TRITIUM LABELLING OF RETINOIC ACID ANALOG: PSORIASIS & CANCER CHEMOTHERAPY

类视色素如全反式视黄酸（ATRA）， 13-顺式-视黄酸（13-cis-RA）和合成视黄酸（RA） 在介导细胞生长和分化中的类似物已经产生 感兴趣的是它们用于治疗 皮肤病，如牛皮癣和痤疮，以及用于 肿瘤学应用，如化疗和化学预防。 几种类维生素A，其中包括ATRA，13-cis-RA和etretinate， 目前已上市用于治疗皮肤病， 正在进行癌症应用的实验评估。 虽然 这些类维生素A已被证明在治疗 在这些疾病中，它们的毒性限制和/或阻止了它们的 长期使用。 由于最近的发现 关于类维生素A和类维生素A受体的生物学功能， 现在有可能设计具有改善的治疗效果的化合物， 指数。 本项目合成的RA类似物具有较高的生物活性， 视黄酸受体（RAR）和类视色素之间的选择性 X受体（RXR）1. 它已经被用于直接绑定 研究和与3 H 9-cis RA的竞争性结合，产生相似的Kd 9-顺式RA和ATRA的值。 此外，它还被用来阐明 配体结合，RAR/RXR异二聚化， 和视黄酸依赖的转录。 天然配体， 9-顺式-视黄酸，显示出一定的物理和化学不稳定性， 不适合参加捆绑研究项目 这更稳定 类似物将用于高通量结合和反式激活 RXR配体的测定。 1.“ 4-[1-（3，5，5，8，8，-五甲基-5，6，7，8-四氢-2-萘基） 乙烯基苯甲酸（LGD 1069），一种有效的维甲酸X 受体选择性配体”，Zhang，L.;巴迪亚，B。一、Enyeart，D.; Berger，E.M.;迈斯，D.E.;和Boehm，M.; J.标记化合物 放射性药物，36，701（1995）中所述。 用户详情：实验详情：用户 编号：1704 Triation市，州：Wallingford，CT HPLC资金 来源：行业核磁共振收费：$5122.53 4天计划收入： $4872.34 1化合物

The role of retinoids such as all-trans-retinoic acid (ATRA), 13-cis-retinoic acid (13-cis-RA), and synthetic retinoic acid (RA) analogs in mediating cell growth and differentiation has generated interest in their pharmacological utility for treatment of dermatological diseases, such as psoriasis and acne, as well as for oncological applications, such as chemotherapy and chemoprevention. Several retinoids, among them ATRA, 13-cis-RA, and etretinate are currently marketed for treatment of dermatological diseases and are experimentally being evaluated for cancer applications. Although these retinoids have proven therapeutically effective in the treatment of such diseases, their toxicities have limited and/or prevented their use for prolonged periods. As a result of recent discoveries regarding the biological function of retinoids and retinoid receptors, it is now possible to design compounds with improved therapeutic indices. This RA analog synthesized in this project shows high selectivity between the retinoic acid receptors (RAR) and the retinoid X receptors (RXR)1. It has already been used in direct binding studies and competitive binding with 3H 9-cis RA, yielding similar Kd values for 9-cis RA and ATRA. Additionally it was used to elucidate the relationship between ligand binding, RAR/RXR heterodimerization, and retinoic-dependent transcription. The natural ligand, 9-cis-retinoic acid, shows some physical and chemical instability, and is inappropriate for the binding studies program. This more stable analog will be used for high throughput binding and transactivation assays for the RXR ligands. 1."Syntheses of Isotopically Labeled 4-[1-(3,5, 5,8,8, -Pentamethyl-5,6,7, 8-tetrahydro-2-naphthyl) ethenyl] benzoic Acid (LGD1069), A Potent Retinoid X Receptor-Selective Ligand", Zhang, L.; Badea, B. A.; Enyeart, D.; Berger, E.M.; Mais, D.E.; and Boehm, M.; J. Labelled Compd. Radiopharm., 36, 701 (1995). User Details: Experiment Details: User Number: 1704 Tritiation City, State: Wallingford, CT HPLC Funding Source: Industry NMR Charge: $5122.53 4 days Program Income: $4872.34 1 compound