Atraric acid
(Synonyms: Methyl atrarate) 目录号 : GC66207
Atraric acid (Methyl atrarate) 是一种特异的雄激素受体 (androgen receptor) 拮抗剂，具有抗炎和抗癌作用。Atraric acid 抑制 LNCaP 和 C4-2 细胞中内源性前列腺特异性抗原基因的表达。Atraric acid 还能抑制 NO 和细胞因子的合成，抑制 MAPK-NFκB 信号通路。Atraric acid 可用于前列腺疾病和炎症性疾病的研究。
Cas No.:4707-47-5
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
Atraric acid (Methyl atrarate) is a specific androgen receptor (AR) antagonist with anti-inflammatory and anticancer effects. Atraric acid represses the expression of the endogenous prostate specific antigen gene in both LNCaP and C4-2 cells. Atraric acid can also inhibit the synthesis of NO and cytokine, and suppress the MAPK-NFκB signaling pathway. Atraric acid can be used to research prostate diseases and inflammatory diseases[1][2].
Atraric acid (10 μM; CV1 cells) represses the transactivation function mediated by Dihydrotestosterone-induced human AR[1].
Atraric acid (10 μM; PCa cells) inhibits the expression of the PSA gene in both androgen-dependent and androgen-independent PCa cells[1].
Atraric acid (1-300 μM; 24 h) dose-dependently inhibits pro-inflammatory cytokine, nitric oxide, prostaglandin E2 in LPS-stimulated RAW264.7 cells, but does not influence the cell viability[2].
Atraric acid (100 and 300 μM; 18 h or 4 h) downregulates the expression of phosphorylated IκB, extracellular signal-regulated kinases (ERK) and nuclear factor kappa B (NFκB) signaling pathway to exhibit anti-inflammatory effects in LPS-stimulated RAW264.7 cells[2].
Cell Viability Assay[2]
| Cell Line: | RAW264.7 cells |
| Concentration: | 1-300 μM |
| Incubation Time: | 24 h |
| Result: | Did not influence the cell viability. |
Western Blot Analysis[2]
| Cell Line: | RAW264.7 cells |
| Concentration: | 100 and 300 μM |
| Incubation Time: | 18 h or 4 h |
| Result: | Inhibited LPS-Induced expression of iNOS and COX-2 in a dose-dependent manner. Suppressed LPS-stimulated phosphorylation of the Nfκb signaling pathway. |
Atraric acid (10, 30 mg/kg; i.p.; single dosage) inhibits the production of pro-inflammatory cytokines and reduces pathological damages in LPS-induced endotoxin shock mice[2].
| Animal Model: | Female BALB/c mice (7 weeks old, 17-20 g; LPS-induced endotoxin shock)[2] |
| Dosage: | 10, 30 mg/kg |
| Administration: | i.p.; single dosage |
| Result: | Inhibited the production of pro-inflammatory cytokines. Reduced pathological damages such as vasodilation and bleeding. |
| Cas No. | 4707-47-5 | SDF | Download SDF |
| 别名 | Methyl atrarate | ||
| 分子式 | C10H12O4 | 分子量 | 196.2 |
| 溶解度 | 储存条件 | 4°C, stored under nitrogen | |
| 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 | 5.0968 mL | 25.4842 mL | 50.9684 mL |
| 5 mM | 1.0194 mL | 5.0968 mL | 10.1937 mL |
| 10 mM | 0.5097 mL | 2.5484 mL | 5.0968 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 | ||||||||||
| 计算重置 | ||||||||||
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。
Atraric acid Ameliorates Hyperpigmentation through the Downregulation of the PKA/CREB/MITF Signaling Pathway
Int J Mol Sci 2022 Dec 15;23(24):15952.PMID:36555593DOI:10.3390/ijms232415952.
Atraric acid (AA) is derived from lichens and is widely used in perfumes for its desirable scent. It has been reported as having anti-inflammatory and antioxidant activity. Hyperpigmentation is the underlying cause of a variety of dermatological diseases that have a significant impact on patients' quality of life and are frequently difficult to treat. This study aimed to explore the inhibitory effects of AA on hyperpigmentation in vitro and in vivo and its potential molecular mechanisms. The cytological results revealed that at a dose of 250 μM, AA may reduce melanin content and tyrosinase levels without causing cytotoxicity. Furthermore, the expression of melanocortin-1 receptor (MC1R), phosphorylated protein kinase A (pPKA) and phosphorylated cAMP response element binding protein (pCREB) were downregulated in AA-administrated cells. In vivo, histological analysis showed that AA could inhibit melanin production and tyrosinase activity, and 3% AA had the best activity, with almost no side effects. Furthermore, the results of Western blot analysis and RT-PCR suggested that AA may suppress the mRNA transcription of microphthalmia-associated transcription factor (MITF) protein and tyrosine protease by decreasing the expression of MC1R, consequently decreasing the phosphorylation of PKA and CREB. Finally, the MC1R inhibitor MSG606 verified the hypothesis that AA suppresses melanin formation by downregulating the PKA/CREB/MITF signaling pathway. Taken together, our study offers valuable information for the development of AA as a possible ingredient in skin-lightening cosmeceuticals and hyperpigmentation inhibitors.
Atraric acid Exhibits Anti-Inflammatory Effect in Lipopolysaccharide-Stimulated RAW264.7 Cells and Mouse Models
Int J Mol Sci 2020 Sep 25;21(19):7070.PMID:32992840DOI:10.3390/ijms21197070.
Lichens, composite organisms resulting from the symbiotic association between the fungi and algae, produce a variety of secondary metabolites that exhibit pharmacological activities. This study aimed to investigate the anti-inflammatory activities of the secondary metabolite Atraric acid produced by Heterodermia hypoleuca. The results confirmed that Atraric acid could regulate induced pro-inflammatory cytokine, nitric oxide, prostaglandin E2, induced nitric oxide synthase and cyclooxygenase-2 enzyme expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Meanwhile, Atraric acid downregulated the expression of phosphorylated IκB, extracellular signal-regulated kinases (ERK) and nuclear factor kappa B (NFκB) signaling pathway to exhibit anti-inflammatory effects in LPS-stimulated RAW264.7 cells. Based on these results, the anti-inflammatory effect of Atraric acid during LPS-induced endotoxin shock in a mouse model was confirmed. In the Atraric acid treated-group, cytokine production was decreased in the peritoneum and serum, and each organ damaged by LPS-stimulation was recovered. These results indicate that Atraric acid has an anti-inflammatory effect, which may be the underlying molecular mechanism involved in the inactivation of the ERK/NFκB signaling pathway, demonstrating its potential therapeutic value for treating inflammatory diseases.
The natural compound Atraric acid suppresses androgen-regulated neo-angiogenesis of castration-resistant prostate cancer through angiopoietin 2
Oncogene 2022 Jun;41(23):3263-3277.PMID:35513564DOI:10.1038/s41388-022-02333-7.
Castration-resistant prostate cancer (CRPC) is an aggressive lethal form of prostate cancer (PCa). Atraric acid (AA) not only inhibits the wild-type androgen receptor (AR) but also those AR mutants that confer therapy resistance to other clinically used AR antagonists, indicating a different mode of AR antagonism. AA induces cellular senescence and inhibits CRPC tumour growth in in vivo xenograft mouse model associated with reduced neo-angiogenesis suggesting the repression of intratumoural neo-angiogenesis by AA. In line with this, the secretome of CRPC cells mediates neo-angiogenesis in an androgen-dependent manner, which is counteracted by AA. This was confirmed by two in vitro models using primary human endothelial cells. Transcriptome sequencing revealed upregulated angiogenic pathways by androgen, being however VEGF-independent, and pointing to the pro-angiogenic factor angiopoietin 2 (ANGPT2) as a key driver of neo-angiogenesis induced by androgens and repressed by AA. In agreement with this, AA treatment of native patient-derived PCa tumour samples ex vivo inhibits ANGPT2 expression. Mechanistically, in addition to AA, immune-depletion of ANGPT2 from secretome or blocking ANGPT2-receptors inhibits androgen-induced angiogenesis. Taken together, we reveal a VEGF-independent ANGPT2-mediated angiogenic pathway that is inhibited by AA leading to repression of androgen-regulated neo-angiogenesis.
The natural compounds Atraric acid and N-butylbenzene-sulfonamide as antagonists of the human androgen receptor and inhibitors of prostate cancer cell growth
Mol Cell Endocrinol 2011 Jan 30;332(1-2):1-8.PMID:20965230DOI:10.1016/j.mce.2010.09.013.
Extracts from the plant Pygeum africanum are widely used in the therapy of benign prostate hyperplasia (BPH) and in combinational therapy for prostate cancer, the second leading cause of cancer death and the mostly diagnosed form of cancer in men. The androgen receptor (AR) plays a crucial role in the development of the prostate as well as in prostate diseases. Even though the extracts from P. africanum are considered as beneficial for prostate diseases in clinical trials, and some active compounds for treatment of BPH could be identified, compounds responsible for AR inhibition and the molecular mechanism for inhibition of prostatitis need to be identified. Recently, Atraric acid and N-butylbenzene-sulfonamide were isolated from a selective dichlormethane extract of P. africanum as two novel AR antagonistic compounds. The molecular mechanisms of AR inhibition were analyzed and are summarized here. Both compounds are the first known natural, complete and specific AR antagonist.
Computational and functional analysis of the androgen receptor antagonist Atraric acid and its derivatives
Anticancer Agents Med Chem 2013 Jun;13(5):801-10.PMID:23194423DOI:10.2174/1871520611313050014.
Androgen receptor (AR) antagonists are important compounds for the treatment of prostate cancer (PCa). The Atraric acid (AA), a natural compound, binds to the AR and acts as a specific AR antagonist. Interestingly, AA represents a novel chemical platform that could serve as a potential basis for new AR antagonists. Therefore, one objective of this study was to analyze the chemical/structural requirements for AR antagonism and to obtain predictions of where and how AA binds to the AR. Further, this study describes the chemical synthesis of 12 AA derivatives and their analysis using a combination of computational and functional assays. Functional analysis of AA derivatives indicated that none activated the AR. Both the para-hydroxyl group and the benzene ortho- and the meta-methyl groups of AA appeared to be essential to antagonize androgen-activated AR activity. Furthermore, extension of the hydrophobic side chain of AA led to slightly stronger AR antagonism. In silico data suggest that modifications to the basic AA structure change the hydrogen-bonding network with the AR ligand binding domain (LBD), so that the para-hydroxyl group of AA forms a hydrogen bond with the LBD, confirming the functional importance of this group for AR antagonism. Moreover, in silico modeling also suggested that the ortho- and meta- methyl groups of AA interact with hydrophobic residues of the ligand pocket of AR, which might explain their functional importance for antagonism. Thus, these studies identify the chemical groups of AA that play key roles in allowing the AA-based chemical platform to act as an AR antagonist.