Fungal squalene epoxidase (inhibitor). [1]

在真菌细胞和细胞提取物中，托萘酯 (NP-27) 抑制甾醇的形成，导致角鲨烯积聚。直接抑制白色念珠菌的微粒体角鲨烯环氧酶[1]证实了这一作用机制。 Tolnaftate (NP-27) 可抑制甾醇的形成，并在 100 µM 剂量下释放高达 30% 的细胞内 [14C]氨基异丁酸 [2]。

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托萘酯 抑制真菌细胞和无细胞提取物中的固醇（麦角固醇）生物合成。
在须癣毛癣菌细胞中，托萘酯 引起 [¹⁴C]醋酸盐掺入固醇的剂量依赖性抑制，并伴随放射性在角鲨烯中的积累。在0.1 mg/L浓度下，它几乎完全阻断了角鲨烯环氧化，96.7%的掺入放射性出现在角鲨烯中。在4-甲基固醇或4,4-二甲基固醇中未观察到积累，排除了对角鲨烯环氧化后步骤的抑制。[1]
在白色念珠菌全细胞中，托萘酯 抑制麦角固醇生物合成，仅引起放射性在角鲨烯中积累。然而，即使在浓度高达100 mg/L时，抑制也不完全。在全细胞中引起50%抑制（IC₅₀）的浓度为0.25 ± 0.05 mg/L，而引起95%抑制的浓度>100 mg/L。[1]
在白色念珠菌的无细胞提取物中，托萘酯 效力更强，抑制麦角固醇生物合成的IC₅₀为0.13 ± 0.03 mg/L，IC₉₅为10.0 ± 1.5 mg/L。[1]
托萘酯 直接抑制来自白色念珠菌的微粒体角鲨烯环氧化酶，IC₅₀为0.32 ± 0.12 mg/L，IC₉₅为12.5 ± 3.8 mg/L。[1]
在白色念珠菌全细胞中，通过 [¹⁴C]醋酸盐掺入测得的抑制效果在pH 4.5时比pH 6.5时弱（例如，在10 mg/L时，分别抑制到对照的16.7% vs 9.7%）。[1]
大鼠肝脏无细胞胆固醇生物合成的敏感性低得多，托萘酯 在100 mg/L时仅引起58.9%的抑制。[1]

使用来自白色念珠菌的微粒体制剂，在可溶性细胞质存在下，检测角鲨烯环氧化酶（EC 1.14.99.7）的活性。
该检测测量角鲨烯转化为角鲨烯环氧化物，这是麦角固醇生物合成的关键步骤。在此无细胞系统中评估了托萘酯和其他化合物对该酶的抑制作用。[1]

通过将细胞（如白色念珠菌、须癣毛癣菌）与放射性前体共孵育来测量真菌细胞中的麦角固醇生物合成。
对于全细胞实验，将细胞与[U-¹⁴C]醋酸盐在pH 6.5下孵育2小时。孵育后，提取不皂化脂质，通过薄层色谱分离，并计数不同组分（如麦角固醇、角鲨烯）中的放射性，以评估生物合成通量和抑制位点。
全细胞中的另一种方法测量了从L-[甲基-¹⁴C]甲硫氨酸通过固醇甲基化反应掺入固醇侧链的放射性，这评估了通路中的后期步骤。
对于无细胞实验，通过掺入[2-¹⁴C]甲羟戊酸（更直接的前体）来测量白色念珠菌细胞提取物中的麦角固醇生物合成。[1]

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Topical tolnaftate has not been studied during breastfeeding and no data are available on the extent of its absorption after topical application. Because it is probably poorly absorbed after topical application, it is considered a low risk to the nursing infant. Avoid application to the nipple area and ensure that the infant's skin does not come into direct contact with the areas of skin that have been treated. Only water-miscible cream, gel or liquid products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking.[1]
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

[1]. Ryder, N.S., I. Frank, and M.C. Dupont, Ergosterol biosynthesis inhibition by the thiocarbamate antifungal agents tolnaftate and tolciclate. Antimicrob Agents Chemother, 1986. 29(5): p. 858-60.

[2]. Georgopapadakou, N.H. and A. Bertasso, Effects of squalene epoxidase inhibitors on Candida albicans. Antimicrob Agents Chemother, 1992. 36(8): p. 1779-81.

Crystals or white powder. (NTP, 1992)
Tolnaftate is a monothiocarbamic ester that is the methyl(3-tolyl)carbamothioate ester of 2-naphthol. A synthetic anti-fungal agent used to treat jock itch, athlete's foot and ringworm. It has a role as an antifungal drug. It is functionally related to a 2-naphthol.
Tolnaftate is a synthetic over-the-counter anti-fungal agent. It may come as a cream, powder, spray, or liquid aerosol, and is used to treat jock itch, athlete's foot and ringworm. It is sold under several brand names, most notably Tinactin and Odor Eaters.
Tolnaftate is a thiocarbamate derivative with either fungicidal or fungistatic property. Tolnaftate is a selective, reversible and non-competitive inhibitor of membrane-bound squalene-2,3- epoxidase, an enzyme involved in the biosynthesis of ergosterol. Inhibition leads to the accumulation of squalene and a deficiency in ergosterol, an essential component of fungal cell walls, thereby increasing membrane permeability, disrupting cellular organization and causing cell death. In addition, this agent may also distort the hyphae and stunts mycelial growth in susceptible fungi.
A synthetic antifungal agent.
See also: TOLNAFTATE; Triclosan (component of).

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Drug Indication
Tolnaftate topical is used to treat skin infections such as athlete's foot, jock itch, and ringworm infections. Tolnaftate is also used, along with other antifungals, to treat infections of the nails, scalp, palms, and soles of the feet. The powder and powder aerosol may be used to prevent athlete's foot.

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Mechanism of Action
Tolnaftate is a topical fungicide. Though its exact mechanism unknown, it is believed to prevent ergosterol biosynthesis by inhibiting squalene epoxidase. It has also been reported to distort the hyphae and to stunt mycelial growth in susceptible organisms.

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Pharmacodynamics
Tolnaftate is a synthetic over-the-counter anti-fungal agent.

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Tolnaftate (O-2-naphthyl-m,N-dimethylthiocarbanilate) is a thiocarbamate antifungal agent.
It is selectively active against dermatophytes and is used clinically as a topical treatment for dermatophyte infections.
Its primary mode of action is the inhibition of fungal squalene epoxidase, a key enzyme in ergosterol biosynthesis, leading to squalene accumulation and ergosterol depletion. This mechanism is similar to that of the allylamine antifungals (e.g., terbinafine).
The good correlation between its antifungal activity and ergosterol biosynthesis inhibition strongly suggests this is its primary mode of action. However, the existence of other mechanisms cannot be ruled out. [1]

C19H17NOS

307.41

307.103

2398-96-1

Tolnaftate-d7;1329835-64-4

5510

White to off-white solid powder

1.2±0.1 g/cm3

453.4±38.0 °C at 760 mmHg

110.5-111.5ºC

228.0±26.8 °C

0.0±1.1 mmHg at 25°C

1.697

5.15

44.56

0

2

3

22

386

0

FUSNMLFNXJSCDI-UHFFFAOYSA-N

InChI=1S/C19H17NOS/c1-14-6-5-9-17(12-14)20(2)19(22)21-18-11-10-15-7-3-4-8-16(15)13-18/h3-13H,1-2H3

O-naphthalen-2-yl N-methyl-N-(3-methylphenyl)carbamothioate

Tinactin, Tinaderm, Aftate; NP-27, NP 27, NP27

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)

DMSO : ~50 mg/mL (~162.65 mM)
H2O : < 0.1 mg/mL

配方 1 中的溶解度: ≥ 3.25 mg/mL (10.57 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 32.5 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 3.25 mg/mL (10.57 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 32.5 mg/mL 澄清 DMSO 储备液加入 900 μL 20% SBE-β-CD 生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 3.25 mg/mL (10.57 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 32.5 mg/mL 澄清 DMSO 储备液加入900 μL 玉米油中，混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。