Bexarotene 优先结合并激活 RXR 同工型，对于 RXRα、RXRβ 和 RXRγ 同工型，Kd=14±2 nM、21±4 nM 和 29±7 nM [1]。 Bexarotene 可有效减少白血病 (HL-60) 细胞的增殖。 Bexarotene 在 1 μM 时可抑制 HL-60 细胞增殖 37% [1]。 Bexarotene 作为单药处理细胞，在高剂量下显示出抗增殖作用，IC50 为 40.62±0.45 μM (PC3) 和 50.20±4.10 μM (DU145) [2]。 Bexarotene（20 和 40 μM）和多西紫杉醇（5 和 10 μM）在抑制 PC3 和 DU145 细胞生长方面表现出协同作用 [2]。 Bexarotene（20 和 40 μM）抑制 PC3 和 DU145 细胞中细胞周期蛋白 D1 和细胞周期蛋白 D3 的表达 [2]。

在帕金森病 (PD) 大鼠模型中，贝沙罗汀（1 mg/kg/天）可有效预防行为缺陷和多巴胺神经元变性的发生，从而显着降低血清 T4 和甘油三酯的变化 [1]。贝沙罗汀是一种能有效阻止肺部肿瘤发展和扩散的药物。在所有三种基因型（p53wt/wtK-raswt/wt、p53val135/wtK-raswt/wt 或 p53wt/wtK-rasko/wt）的小鼠中，贝沙罗汀（灌胃法 100mg/kg）抑制肿瘤多样性和肿瘤体积。贝沙罗汀使 p53wt/wtK-rasko/wt 中腺瘤进展为腺癌的速度降低了约 50%。以及 p53wt/wtK-raswt/wt 的小鼠 [3]。

细胞增殖测定[2]
细胞类型：人 PCa 雄激素非依赖性细胞系 PC3 和 DU145
测试浓度：5、10、20、30 , PC3 细胞为 40 μM； DU145 细胞为 1、5、10、20、40 μM。
孵育持续时间：24和48小时
实验结果：证明具有抗增殖作用，IC50分别为40.62±0.45 µM (PC3)和50.20 ±4.10 µM (DU145)。

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细胞活力测定[2]
细胞类型： PC3 和 DU145 细胞
测试浓度： 20 和 40 µM
<孵化持续时间：24或48小时
实验结果：24小时处理后细胞周期蛋白D1和细胞周期蛋白E2减少。治疗 48 小时后，不仅减少了细胞周期蛋白 D1 和细胞周期蛋白 E2 的表达，而且抑制了细胞周期蛋白 B1 和 CDK1 的表达。

Animal/Disease Models: UL53-3 mice (p53wt/wtK-raswt/wt, p53val135/wtK-raswt/wt, or p53wt/wtK-rasko/wt)[3]
Doses: 100 mg/kg
Route of Administration: Gavage with 18 gage of gavage -needle, 0.1 mL per mouse per day, 5 times a week, continued for 12 weeks
Experimental Results: Inhibited both tumor multiplicity and tumor volume in mice of all three genotypes.

Absorption, Distribution and Excretion
Urinary elimination of bexarotene and its known metabolites is a minor excretory pathway (<1% of administered dose).
After oral administration, bexarotene is absorbed with a Tmax of about two hours. ...Studies in patients with advanced malignancies show approximate single dose linearity within the therapeutic range and low accumulation with multiple doses. Plasma bexarotene AUC and Cmax values resulting from a 75 to 300 mg dose were 35% and 48% higher, respectively, after a fat-containing meal than after a glucose solution. Bexarotene is highly bound (>99%) to plasma proteins. The plasma proteins to which bexarotene binds have not been elucidated, and the ability of bexarotene to displace drugs bound to plasma proteins and the ability of drugs to displace bexarotene binding have not been studied.
The renal elimination of bexarotene and its metabolites was examined in patients with Type 2 diabetes mellitus. Neither bexarotene nor its metabolites were excreted in urine in appreciable amounts. Bexarotene is thought to be eliminated primarily through the hepatobiliary system.

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Metabolism / Metabolites
Four bexarotene metabolites have been identified in plasma: 6- and 7-hydroxy-bexarotene and 6- and 7-oxo-bexarotene. In vitro studies suggest that cytochrome P450 3A4 is the major cytochrome P450 responsible for formation of the oxidative metabolites and that the oxidative metabolites may be glucuronidated. The oxidative metabolites are active in in vitro assays of retinoid receptor activation, but the relative contribution of the parent and any metabolites to the efficacy and safety of /bexarotene/ is unknown.
Bexarotene has known human metabolites that include 6-hydroxy-bexarotene, 7-hydroxy-bexarotene, and 7-oxo-bexarotene.

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Biological Half-Life
7 hours
Terminal half-life of bexarotene is about seven hours.

Hepatotoxicity
Serum aminotransferase elevations occur in 5% of patients treated with bexarotene, but the abnormalities are generally mild, transient and not associated with symptoms or jaundice. However, cases of clinically apparent liver injury with jaundice have been reported with bexarotene therapy, some of which were severe and even fatal. Hepatotoxicity appears to be more common with higher doses. The clinical features of the hepatic injury with bexarotene have not been described in any detail and case reports of hepatotoxicity have yet to be published. Nevertheless, the product label mentions hepatotoxicity and recommends prospective monitoring of routine liver tests.
Likelihood score: D (possible but uncommon cause of clinically apparent liver injury).

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Protein Binding
>99%

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Interactions
Because bexarotene is metabolized by cytochrome P450 3A4, ketoconazole, itraconazole, erythromycin, gemfibrozil, grapefruit juice, and other inhibitors of cytochrome P450 3A4 would be expected to lead to an increase in plasma bexarotene concentrations. Furthermore, rifampin, phenytoin, phenobarbital and other inducers of cytochrome P450 3A4 may cause a reduction in plasma bexarotene concentrations.
Concomitant administration of /bexarotene/ capsules and gemfibrozil resulted in substantial increases in plasma concentrations of bexarotene, probably at least partially related to cytochrome P450 3A4 inhibition by gemfibrozil. Under similar conditions, bexarotene concentrations were not affected by concomitant atorvastatin administration. Concomitant administration of gemfibrozil with /bexarotene/ capsules is not recommended.
Based on interim data, concomitant administration of /bexarotene/ capsules and tamoxifen resulted in approximately a 35% decrease in plasma concentrations of tamoxifen, possibly through an induction of cytochrome P450 3A4. Based on this known interaction, bexarotene may theoretically increase the rate of metabolism and reduce plasma concentrations of other substrates metabolized by cytochrome P450 3A4, including oral or other systemic hormonal contraceptives.
Leukopenic and/or thrombocytopenic effects of bexarotene may be increased with concurrent or recent therapy /with blood dycrasia-causing medications/ if these medications cause the same effects; dosage adjustment of the bone marrow depressant, if necessary, should be based on blood counts.
For more Interactions (Complete) data for BEXAROTENE (10 total), please visit the HSDB record page.

[1]. A review of the molecular design and biological activities of RXR agonists. Med Res Rev. 2019 Jul;39(4):1372-1397.

[2]. Synergistic effect of a retinoid X receptor-selective ligand bexarotene and docetaxel in prostate cancer. Onco Targets Ther. 2019 Sep 24;12:7877-7886.

[3]. Prevention of lung cancer progression by bexarotene in mouse models. Oncogene. 2006 Mar 2;25(9):1320-9.

Bexarotene is a retinoid, a member of benzoic acids and a member of naphthalenes. It has a role as an antineoplastic agent.
Bexarotene (Targretin) is an antineoplastic agent indicated by the FDA for Cutaneous T cell lymphoma. It has been used off-label for lung cancer, breast cancer, and Kaposi's sarcoma.
Bexarotene is a Retinoid.
Bexarotene is a retinoid analogue that is used to treat the skin manifestations of cutaneous T cell lymphoma (CTCL). Bexarotene therapy is associated with a high rate of serum enzyme elevations and rare instances of clinically apparent acute liver injury.
Bexarotene is a synthetic retinoic acid agent with potential antineoplastic, chemopreventive, teratogenic and embryotoxic properties. Bexarotene selectively binds to and activates retinoid X receptors (RXRs), thereby inducing changes in gene expression that lead to cell differentiation, decreased cell proliferation, apoptosis of some cancer cell types, and tumor regression. (NCI04)
A rexinoid (an RXR-binding ligand), tetrahydronaphthalene derivative and RETINOID X RECEPTOR antagonist that is used in the treatment of CUTANEOUS T-CELL LYMPHOMA.

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Drug Indication
Used orally for the treatment of skin manifestations of cutaneous T-cell lymphoma (CTCL) in patients who are refractory to at least one prior systemic therapy. Also used topically for the treatment of skin lesions in early (stage IA and IB) CTCL in patients who experience refractory or persistent disease with the use of other therapies or are intolerant of other therapies.
FDA Label
Targretin capsules are indicated for the treatment of skin manifestations of advanced stage cutaneous T-cell lymphoma (CTCL) patients refractory to at least one systemic treatment.

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Mechanism of Action
Bexarotene selectively binds with and activates retinoid X receptor subtypes. There are three subtypes in total: RXR_α, RXR_β, RXR_γ. The exact mechanism of action of bexarotene in the treatment of CTCL is unknown but the drug has activity in all clinical stages of CTCL.
Bexarotene selectively binds and activates retinoid X receptor subtypes (RXR(alpha), RXR(beta), RXR(gamma)). RXRs can form heterodimers with various receptor partners such as retinoic acid receptors (RARs), vitamin D receptor, thyroid receptor, and peroxisome proliferator activator receptors (PPARs). Once activated, these receptors function as transcription factors that regulate the expression of genes that control cellular differentiation and proliferation. Bexarotene inhibits the growth in vitro of some tumor cell lines of hematopoietic and squamous cell origin. It also induces tumor regression in vivo in some animal models. The exact mechanism of action of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL) is unknown.

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Therapeutic Uses
THERAP CAT: Antineoplastic
Bexarotene is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lyphoma in patients who are refractory to at least one other prior systemic therapy. /Included in US product label/

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Drug Warnings
May cause fetal harm; teratogenicity and embryolethality demonstrated in animals. No adequate and well-controlled studies to date in humans. Pregnancy should be avoided during therapy. If used during pregnancy, apprise of potential fetal hazard. ... Male patients receiving the drug should use condoms during sexual intercourse with women who are or may become pregnant.
Effective contraception must be used for one month prior to the initiation of therapy, during therapy and for at least one month following discontinuation of therapy; it is recommended that two reliable forms of contraception be used simultaneously unless abstinence is the chosen method. Bexarotene can potentially induce metabolic enzymes and thereby theoretically reduce the plasma concentrations of oral or other systemic hormonal contraceptives.
Hyperlipidemia occurred in 79% of patients receiving oral bexarotene in phase II-III clinical studies. Elevations in fasting triglycerides and cholesterol and decreases in HDL-cholesterol were observed in more than half of patients receiving 300 mg/sq m or more. Lipid abnormalities usually developed within 2-4 weeks and were reversible with cessation of therapy. If fasting triglycerides are elevated or become elevated during treatment, antilipemic therapy should be instituted, and the dosage of bexarotene reduced or suspended.
Acute pancreatitis has been reported in several patients treated with bexarotene and has been fatal in at least one patient. The manufacturer states that patients with cutaneous T-cell lymphoma (CTCL) who have risk factors for pancreatitis (eg, prior pancreatitis, uncontrolled hyperlipidemia, excessive alcohol consumption, uncontrolled diabetes mellitus, biliary tract disease, or drugs associated with pancreatic toxicity or known to increase triglyceride concentrations) generally should not be treated with bexarotene.
For more Drug Warnings (Complete) data for BEXAROTENE (15 total), please visit the HSDB record page.

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Pharmacodynamics
Bexarotene is a member of a subclass of retinoids that selectively activate retinoid X receptors (RXRs). These retinoid receptors have biologic activity distinct from that of retinoic acid receptors (RARs). Bexarotene is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy. Bexarotene selectively binds and activates retinoid X receptor subtypes (RXR_α, RXR_β, RXR_γ). RXRs can form heterodimers with various receptor partners such as retinoic acid receptors (RARs), vitamin D receptor, thyroid receptor, and peroxisome proliferator activator receptors (PPARs). Once activated, these receptors function as transcription factors that regulate the expression of genes that control cellular differentiation and proliferation. Bexarotene inhibits the growth in vitro of some tumor cell lines of hematopoietic and squamous cell origin. It also induces tumor regression in vivo in some animal models.

C24H28O2

348

348.208

153559-49-0

Bexarotene-d4;2182068-00-2

82146

White to off-white solid powder

1.0±0.1 g/cm3

489.7±44.0 °C at 760 mmHg

230-231ºC

229.5±23.1 °C

0.0±1.3 mmHg at 25°C

1.556

8.55

37.3

1

2

3

26

551

0

NAVMQTYZDKMPEU-UHFFFAOYSA-N

InChI=1S/C24H28O2/c1-15-13-20-21(24(5,6)12-11-23(20,3)4)14-19(15)16(2)17-7-9-18(10-8-17)22(25)26/h7-10,13-14H,2,11-12H2,1,3-6H3,(H,25,26)

4-[1-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)ethenyl]benzoic acid

LGD1069; LGD 1069; LG 100069; Ro26-445; LGD-1069; SR-11247; Ro 26 445; Targretin Ro 26-445; SR 11247; SR11247; 3-methyl TTNEB. Bexarotene; US trade name: Targretin.

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)

配方 1 中的溶解度: 2.62 mg/mL (7.52 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浮液；超声助溶。
*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: 2.62 mg/mL (7.52 mM) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
*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: ≥ 2.08 mg/mL (5.97 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 20.8 mg/mL澄清的DMSO储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入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 4 中的溶解度: ≥ 2.08 mg/mL (5.97 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100μL 20.8mg/mL澄清的DMSO储备液加入到900μL 20％SBE-β-CD生理盐水中，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 5 中的溶解度: ≥ 2.08 mg/mL (5.97 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 20.8 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。