Temarotene (Ro 15-0778)
(Synonyms: 替马罗汀; Ro 15-0778) 目录号 : GC31845
替马罗汀 (Ro 15-0778) 是一种口服给药，特别是类胡萝卜素。
Cas No.:75078-91-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Temarotene is an orally administered, particular arotinoid.
Modulation of ornithine decarboxylase (ODC) gene expression by retinoids is analyzed in human keratinocyte cultures maintained in serum-free medium containing 0.15 mM Ca2+. Cells are incubated with all-trans-retinoic acid, 13-cis-retinoic acid or arotinoid Ro15-0778 (0.1 nM to 10 μM), total RNA is isolated, and mRNA transcripts for ODC are analyzed by Northern and slot blot hybridizations with a human ODC cDNA. Treatment of cells for 24 h results in a dose-dependent decrease in ODC mRNA levels, with an estimated IC50 of approximately 10 nM for all-trans- and 13-cis-retinoic acid, while Ro15-0778 is somewhat less effective (IC50 approximately 0.1-0.5 μM). The suppression of ODC mRNA levels by retinoids is detectable at approximately 3 h of incubation, with essentially a maximal inhibition at 12 h. Reduced ODC mRNA levels noted after 24 h of incubation with 0.5 μM all-trans-retinoic acid are accompanied by a reduction in ODC enzyme activity[1].
The aim of this preliminary report is to measure plasma and skin concentrations of Ro 15-0778 and its phenolic metabolite Ro 14-6113 in hairless rats receiving orally 10 mg/kg of Temarotene once daily during 10 days. Blood (2-3 mL) and skin (200-300 mg) samples are taken at different time points between 0.5 and 240 h after the last dose. A highly sensitive HPLC method is used for simultaneous determination of the two compounds with a quantification limit of 2 ng/mL in plasma and 10 ng/g in total skin (epidermis and dermis). After 10 h, plasma concentrations of Ro 14-6113 are 5-13 times higher than for Ro 15-0778. Ro 14-6113 concentrations in the skin are 4-10 times higher than for Ro 15-0778 within the initial 48 h. The concentrations of both compounds in the skin are higher than concentrations in plasma[1].
[1]. Olsen DR, et al. Suppression of ornithine decarboxylase gene expression by retinoids in cultured human keratinocytes. J Invest Dermatol. 1990 Jan;94(1):33-6. [2]. Fenina N, et al. Concentration of Temarotene (Ro 15-0778) and its metabolite Ro 14-6113 in plasma and skin of hairless rat. Skin Pharmacol. 1993;6(1):61-4.
| Cas No. | 75078-91-0 | SDF | |
| 别名 | 替马罗汀; Ro 15-0778 | ||
| Canonical SMILES | C/C(C1=CC2=C(C(C)(C)CCC2(C)C)C=C1)=C\C3=CC=CC=C3 | ||
| 分子式 | C23H28 | 分子量 | 304.47 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.2844 mL | 16.422 mL | 32.844 mL |
| 5 mM | 0.6569 mL | 3.2844 mL | 6.5688 mL |
| 10 mM | 0.3284 mL | 1.6422 mL | 3.2844 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Concentration of temarotene (Ro 15-0778) and its metabolite Ro 14-6113 in plasma and skin of hairless rat
The aim of this preliminary report was to measure plasma and skin concentrations of Ro 15-0778 and its phenolic metabolite Ro 14-6113 in hairless rats receiving orally 10 mg/kg of Temarotene once daily during 10 days. Blood (2-3 ml) and skin (200-300 mg) samples were taken at different time points between 0.5 and 240 h after the last dose. We used a highly sensitive HPLC method for simultaneous determination of the two compounds with a quantification limit of 2 ng/ml in plasma and 10 ng/g in total skin (epidermis and dermis). After 10 h, plasma concentrations of Ro 14-6113 were 5-13 times higher than for Ro 15-0778. Ro 14-6113 concentrations in the skin were 4-10 times higher than for Ro 15-0778 within the initial 48 h. The concentrations of both compounds in the skin were higher than concentrations in plasma.
Concentrations of isotretinoin and the arotinoid Ro 15-0778 in plasma and tissues of hamsters and rats
The arotinoid Ro 15-0778 is a potent inhibitor of sebum secretion in rodents but not in humans, while isotretinoin (13-cis-retinoic acid, Accutane) inhibits sebum secretion in rodents and humans. The concentrations of Ro 15-0778 and isotretinoin were determined in plasma and target tissues of castrated, testosterone-stimulated hamsters after oral and topical dosing and in castrated, testosterone-stimulated rats after oral dosing. Comparison of this concentration data to that obtained in the plasma and sebum of humans after dosing with Ro 15-0778 and with isotretinoin did not explain why Ro 15-0778 was a potent inhibitor of sebum production in rodents but not in humans.
Therapeutic effect of the arotinoid Ro 15-0778 on chemically induced rat mammary carcinoma
The arotinoid Ro 15-0778 (temarotene) is a third generation retinoid without a polar end-group. Established, palpable and measurable rat mammary tumours, chemically induced by oral administration of 12 mg/animal 7,12-dimethylbenz[a]anthracene, were treated with Ro 15-0778 as a feed-admix in daily doses of 100 mg/kg for 6 weeks and 200 and 400 mg/kg for 9 weeks. For comparison, tamoxifen (anti-oestrogen) was administered as a feed-admix in doses of 10 and 30 mg/kg/day for 9 weeks. Treatment with Ro 15-0778 resulted in a marked retardation of tumour growth in the groups treated with 100 and 200 mg/kg/day and in partial or even complete tumour regression in the group receiving 400 mg/kg/day. Tamoxifen treatment caused a transient tumour growth inhibition during weeks 1-5 with subsequent re-growth of mammary tumours. Both compounds were generally well tolerated. No signs or symptoms of hypervitaminosis A were noted with Ro 15-0778. One single convulsive attack occurred with 200 mg/kg/day of Ro 15-0778 and 400 mg/kg/day caused occasional convulsions in five out of 11 rats. The present investigation underlines the fact that the arotinoid Ro 15-0778 is not only a chemopreventive agent but also exerts a chemotherapeutic effect on established, chemically induced, mammary carcinomas of the rat.
Sebum-suppressing activity of the nonpolar arotinoid Ro 15-0778 in rodents
Retinoids are known to modulate sebaceous gland activity in humans and animals. The nonpolar arotinoid Ro 15-0778 [(E)-1,2,3,4-tetrahydro-1,1,4,4-tetramethyl-6-(1-methyl-2-phenylethen yl) naphthalene] does not contain a polar end group and is devoid of the classical retinoid side effects of hypervitaminosis A. The favorable toxicological profile stimulated the evaluation of this arotinoid in animal models of sebum production. In castrated, testosterone-stimulated male rats, Ro 15-0778 is 50 times more potent than 13-cis-retinoic acid in inhibiting the production and subsequent secretion of sebum. The oral ED50 value of Ro 15-0778 is 30 micrograms/kg, while an oral dose of 0.5 mg/kg inhibited sebum secretion nearly 100%. In testosterone-stimulated female rats, Ro 15-0778 inhibits sebum secretion significantly with an oral ED50 of 140 micrograms/kg and an s.c. ED50 of 75 micrograms/kg. Ro 15-0778 was also evaluated for its ability to prevent testosterone induction of the immature hamster flank organ. The topical ED50 is 0.53 mg/kg and the oral ED50 is 38 mg/kg. This arotinoid is similarly active in mature male hamsters without testosterone treatment. In addition, the retinoid is active topically and orally in reducing the size of the gerbil abdominal sebaceous gland. The compound exhibits no antiandrogenic activity when tested in ventral prostrate and seminal vesicle assays in rats. Additionally, the compound does not have estrogenic activity when tested in the rat uterine weight assay. High doses of Ro 15-0778 in humans did not demonstrate significant sebum-suppressing activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibition of rat mammary carcinogenesis by an arotinoid without a polar end group (Ro 15-0778)
The influence of an arotinoid without a polar end group (Ro 15-0778) on rat mammary carcinogenesis was investigated. Mammary tumors were induced by oral administration of 15 mg, 7,12-dimethylbenz-(a) anthracene (DMBA) to 50-day-old female Sprague-Dawley rats. Ro 15-0778 inhibited the development of mammary adenocarcinomas. The percentage of tumor-bearing rats, the mean number of tumors per rat as well as the mean total volume of tumors per rat were dose-dependently reduced by Ro 15-0778. The results are of particular interest, since this compound--probably because of the lack of a polar end group--does not induce the signs and symptoms of hypervitaminosis A. The inhibition of mammary cancer development by Ro 15-0778 compares favorably with that of N-(4-hydroxyphenyl) retinamide the hitherto most effective retinoid for prevention of chemically-induced mammary cancers in rats.