6-[1-(5,6,7,8-四氢-3,5,5,8,8-五甲基-2-萘基)环丙基]-3-吡啶羧酸

用途

LG100268 (LG268) 是一种有效的、选择性的,具有口服活性的视黄素X受体 (RXR) 激动剂,对 RXR-α,RXR-β,和RXR-γ 的 EC50 值分别为 4 nM、3 nM、4 nM。LG100268 显示对 RXR 的选择性优于 RAR (1000 倍), 对 RXR-α,RXR-β,和 RXR-γ 的 Ki 值分别为 3.4 nM,6.2 nM 和 9.2 nM。LG100268 激活 RXR 同源二聚体,诱导转录激活。LG100268 可用于肺癌的研究。

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名称

[ CAS 号 ]:
153559-76-3

[ 中文名 ]:
6-[1-(5,6,7,8-四氢-3,5,5,8,8-戊甲基-2-萘基)氯丙基]-3-吡啶羧酸

[ 英文名 ]:
LG100268

[英文别名 ]:

AmbkkkkK580
BIDD:PXR0022

生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> 自噬 >> 自噬

研究领域 >> 代谢疾病

信号通路 >> 代谢酶/蛋白酶 >> RAR/RXR

[体外研究]

LG100268(100 nM-1μM；24小时)显示RAW264.7细胞中CXCL2和IL-1βmRNA表达下调2.5倍[3]。细胞活力测定[3]细胞系：RAW264.7细胞浓度：100nm-1μM孵育时间：24小时结果：LPS诱导的细胞因子mRNA水平降低。

[体内研究]

LG100268(口服；100mg/kg；每天一次；7周)与C/P联合使用比单独使用LG268或C/P更显著地降低平均肿瘤负荷。与对照组相比,联合用药可减少肺部肿瘤的发生,减少82%(单药组为59%-67%)[3]。动物模型：A/J小鼠[3]剂量：50mg/kg(联合卡铂(50mg/kg i.p.)在LG268治疗饮食后1周开始)给药：口服,每日一次；7周结果：小鼠肺肿瘤生长明显减少。

[参考文献]

[1]. M F Boehm, et al. Design and Synthesis of Potent Retinoid X Receptor Selective Ligands That Induce Apoptosis in Leukemia Cells. J Med Chem

[2]. D S Lala, et al. Activation of Specific RXR Heterodimers by an Antagonist of RXR Homodimers.Nature. 1996 Oct 3;383(6599):450-3.

[3]. Martine Cao,et al.The Rexinoids LG100268 and LG101506 Inhibit Inflammation and Suppress Lung Carcinogenesis in A/J Mice. Cancer Prev Res (Phila). 2016 Jan;9(1):105-14.

物理化学性质

[ 密度 ]:
1.115g/cm3

[ 沸点 ]:
487ºC at 760mmHg

[ 熔点 ]:
275-277ºC

[ 分子式 ]:
C₂₄H₂₉NO₂

[ 分子量 ]:
363.49300

[ 闪点 ]:
248.3ºC

[ 精确质量 ]:
363.22000

[ PSA ]:
50.19000

[ LogP ]:
5.51710

[ 蒸汽压 ]:
0mmHg at 25°C

[ 折射率 ]:
1.577

[ 储存条件 ]:
-20°C

MSDS

详细MSDS(安全技术说明书)

毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: US5921500

CHEMICAL NAME :: 3-Pyridinecarboxylic acid, 6-(1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naph thalenyl) cyclopropyl)-

CAS REGISTRY NUMBER :: 153559-76-3

LAST UPDATED :: 199806

DATA ITEMS CITED :: 1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 21780 ug/kg/3D-I

TOXIC EFFECTS :: Liver - other changes Biochemical - Effect on specific coenzyme - CoA

REFERENCE :: FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 33,264,1996

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安全信息

[ 危险品运输编码 ]:
NONH for all modes of transport

文献

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Research resource: transcriptome profiling of genes regulated by RXR and its permissive and nonpermissive partners in differentiating monocyte-derived dendritic cells.

Mol. Endocrinol. 24 , 2218-2231, (2010)

Retinoid X receptors (RXRs) are heterodimerization partners for many nuclear receptors and also act as homodimers. Heterodimers formed by RXR and a nonpermissive partner, e.g. retinoic acid receptor (...

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