Peretinoin (NIK333)
(Synonyms: NIK333) 目录号 : GC32107
Peretinoin (NIK333) 是一种具有维生素 A 样结构的口服无环类维生素 A，可靶向类维生素 A 核受体，如类维生素 X 受体 (RXR) 和视黄酸受体 (RAR)。
Cas No.:81485-25-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Peretinoin is an oral acyclic retinoid, inhibits HCV RNA amplification and virus release by altering lipid metabolism.Target: HCVin vitro: Peretinoin is an acyclic retinoid, improves the hepatic gene signature of chronic hepatitis C following curative therapy of hepatocellular carcinoma. Peretinoin is an oral acyclic retinoid with a vitamin A-like structure that targets retinoid nuclear receptors, such as retinoid X receptor and retinoic acid receptor. Peretinoin inhibits HCV RNA amplification and virus release by altering lipid metabolism. Peretinoin suppresses the RNA replication of H77S.3/GLuc2A most efficiently and its EC50 was 9 μM. Peretinoin may reduce the recurrence of hepatocellular carcinoma (HCC) following surgical ablation of primary tumours. Peretinoin inhibits RNA replication for all genotypes and showed the strongest antiviral effect among the retinoids tested. in vivo: In addition, Peretinoin prevents the development of hepatoma in several different hepatoma models.
[1]. Honda M, et al. Peretinoin, an acyclic retinoid, improves the hepatic gene signature of chronic hepatitis C following curative therapy of hepatocellular carcinoma. BMC Cancer. 2013 Apr 15;13:191. [2]. Shimakami T, et al. The acyclic retinoid Peretinoin inhibits hepatitis C virus replication and infectious virus release in vitro. Sci Rep. 2014 Apr 15;4:4688. doi: 10.1038/srep04688.
| Cas No. | 81485-25-8 | SDF | |
| 别名 | NIK333 | ||
| Canonical SMILES | C/C(C)=C/CC/C(C)=C/CC/C(C)=C/C=C/C(C)=C/C(O)=O | ||
| 分子式 | C20H30O2 | 分子量 | 302.45 |
| 溶解度 | DMSO : ≥ 100 mg/mL (330.63 mM) | 储存条件 | Store at -20°C, protect from light, 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 | 3.3063 mL | 16.5317 mL | 33.0633 mL |
| 5 mM | 0.6613 mL | 3.3063 mL | 6.6127 mL |
| 10 mM | 0.3306 mL | 1.6532 mL | 3.3063 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。
Peretinoin as an adjuvant therapy for hepatocellular carcinoma
Expert Rev Gastroenterol Hepatol 2016 Nov;10(11):1201-1210.PMID:27649418DOI:10.1080/17474124.2016.1238303.
The current curative treatment modalities for hepatocellular carcinoma (HCC) are unfortunately fraught with high rates of HCC recurrence. Hence there is a need to prevent or reduce HCC recurrence after initial curative therapy. Peretinoin is a synthetic oral retinoid showing significant reduction in the incidence of recurrent or new HCC in patients who had received curative HCC therapy. Areas covered: Peretinoin is analysed against the background of molecular pathogenesis of the different causes of HCC. Publications related to Peretinoin since 1996 are reviewed, covering clinical characteristics, safety and tolerance profile as well as the current status of clinical development. Expert commentary: Early phase studies are promising but we need to await the results of the ongoing phase III study of Peretinoin in hepatitis C related HCC. Long term impact of Peretinoin may be diminished by the foreseeable near eradication of hepatitis C by the direct acting antivirals.
Peretinoin, an Acyclic Retinoid, for the Secondary Prevention of Hepatocellular Carcinoma
Molecules 2021 Jan 8;26(2):295.PMID:33435572DOI:10.3390/molecules26020295.
The high rates of hepatocellular carcinoma (HCC) recurrence after initially successful curative therapy emphasize ongoing unmet needs to prevent or reduce HCC recurrence. Retinoid acid (RA), a metabolite of vitamin A and its related analogues (termed retinoids) has been suggested as a promising chemotherapeutic agent in cancer treatment. The synthetic oral retinoid Peretinoin is the only agent for the secondary chemoprevention of HCC after curative therapy that is currently well applied into clinical development. Here we present an updated summary of the molecular pathogenesis of HCC and of preclinical and clinical findings with Peretinoin, including its clinical characteristics, safety and tolerability profile and future perspectives for clinical use.
Peretinoin, an Acyclic Retinoid, Inhibits Hepatitis B Virus Replication by Suppressing Sphingosine Metabolic Pathway In Vitro
Int J Mol Sci 2018 Jan 23;19(2):108.PMID:29360739DOI:10.3390/ijms19020108.
Hepatocellular carcinoma (HCC) frequently develops from hepatitis C virus (HCV) and hepatitis B virus (HBV) infection. We previously reported that Peretinoin, an acyclic retinoid, inhibits HCV replication. This study aimed to examine the influence of Peretinoin on the HBV lifecycle. HBV-DNA and covalently closed circular DNA (cccDNA) were evaluated by a qPCR method in HepG2.2.15 cells. Peretinoin significantly reduced the levels of intracellular HBV-DNA, nuclear cccDNA, and HBV transcript at a concentration that did not induce cytotoxicity. Conversely, other retinoids, such as 9-cis, 13-cis retinoic acid (RA), and all-trans-retinoic acid (ATRA), had no effect or rather increased HBV replication. Mechanistically, although Peretinoin increased the expression of HBV-related transcription factors, as observed for other retinoids, Peretinoin enhanced the binding of histone deacetylase 1 (HDAC1) to cccDNA in the nucleus and negatively regulated HBV transcription. Moreover, Peretinoin significantly inhibited the expression of SPHK1, a potential inhibitor of HDAC activity, and might be involved in hepatic inflammation, fibrosis, and HCC. SPHK1 overexpression in cells cancelled the inhibition of HBV replication induced by Peretinoin. This indicates that Peretinoin activates HDAC1 and thereby suppresses HBV replication by inhibiting the sphingosine metabolic pathway. Therefore, Peretinoin may be a novel therapeutic agent for HBV replication and chemoprevention against HCC.
Peretinoin, an acyclic retinoid, inhibits hepatocarcinogenesis by suppressing sphingosine kinase 1 expression in vitro and in vivo
Sci Rep 2017 Dec 5;7(1):16978.PMID:29208982DOI:10.1038/s41598-017-17285-2.
Sphingosine-1-phospate is a potent bioactive lipid metabolite that regulates cancer progression. Because sphingosine kinase 1 and sphingosine kinase 2 (SPHK 1/2) are both essential for sphingosine-1-phospate production, they could be a therapeutic target in various cancers. Peretinoin, an acyclic retinoid, inhibits post-therapeutic recurrence of hepatocellular carcinoma via unclear mechanisms. In this study, we assessed effects of Peretinoin on SPHK expression and liver cancer development in vitro and in vivo. We examined effects of Peretinoin on expression, enzymatic and promoter activity of SPHK1 in a human hepatoma cell line, Huh-7. We also investigated effects of SPHK1 on hepatocarcinogenesis induced by diethylnitrosamine using SPHK1 knockout mice. Peretinoin treatment of Huh-7 cells reduced mRNA levels, protein expression and enzymatic activity of SPHK1. Peretinoin reduced SPHK1 promoter activity; this effect of Peretinoin was blocked by overexpression of Sp1, a transcription factor. Deletion of all Sp1 binding sites within the SPHK1 promoter region abolished SPHK1 promoter activity, suggesting that Peretinoin reduced mRNA levels of SPHK1 via Sp1. Additionally, diethylnitrosamine-induced hepatoma was fewer and less frequent in SPHK1 knockout compared to wild-type mice. Our data showed crucial roles of SPHK1 in hepatocarcinogenesis and suggests that Peretinoin prevents hepatocarcinogenesis by suppressing mRNA levels of SPHK1.
Peretinoin after curative therapy of hepatitis C-related hepatocellular carcinoma: a randomized double-blind placebo-controlled study
J Gastroenterol 2015 Feb;50(2):191-202.PMID:24728665DOI:10.1007/s00535-014-0956-9.
Background: Effective prophylactic therapies have not been established for hepatocellular carcinoma recurrence. Peretinoin represents one novel option for patients with hepatitis C virus-related hepatocellular carcinoma (HCV-HCC), and it was tested in a multicenter, randomized, double-blind, placebo-controlled study. Methods: Patients with curative therapy were assigned to one of the following regimens: Peretinoin 600, 300 mg/day, or placebo for up to 96 weeks. The primary outcome was recurrence-free survival (RFS). Results: Of the 401 patients initially enrolled, 377 patients were analyzed for efficacy. The RFS rates in the 600-mg group, the 300-mg group, and the placebo group were 71.9, 63.6, and 66.0 % at 1 year, and 43.7, 24.9, and 29.3 % at 3 years, respectively. The primary comparison of Peretinoin (300 and 600-mg) with placebo was not significant (P = 0.434). The dose-response relationship based on the hypothesis that "efficacy begins to increase at 600 mg/day" was significant (P = 0.023, multiplicity-adjusted P = 0.048). The hazard ratios for RFS in the 600-mg group vs. the placebo group were 0.73 [95 % confidence interval (CI) 0.51-1.03] for the entire study period and 0.27 (95 % CI 0.07-0.96) after 2 years of the randomization. Common adverse events included ascites, increased blood pressure, headache, presence of urine albumin, and increased transaminases. Conclusions: Although the superiority of Peretinoin to placebo could not be validated, 600 mg/day was shown to be the optimal dose, and treatment may possibly reduce the recurrence of HCV-HCC, particularly after 2 years. The efficacy and safety of Peretinoin 600 mg/day should continue to be evaluated in further studies.