Ro 41-5253
目录号 : GC66433
Ro 41-5253 是一种具有口服活性的选择性维甲酸受体 RARα 拮抗剂。Ro 41-5253 可以与 RARα 结合而不诱导转录或影响 RAR/RXR 异二聚化和 DNA 结合。Ro 415253 可抑制癌细胞增殖并诱导细胞凋亡 (apoptosis)，具有抗肿瘤活性。
Cas No.:144092-31-9
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
IC50: 60 nM (RARα), 2.4 μM (RARβ), 3.3 μM (RARγ)[3].
Ro 41-5253 is an orally active selective retinoic acid receptor alpha (RARα) antagonist. Ro 41-5253 can bind RARα without inducing transcription or affecting RAR/RXR heterodimerization and DNA binding. Ro 41-5253 can inhibit cancer cell proliferation and induce apoptosis, has antitumor activity[1][2].
Ro 41-5253 (1 nM-10 μM, 10 days) significantly inhibits MCF-7 and ZR 75.1 cell proliferation and induces cell apoptosis in a time and dose-dependent manner[1].
Cell Proliferation Assay[1]
| Cell Line: | Human breast-carcinoma lines MCF-7 and ZR 75.1 |
| Concentration: | 1 nM-10 μM |
| Incubation Time: | 10 days |
| Result: | Inhibited 81% MCF-7 cell growth at 10 μM, 30% cell growth at 1 μM and no significant inhibitory effect at concentrations below 0.1 μM. Inhibited 74% ZR 75.1 cell growth at 10 μM, 63% cell growth at 1 μM and 42% cell growth at 0.1 μM. |
Apoptosis Analysis[1]
| Cell Line: | Human breast-carcinoma lines MCF-7 and ZR 75.1 |
| Concentration: | 1 nM-10 μM |
| Incubation Time: | 10 days |
| Result: | Induced 28.5, 21.6, 16 and 12% of MCF-7 cells apoptosis at 10 μM, 1 μM, 0.1 μM and 0.01 μM respectively on the fourth day while induced 58, 51, 36 and 21% of cells apoptosis at 10 μM, 1 μM, 0.1 μM and 0.01 μM respectively after six days. Induced 80, 65, 43 and 29% of ZR 75.1 cells apoptosis at 10 μM, 1 μM, 0.1 μM and 0.01 μM respectively on the sixth day. |
Ro 41-5253 (oral gavage, 10-600 mg/kg, once a week, 4 weeks) can reduce tumor volume in female athymic Balb/mice transplanted with MCF-7 cell line[2].
| Animal Model: | Six-week-old female athymic Balb/mice transplanted with MCF-7 cell line[2] |
| Dosage: | 10, 30, 100, 300 and 600 mg/kg |
| Administration: | Oral gavage; once a week; 4 weeks |
| Result: | Resulted in a reduction in tumor volume at doses of 10, 30 and 100 mg/kg with no toxic side effects. |
| Cas No. | 144092-31-9 | SDF | Download SDF |
| 分子式 | C28H36O5S | 分子量 | 484.65 |
| 溶解度 | 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 | 2.0633 mL | 10.3167 mL | 20.6334 mL |
| 5 mM | 0.4127 mL | 2.0633 mL | 4.1267 mL |
| 10 mM | 0.2063 mL | 1.0317 mL | 2.0633 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 | ||||||||||
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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。
RARalpha antagonist Ro 41-5253 inhibits proliferation and induces apoptosis in breast-cancer cell lines
Int J Cancer 1998 Sep 25;78(1):86-94.PMID:9724098DOI:10.1002/(sici)1097-0215(19980925)78:1<86::aid-ijc14>3.0.co;2-3.
Ro 41-5253 is a RARalpha-selective antagonist that binds RARalpha but does not induce transcriptional activation and does not influence RAR/RXR heterodimerization and DNA binding. This retinoid inhibits proliferation and induces apoptosis in MCF-7 and ZR-75.1 estrogen-receptor-positive breast-carcinoma cells in a dose-dependent way. The anti-proliferative effect is more evident in ZR-75.1 cells than in MCF-7 cells and is probably mediated by anti-AP1 activity, a mechanism known to be implied in the action of several retinoids. In the induction of apoptosis also ZR-75.1 cells are more sensitive to treatment with Ro 41-5253 than MCF-7 cells. In ZR-75.1 cells an apoptotic/hypodiploid DNA peak is already evident after 2 days of incubation, whereas in MCF-7 cells it appears only after 4 days. The highest percentage of apoptotic cells, for both cell lines, is reached after 6 days of treatment. The apoptosis pathway is p53-independent and bcl-2 downregulation seems to be correlated with an increase in TGF-beta1 protein. The MDA-MB-231 estrogen-receptor-negative cell line is poorly responsive to Ro 41-5253 treatment, both in terms of proliferation inhibition and apoptosis induction. Ro 41-5253 has proliferation-inhibiting and apoptosis-inducing properties that are not mediated by transcriptional activation from retinoic-acid response elements. This retinoid antagonist seems to be a compound that exerts an anti-tumor activity but does not induce the toxic side effects of retinoids and might, therefore, be considered as a candidate for cancer therapy.
Retinoic acid signaling biomarkers after treatment with retinoic acid and retinoic acid receptor alpha antagonist (Ro 41-5253) in canine testis: an in vitro organ culture study
Theriogenology 2013 Jan 1;79(1):10-6.PMID:23102850DOI:10.1016/j.theriogenology.2012.09.001.
Retinoic acid (RA) is an essential component for development and maintenance of the male genital tract and for spermatogenesis. Aldehyde dehydrogenase (ALDH)1, cytochrome P450 (CYP)26b1, RA receptor (RAR)α, cellular RA-binding protein (CRAB)II, and stimulated by RA gene (STRA)8 are involved in synthesis, metabolism signaling pathways, and as downstream effectors of RA. The objective was to elucidate the effects of exogenous RA and a RARα antagonist on gene expression of ALDH1, CYP26b1, RARα, cellular RA-binding protein II, and STRA8 in an in vitro organ culture model of canine testis. Testicular tissues from medium-sized mixed breed dogs (N = 5; age 8 ± 0.17 mo) were subjected to exogenous all trans-RA (final concentrations of 1, 2, and 10 μM, and DMSO as control) for 24 h. Similarly, testicular tissues were treated with Ro 41-5253 (RARα antagonist), at 1, 10, and 50 μM final concentrations (DMSO as control) for 24 h. Exogenous RA or the RARα antagonist decreased (P < 0.05) mRNA abundance of ALDH1 in a dose-dependent manner compared with control. The CRABII mRNA abundance was greater after RA treatment compared with control (P < 0.01), but only 50 μM Ro 41-5253 effectively decreased CRABII mRNA abundance compared with control (P < 0.01). Although RA did not affect RARα mRNA abundance, the RARα antagonist treatment lowered RARα mRNA abundance compared with control (P < 0.05). Abundance of CYP26b1and STRA8 mRNA were greater (P < 0.05) after RA treatment, but lower (P < 0.05) after RARα antagonist treatment compared with control. In conclusion, exogenous RA decreased mRNA abundance of ALDH1 and increased mRNA abundance of RA signaling molecules and its downstream effectors (CYP26b1, CRABII, and STRA8), whereas treatment with a RARα antagonist effectively decreased RARα and RA metabolism molecules and its downstream effectors in canine testis. Perhaps pharmacological intervention via the RA pathway would enable canine male contraception or treatment of testicular pathology.
A widely used retinoic acid receptor antagonist induces peroxisome proliferator-activated receptor-gamma activity
Mol Pharmacol 2007 May;71(5):1251-7.PMID:17290005DOI:10.1124/mol.106.033662.
Nuclear receptors (NRs) are transcription factors whose activity is regulated by the binding of small lipophilic ligands, including hormones, vitamins, and metabolites. Pharmacological NR ligands serve as important therapeutic agents; for example, all-trans retinoic acid, an activating ligand for retinoic acid receptor alpha (RARalpha), is used to treat leukemia. Another RARalpha ligand, (E)-S,S-dioxide-4-(2-(7-(heptyloxy)-3,4-dihydro-4,4-dimethyl-2H-1-benzothiopyran-6-yl)-1-propenyl)-benzoic acid (Ro 41-5253), is a potent antagonist that has been a useful and purportedly specific probe of RARalpha function. Here, we report that Ro 41-5253 also activates the peroxisome proliferator-activated receptor gamma (PPARgamma), a master regulator of adipocyte differentiation and target of widely prescribed antidiabetic thiazolidinediones (TZDs). Ro 41-5253 enhanced differentiation of mouse and human preadipocytes and activated PPARgamma target genes in mature adipocytes. Like the TZDs, Ro 41-5253 also down-regulated PPARgamma protein expression in adipocytes. In addition, Ro 41-5253 activated the PPARgamma-ligand binding domain in transiently transfected HEK293T cells. These effects were not prevented by a potent RARalpha agonist or by depleting cells of RARalpha, indicating that PPARgamma activation was not related to RARalpha antagonism. Indeed, Ro 41-5253 was able to compete with TZD ligands for binding to PPARgamma, suggesting that Ro 41-5253 directly affects PPAR activity. These results vividly demonstrate that pharmacological NR ligands may have "off-target" effects on other NRs. Ro 41-5253 is a PPARgamma agonist as well as an RARalpha antagonist whose pleiotropic effects on NRs may signify a unique spectrum of biological responses.
Retinoids in lung cancer chemoprevention and treatment
Ann Oncol 1999;10 Suppl 5:S95-102.PMID:10582149DOI:10.1093/annonc/10.suppl_5.s95.
In this review, we aim to synthesize the emerging picture of retinoids in lung cancer through a summary of ongoing investigations in biology, chemoprevention and therapy settings, in an attempt to clarify the possible role of these agents in such a disease. Early work in head and neck cancer has evidenced the capability of retinoids to interrupt field carcinogenesis by reversing premalignant lesions and decreasing the incidence of second primary tumors (SPTs). At this time, the completed randomized trials in lung cancer have failed to demonstrate an evident chemopreventive effect of the tested agents on different study end points, although both a marginally significant benefit of retinol palmitate in time-to-development rates for smoke-related SPTs and a potential preventive effect of retinol supplementation against mesothelioma in selected populations of asbestos-exposed workers have been recently reported. Concerning the role of retinoids in lung cancer treatment, a moderate activity of 13-cis-retinoic acid (13cRA) or all-transretinoic acid (ATRA) as single agents has been reported in small series of advanced, mostly pretreated lung cancer patients. More encouraging findings derive from combination studies, in which retinoids, especially ATRA, are added to either alpha-interferon or chemotherapy and radiotherapy. Major recent advances have been made towards the understanding of retinoids mechanisms of action; at this regard, the role of RAR-beta basal or treatment-induced levels seems to be of particular interest as intermediate end point and/or independent prognostic factor, besides their known importance in lung carcinogenesis. Future research for chemopreventive and therapeutic programs with retinoids in lung cancer should be focused on the investigation of new generation compounds with a specificity for individual retinoid nuclear receptors. Such selective molecules may have a greater activity against lung cancer, with a more favourable toxicity profile, as recently suggested by our preliminary data on Ro 41-5253.
Cancer prevention by retinoids and carotenoids: independent action on a common target
Biochim Biophys Acta 2005 May 30;1740(2):170-8.PMID:15949684DOI:10.1016/j.bbadis.2005.01.003.
Virtually all human tumors are deficient in gap junctional communication (GJC) and the restoration of GJC by forced expression of connexins reduces indices of neoplasia. The expression of connexin 43 (Cx43) is upregulated by cancer-preventive retinoids and carotenoids which correlates with the suppression of carcinogen-induced transformation in 10T1/2 cells. However, the molecular mechanism for upregulated expression is poorly understood. The retinoic acid receptor antagonist, Ro 41-5253, suppressed retinoid-induced Cx43 protein expression in 10T1/2 cells and the induction of a Cx43 luciferase reporter construct in F9 cells, but did not suppress protein expression or reporter activity induced by the non-pro-vitamin A carotenoid astaxanthin. In contrast, Cx43 induction by astaxanthin, but not by a RAR-specific retinoid, was inhibited by GW9662, a PPAR-gamma antagonist. Neither compound required protein synthesis for the induction of Cx43 mRNA, nor was the 5.0 h half-life of Cx43 mRNA altered, indicating direct transcriptional activation. The responsive region was found within -158 bp and +209 bp of the transcription start site. Site directed mutagenesis of a GC-box in this region increased basal levels of transcription and loss of retinoid responsiveness. Simultaneous treatment with a retinoid and beta-carotene or astaxanthin resulted in supra-additive Cx43 expression, again indicating separate mechanisms of gene regulation.