or electrons to the substrate molecule, thereby generating free radicals or free radical ions. Type II reactions involve similar reactions, but with oxygen as the substrate, producing reactive oxygen species (ROS). These reactive products cause oxidative damage to cancer cells, ultimately leading to cell death. There is evidence that temopofen photodynamic therapy can activate macrophages and enhance their phagocytic activity. These activated macrophages also produce more tumor necrosis factor-α (TNF-α) and nitric oxide (NO). It is believed that enhanced macrophage activity improves therapeutic efficacy by phagocytizing cancer cells and enhancing TNF-α-mediated cell death signaling. Increased NO production may promote oxidative damage through reactive nitrogen species.

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Pharmacodynamics
Temopofen is a photosensitizer. After entering cancer cells, it is activated by light to produce reactive oxygen species, thereby destroying the cancer cells.

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.)