Ecamsule does not have a traditional biological target; instead, it acts as a physical and chemical filter that protects against ultraviolet (UV) radiation. It provides protection in the wavelength range of 290-400 nm, with peak or optimal protection at approximately 345 nm. By absorbing UVA radiation, it prevents the cellular and molecular damage that can lead to skin conditions like polymorphous light eruption (PMLE).

The maximal absorbance of escamsule, a broad-spectrum UVA absorber, is 344 nm[1]. The sensitivity of wild-type Fibs E6/E7 cells to Ecamsule treatment (200–1600 μM) is higher [1]. ..The production of ROS brought on by UV and AAPH can be inhibited by escamsule [1]. ..With a maximum ROS reduction of 25.7% at the highest measured concentration of 1600 μM in the UV setting, the impact was dose-dependent. The oxidative stress caused by AAPH was decreased by 10.8% and the basal level was decreased by 16.9% at the same Ecamsule concentration[1]. ..At the maximum dose of 1600 μM, Ecamsule can boost viability in cells treated with AAPH [1].
In vitro, Ecamsule has been shown to reduce biological damage caused by solar radiation, including the formation of pyrimidine dimers and the accumulation of p53 protein. It counteracts UV and AAPH-induced ROS formation in a dose-dependent manner, with a maximum ROS reduction of 25.7% at 1600 μM in a UV setting. At the same concentration, it can increase cell viability in AAPH-treated cells.

In vivo, Ecamsule is used as a topical sunscreen agent. Studies in human subjects have shown that the systemic absorbed dose of Ecamsule is less than 0.1%, indicating that it is not significantly absorbed through the skin. It remains primarily on the skin surface, providing localized protection against UVA radiation. It has potential for research into conditions like polymorphous light eruption (PMLE).

The in vitro assay for Ecamsule typically involves measuring its ability to absorb UV radiation and protect cells from UV-induced damage. Cells, such as wild-type Fibs E6/E7 cells, are treated with Ecamsule (200-1600 μM) and then exposed to UV radiation. The protective effect is assessed by measuring cell viability, ROS production, or DNA damage markers like pyrimidine dimers.

Cellular assays for Ecamsule are performed using cell lines like Fibs E6/E7 cells. The cells are treated with varying concentrations of Ecamsule (200-1600 μM) and then exposed to UV or AAPH to induce oxidative stress. Cell viability is measured using standard assays, and ROS production is quantified using fluorescent probes. The compound's ability to reduce oxidative damage is determined from dose-response curves.

In vivo animal studies for Ecamsule are not detailed in the available sources. However, human pharmacokinetic studies have been conducted to assess its systemic absorption. These studies involve the topical application of a sunscreen lotion containing radiolabeled Ecamsule to human subjects, followed by the collection of blood, urine, and skin samples to measure the absorbed dose.

Absorption, Distribution and Excretion
Icarus is a topical preparation and should not be absorbed. L'Oréal studies in human subjects have shown that the systemic absorbed dose of [(14)C]-Icarus is less than 0.1%, and under actual exposure conditions, the systemic exposure to this UVA filter is negligible and poses no risk to human health. Icarus is for external use only. Icarus is for external use only and has no volume of distribution. Icarus is for external use only and is not absorbed or metabolized. The potential health risks of UV filters depend on their toxicity and systemic exposure, which in turn depends on the extent to which the topical substance is absorbed into the body through the skin. This study used a mass balance approach to investigate the systemic absorbed dose of [(14)C]-Mexoryl SX((R)) after topical application of a typical sunscreen lotion. In addition, to assess its relevance to in vitro experiments, this study measured the transdermal absorption of the UVA filter through isolated human skin under the same exposure conditions. Four hours after in vivo application, 89-94% of the radioactive material was recovered from the rinse fluid samples. Radioactivity in urine samples was slightly above background levels, with a maximum equivalent to 0.014% of the locally applied dose. No radioactivity was detected in blood and fecal samples collected within 120 hours after application. In vitro experiments showed that [(14)C]-Mexoryl SX remained primarily on the skin surface 24 hours after application. The total amount of drug absorbed in the dermis and receptor fluid within 24 hours, with an average in vitro absorption of 0.16% of the administered dose, was significant. Based on the in vivo pharmacokinetic results, it can be concluded that the systemic absorbed dose of [(14)C]-Mexoryl SX is less than 0.1%. This value is in good agreement with the corresponding in vitro data, which overestimate the in vivo results, consistent with previous observations of other hydrophilic compounds. This study indicates that, under actual exposure conditions, the systemic exposure to this UVA filter in humans is negligible and poses no risk to human health. An in vivo human study using radioactive terephthaloyl dicamphorsulfonic acid (unspecified 14C site) showed that absorption was detectable within 24 hours after exposure to a 0.16% dose, 4 hours later. Metabolites/Metabolites: Isoscopolamine is not absorbed or metabolized. Biological Half-Life: Isoscopolamine is not absorbed; no half-life data have been reported.
Ecamsule has a favorable pharmacokinetic profile for a topical sunscreen agent. It is not significantly absorbed through the skin, with systemic absorption being less than 0.1% of the applied dose. It remains primarily on the skin surface, minimizing systemic exposure. The compound is not metabolized systemically and is considered safe for topical use.

Toxicity Summary
Identification and Uses: Terephthalimide dicamphorsulfonic acid is a solid. It is a broad-spectrum UVA absorber and also has some UVB absorption capacity. It has been tested in animals for UV shielding. Human Studies: No relevant data are available. Animal Studies: In a 90-day repeated oral administration study in rats, no dose-related effect was observed at a dose of 300 mg/kg/day. At a dose of 1000 mg/kg/day, male rats developed hyperphosphatemia at week 4, and female rats showed decreased levels of protein, albumin, and globulin at week 13. There is evidence of some change in thyroid weight in male animals administered terephthalimide dicamphorsulfonic acid, but the validity of this observation is questionable due to the abnormally low thyroid weight in the control group. A follow-up 21-day study using triethanolamine and sodium salts to investigate thyroid metabolism found no treatment-related changes at doses of 305 mg/kg and 444 mg/kg, respectively. Protein Binding Icarus is for topical use only. Non-human Toxicity Values Oral LD50 in rats >1,835 mg/kg Dermal LD50 in rats >1,637 mg/kg
Ecamsule is considered safe and well-tolerated as a topical sunscreen agent. Systemic toxicity is low due to its minimal skin absorption. In vitro, it has been shown to increase cell viability in AAPH-treated cells at high concentrations. The compound is for external use only.

[1]. Contradictory effects of chemical filters in UV/ROS-stressed human keratinocyte and fibroblast cells. ALTEX. 2019;36(2):231-244.

[2]. A new ecamsule-containing SPF 40 sunscreen cream for the prevention of polymorphous light eruption: a double-blind, randomized, controlled study in maximized outdoor conditions. Cutis. 2009 Feb;83(2):95-103.

Ecamsule is a monoterpenoid compound. It is an organic compound added to many sunscreens to filter UVA rays. It is a benzylidene camphor derivative, a class of derivatives known for their excellent photostability. Ecamsule has been approved for use in the United States since 2006, but only at specific concentrations and in a limited number of products manufactured by L'Oréal. The company obtained approval for these products through the New Drug Application process. Indications: For topical application to filter UVA rays. Mechanism of Action: Ecamsule protects against ultraviolet radiation in the wavelength range of 290-400 nm, with optimal protection at 345 nm. Ecamsule is photostable and does not undergo significant degradation upon exposure to light. In mouse studies, it reduced the formation of UV-induced pyrimidine dimers and delayed the development of skin cancer. In vitro studies have shown that osinamine effectively protects against the harmful effects of ultraviolet radiation.

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Therapeutic Use
Ultraviolet Protectant
/EXPL THER/ This study aims to determine, for regulatory purposes, the potential effects of the broad-spectrum UVA absorber Mexoryl SX (which also partially absorbs UVB) on the occurrence and growth of ultraviolet radiation (UVR)-induced skin tumors in mice. Skh-hr1 mice were exposed to simulated sunlight for 40 weeks, 5 days a week. Two control groups received irradiation but no topical application; three groups were treated with sunscreens containing either the UVA absorber Mexoryl SX (5% or 10%) or the UVB-major absorber 2-ethylhexyl-p-methoxycinnamate (2-EHMC, 5%). 2-EHMC was introduced as a control. Sunscreen was applied three days a week before UV exposure and the remaining two days after UV exposure (consistent with a standard design for photocarcinogenic safety testing). Two different UV doses were administered weekly: a lower dose to one group of unprotected animals, a higher dose to another group of unprotected animals, and a higher dose to three animals that received sunscreen. Cumulative tumor incidence, tumor yield, and median latency in both UV control groups showed a UV-dependent response. Neither concentration of Mexoryl SX increased the probability of tumor development; this is consistent with the principles of a safety test, demonstrating its safety for use in sunlight. Although this study was explicitly designed as a safety test, the results also provide some clues to the efficacy of Mexoryl SX in reducing tumor incidence. Topical application of both concentrations of Mexoryl SX delayed the median latency by 6 weeks in the higher UV-exposed control group, while 5% 2-EHMC delayed it by only 2 weeks. Tumor incidence and yield also showed the same efficacy differences between the two sunscreen ingredients. Based on these results, the tumor protective factor (TBF) was calculated, finding that the TBF for both Mexoryl SX formulations was 2.4, while the TBF for the 5% 2-EHMC formulation was 1.3. These findings suggest that Mexoryl SX is effective in preventing UV radiation-induced carcinogenesis. In a previous study on hairless mice, sub-erythema doses of pure UVA radiation were shown to exacerbate several changes observed during normal aging. Our laboratory synthesized a novel sunscreen (a bisbenzylidene camphorsulfonic acid derivative) (λmax: 345 nm, ε: 47,000). We evaluated the protective efficacy of this sunscreen against UV-A photodamage using a mouse model. Three-month-old hairless albino mice were exposed to a sub-erythema dose (35 J/cm²) of UV-A radiation generated by a xenon lamp and filtered through a WG 345 filter for one year. One group of mice received no treatment, while another group received a formulation containing 5% sunscreen before irradiation. At the end of the study, we compared the skin condition of the protected mice with that of the unprotected mice and unexposed control mice at 3 months and 15 months of age. We found that the visible changes induced by UV-A irradiation were primarily skin laxity and wrinkles. Histological and electron microscopic examinations revealed hyperkeratosis, increased elastic fiber density with altered fiber orientation, and increased glycosaminoglycan deposition. Biochemically, total collagen and collagen hydroxylation levels were decreased, while the collagen III/I+III ratio and fibronectin biosynthesis were increased. All these changes could be mitigated or eliminated by sunscreen.
/EXPL THER/ Background/Objective: Ultraviolet (UV) radiation increases skin pigmentation, typically resulting in uniform darkening of the skin. However, it can sometimes lead to hyperpigmentation due to localized hyperpigmentation. Both UVB and UVA rays can induce skin pigmentation. Methods: This study investigated the in vivo protective effect of sunscreens against pigmentation using a standardized sun protection factor (SPF) test. The method included a delayed assessment of UVB and UVA-induced pigmentation. The anti-pigmentation effect was determined by visual evaluation after 7 days of simulated sunlight exposure. This effect was calculated as the ratio of the minimum pigmentation dose on protected skin to the minimum pigmentation dose on unprotected skin. Broad-spectrum UVB/UVA sunscreens Mexoryl SX and Mexoryl XL, as well as the complete formulation, were tested. Results: The anti-pigmentation effect was positively correlated with the concentration of Mexoryl SX. When used in combination with Mexoryl XL, their anti-pigmentation effects were synergistic. When comparing products with the same SPF (same sun protection index) but different UVA protection levels, only sunscreens with high UVA protection levels showed similar effects in both sun protection and anti-pigmentation. Products with low UVA protection levels were less effective at preventing pigmentation compared to their sun protection effect. Conclusion: These studies indicate that SPF values alone are insufficient to explain their effectiveness in preventing pigmentation; UVA protection is an important component in preventing pigmentation.
For more complete data on the therapeutic uses of terephthaloyl dicamphorsulfonic acid (6 types), please visit the HSDB record page.

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Pharmacodynamics
When exposed to ultraviolet light, ezetin undergoes reversible photoisomerization, followed by photoexcitation. The absorbed ultraviolet light is released as heat energy and does not penetrate the skin, thus protecting the skin from ultraviolet radiation.

Ecamsule is a broad-spectrum UVA filter used in sunscreen products to protect against solar radiation. It is photostable and reduces biological damage such as pyrimidine dimer formation and p53 accumulation. The compound has potential for research into polymorphous light eruption (PMLE). It is available from chemical suppliers for research purposes.

C28H34O8S2

562.69476

562.169

92761-26-7

92761-26-7 (free);92841-53-7 (ditriethanolamine)

146382

Solid

1.4±0.1 g/cm3

255° (dec)

1.631

1.35

2

8

6

38

1230

0

O=C1C2(C(C(CC2)C1=CC1C=CC(C=C2C3C(C(CS(O)(=O)=O)(CC3)C2=O)(C)C)=CC=1)(C)C)CS(O)(=O)=O

HEAHZSUCFKFERC-UHFFFAOYSA-N

InChI=1S/C28H34O8S2/c1-25(2)21-9-11-27(25,15-37(31,32)33)23(29)19(21)13-17-5-7-18(8-6-17)14-20-22-10-12-28(24(20)30,26(22,3)4)16-38(34,35)36/h5-8,13-14,21-22H,9-12,15-16H2,1-4H3,(H,31,32,33)(H,34,35,36)

[3-[[4-[[7,7-dimethyl-3-oxo-4-(sulfomethyl)-2-bicyclo[2.2.1]heptanylidene]methyl]phenyl]methylidene]-7,7-dimethyl-2-oxo-1-bicyclo[2.2.1]heptanyl]methanesulfonic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

Ethanol: ~50 mg/mL (~88.9 mM; with ultrasonication)
Methanol: ~31.3 mg/mL (~55.5 mM; with ultrasonication)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.44 mM) (saturation unknown) in 10% EtOH + 40% PEG300 + 5% Tween-80 + 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 ethanol stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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: ≥ 2.5 mg/mL (4.44 mM) (saturation unknown) in 10% EtOH + 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 ethanol stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well.
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.)