Fenretinide (4-HPR)   中文名称: 维甲酰酚胺

在多种 T-ALL 细胞系中，芬维A胺 (4-HPR) 表现出短期和长期抗癌作用。在 CCRF-CEM 白血病细胞中，芬维A胺以剂量和时间依赖性方式抑制 DES 活性，在此过程中增加内源性细胞 dhCer 水平。在 CCRF-CEM 和 Jurkat 细胞中，芬维A胺 (3 μM) 会导致 dhCer 积聚 [1]。芬维A胺对神经酰胺的抑制作用可保护胰岛素信号传导。当芬维A胺存在时，脂质可以防止胰岛素刺激的葡萄糖吸收减少[2]。当浓度高于 1 µM 时，芬维A胺会降低 OVCAR-5 细胞的存活和增殖；浓度为 10 µM 时，可抑制生长 70-90%。预孵育三天后，芬维A胺 (1 microM) 显着减少 OVCAR-5 入侵。暴露于 1 µM 4-HPR 后，内皮细胞不形成管；相反，它们产生了微小的细胞聚集体[4]。

在喂食高脂肪饮食的雄性 C57Bl/6 小鼠中，芬维A胺 (4-HPR)（10 mg/kg，腹腔注射）选择性地防止神经酰胺的积聚。胰岛素和葡萄糖耐量测试表明，芬维A胺治疗可增加胰岛素敏感性和葡萄糖耐量[2]。在芬维A胺中添加 25 mg/kg 酮康唑会升高 NOD/SCID 小鼠中 4-HPR 的血浆水平 [3]。

Metabolism / Metabolites
Fenretinide has known human metabolites that include (2S,3S,4S,5R)-6-[4-[[(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoyl]amino]phenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid.

[1]. Dihydroceramide accumulation and reactive oxygen species are distinct and nonessential events in 4-HPR-mediated leukemia cell death. Biochemistry and Cell Biology (2012), 90(2), 209-223.

[2]. Fenretinide Prevents Lipid-induced Insulin Resistance by Blocking Ceramide Biosynthesis. Journal of Biological Chemistry (2012), 287(21), 17426-17437.

[3]. Fenretinide metabolism in humans and mice: utilizing pharmacological modulation of its metabolic pathway to increase systemic exposure. Br J Pharmacol. 2011 Jul;163(6):1263-75.

[4]. Action of fenretinide (4-HPR) on ovarian cancer and endothelial cells. Anticancer Res. 2005 Jan-Feb;25(1A):249-53.

4-hydroxyphenyl retinamide is a retinoid obtained by formal condensation of the carboxy group of all-trans retinoic acid and the anilino group of 4-hydroxyaniline. Synthetic retinoid agonist. Antiproliferative, antioxidant and anticancer agent with a long half-life in vivo. Apoptotic effects appear to be mediated by a mechanism distinct from that of 'classical' retinoids. It has a role as an antineoplastic agent and an antioxidant. It is a retinoid and a monocarboxylic acid amide. It is functionally related to an all-trans-retinoic acid.
A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent.
Fenretinide is an orally-active synthetic phenylretinamide analogue of retinol (vitamin A) with potential antineoplastic and chemopreventive activities. Fenretinide binds to and activates retinoic acid receptors (RARs), thereby inducing cell differentiation and apoptosis in some tumor cell types. This agent also inhibits tumor growth by modulating angiogenesis-associated growth factors and their receptors and exhibits retinoid receptor-independent apoptotic properties. (NCI04)
A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent.

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Drug Indication
Investigated for use/treatment in macular degeneration.

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Mechanism of Action
Fenretinide inhibits the growth of several human cancer cell lines, acting through both retinoid-receptor-dependent and retinoid-receptor-independent mechanisms.1In vivo, fenretinide selectively accumulates in breast tissue and is particularly active in inhibiting rat mammary carcinogenesis.1 An important feature of fenretinide is its ability to inhibit cell growth through the induction of apoptosis rather than through differentiation, an effect that is strikingly different from that of vitamin A.1 In contrast to tamoxifen, which inhibits only estrogen receptor (ER)-positive tumors, fenretinide induces apoptosis in both ER-positive and ER-negative breast cancer cell lines.2 All of these properties render fenretinide an attractive candidate for breast cancer chemoprevention.

C26H33NO2

391.5457

391.251

65646-68-6

5288209

Light yellow to yellow solid powder

1.1±0.1 g/cm3

597.6±42.0 °C at 760 mmHg

162-163°C

315.2±27.9 °C

0.0±1.8 mmHg at 25°C

1.607

7.41

49.33

2

2

6

29

726

0

CC1=C(C(CCC1)(C)C)/C=C/C(=C/C=C/C(=C/C(=O)NC2=CC=C(C=C2)O)/C)/C

AKJHMTWEGVYYSE-FXILSDISSA-N

InChI=1S/C26H33NO2/c1-19(11-16-24-21(3)10-7-17-26(24,4)5)8-6-9-20(2)18-25(29)27-22-12-14-23(28)15-13-22/h6,8-9,11-16,18,28H,7,10,17H2,1-5H3,(H,27,29)/b9-6+,16-11+,19-8+,20-18+

(2E,4E,6E,8E)-N-(4-hydroxyphenyl)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenamide

4-HPR McNR-1967 McNR1967 McNR 1967 HPR Fenretinide

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 : ≥ 130 mg/mL (~332.01 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (6.38 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 25.0 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: ≥ 2.5 mg/mL (6.38 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 25.0 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: ≥ 2.5 mg/mL (6.38 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 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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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。