Liarozole dihydrochloride
(Synonyms: R75251 dihydrochloride) 目录号 : GC38554
Liarozole (R75251) dihydrochloride 是一种咪唑衍生物和具有口服活性的视黄酸 (RA) 代谢阻断剂 (RAMBA)。
Cas No.:1883548-96-6
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
| Cell experiment [1]: | |
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Cell lines |
Hepatocellular carcinoma cell line (Huh-7) |
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Preparation Method |
Huh-7 cells were treated with Liarozole for 72 hours, followed by subjecting cell lysates to immunoblotting with Pin1 antibody. |
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Reaction Conditions |
1,5,10,25,50 µM Liarozole for 72 h. |
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Applications |
Liarozole combination with ATRA potently increased the ability of ATRA to induce proline isomerase (Pin1) degradation.Pin1 knockdown suppresses cell proliferation in various human HCC cell lines. |
| Animal experiment [2]: | |
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Animal models |
Sprague-Dawley rats |
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Preparation Method |
Sprague Dawley rats were ovariectomized (OVX) 7 days before the start of the experiment. At 21 days of age the animals were weighed and randomized to treatment groups. Liarozole and vehicle hydroxypropyl-β- cyclodextrin were given twice daily by oral gavage. |
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Dosage form |
20, 80mg/kg Liarozole, oral gavages |
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Applications |
The cumulative tumor growth was significantly slower in Liarozole treatment groups compared to the control group.Liarozole was only able to stop tumor growth. When given in combination, liarozole (80 mg/kg) plus tamoxifen (100 mg/kg) was more effective than liarozole alone. |
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References: [1]. Liao XH, Zhang AL, et al.Chemical or genetic Pin1 inhibition exerts potent anticancer activity against hepatocellular carcinoma by blocking multiple cancer-driving pathways. Sci Rep. 2017 Mar 6;7:43639. [2]. Goss PE, Strasser-Weippl K, et al.Effects of liarozole fumarate (R85246) in combination with tamoxifen on N-methyl-N-nitrosourea (MNU)-induced mammary carcinoma and uterus in the rat model. BMC Cancer. 2007 Jan 31;7:26. |
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Liarozole dihydrochloride is a P-450 inhibitor and retinoic acid (RA) metabolizing blocking agent inhibits RA metabolism and thereby increases intracellular RA levels in cells that actively produce RA. Liarozole has been used in the treatment of a variety of conditions characterized by extracellular matrix (ECM) overproduction such as ichthyosis[1].
IC50 values for P-450 Inhibitors Liarozole was determined as 4.2 μM, using male rat hepatic microsomes and 3uM retinoic acid as substrate[2]. Liarozole combination with ATRA potently increased the ability of ATRA to induce proline isomerase (Pin1) degradation.Pin1 knockdown suppresses cell proliferation in various human HCC cell lines. When the concentration of ATRA was fixed at 10?μM, Pin1 was degraded in a dose dependent manner depending on increasing concentrations of liarozole, with IC50 ~24.5?μM[3]
The cumulative tumor growth was significantly slower in Liarozole compared to the control group (p = 0.0001). Both liarozole and tamoxifen when given alone demonstrated anti-tumor effects. However, while tamoxifen lead to tumor shrinkage, liarozole was only able to stop tumor growth. When given in combination, liarozole (80 mg/kg) plus tamoxifen (100 mg/kg) was more effective than liarozole alone (p = 0.0001). There were no significant differences between the two doses of liarozole either when given alone (p = 0.49) or in combination with tamoxifen (p = 0.8)[4]
References:
[1]. Levy G, Malik M, et al. Liarozole inhibits transforming growth factor-β3--mediated extracellular matrix formation in human three-dimensional leiomyoma cultures. Fertil Steril. 2014 Jul;102(1):272-281.e2.
[2]. Ahmad M. Study on cytochrome p-450 dependent retinoic Acid metabolism and its inhibitors as potential agents for cancer therapy. Sci Pharm. 2011 Oct-Dec;79(4):921-35.
[3]. Liao XH, Zhang AL, et al.Chemical or genetic Pin1 inhibition exerts potent anticancer activity against hepatocellular carcinoma by blocking multiple cancer-driving pathways. Sci Rep. 2017 Mar 6;7:43639.
[4]. Goss PE, Strasser-Weippl K, et al.Effects of liarozole fumarate (R85246) in combination with tamoxifen on N-methyl-N-nitrosourea (MNU)-induced mammary carcinoma and uterus in the rat model. BMC Cancer. 2007 Jan 31;7:26.
Liarozole dihydrochloride 是一种 P-450 抑制剂，视黄酸 (RA) 代谢阻断剂可抑制 RA 代谢，从而增加活跃产生 RA 的细胞中的细胞内 RA 水平。利罗唑已用于治疗多种以细胞外基质 (ECM) 过度生成为特征的病症，例如鱼鳞病[1]。
\nP-450 抑制剂 Liarozole 的IC50 值为 4.2 μM，使用雄性大鼠肝微粒体和 3uM 视黄酸作为底物[2]。 Liarozole 与 ATRA 的组合有效地增加了 ATRA 诱导脯氨酸异构酶 (Pin1) 降解的能力。Pin1 敲低抑制了各种人类 HCC 细胞系中的细胞增殖。当 ATRA 浓度固定在 10μM 时，Pin1 以剂量依赖的方式降解，这取决于利罗唑浓度的增加，IC50 ~24.5μM[3] /p>\n
与对照组相比，利罗唑的累积肿瘤生长显着减慢 (p = 0.0001)。单独给予利罗唑和他莫昔芬均显示出抗肿瘤作用。然而，虽然他莫昔芬导致肿瘤缩小，但利罗唑只能阻止肿瘤生长。联用时，利罗唑 (80 mg/kg) 加他莫昔芬 (100 mg/kg) 比单独使用利罗唑更有效 (p = 0.0001)。无论是单独给药 (p = 0.49) 还是与他莫昔芬联合给药 (p = 0.8)，两种剂量的利罗唑都没有显着差异[4]
| Cas No. | 1883548-96-6 | SDF | |
| 别名 | R75251 dihydrochloride | ||
| Canonical SMILES | ClC1=CC(C(C2=CC=C3N=CNC3=C2)N4C=CN=C4)=CC=C1.[H]Cl.[H]Cl | ||
| 分子式 | C17H15Cl3N4 | 分子量 | 381.69 |
| 溶解度 | Water: ≥ 50 mg/mL (131.00 mM); DMSO: 50 mg/mL (131.00 mM) | 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 | 2.6199 mL | 13.0996 mL | 26.1993 mL |
| 5 mM | 0.524 mL | 2.6199 mL | 5.2399 mL |
| 10 mM | 0.262 mL | 1.31 mL | 2.6199 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。
Gateways to clinical trials
Gateways to Clinical Trials is a guide to the most recent clinical trials reported in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs:[188Re]-HDD; A-179578, adalimumab, AK-602, albumin interferon alfa, alfimeprase, amelubant, anakinra, anti-CD2 MAb, APD-356, aripiprazole, atvogen; Bimatoprost, bimosiamose, BLP-25, brivaracetam; Caspofungin acetate, cilansetron, CMV vaccine (bivalent), conivaptan hydrochloride, Cypher; Darbepoetin alfa, darifenacin hydrobromide, D-D4FC, decitabine, dnaJP1, doranidazole, dronedarone hydrochloride; Efalizumab, efaproxiral sodium, emtricitabine, Endeavor, entecavir, erlotinib hydrochloride, escitalopram oxalate, etoricoxib, etravirine, ezetimibe; Fampridine, fenretinide, ferumoxtran-10, forodesine hydrochloride; Gantacurium chloride, gemi-floxacin mesilate, Glyminox, GW-501516; HBV-ISS, hepavir B, human insulin, HuMax-CD20, hyaluronic acid, HyCAMP; Icatibant, IDEA-070, IGN-311, imatinib mesylate, insulin detemir, insulin glargine, insulin glulisine; Lapatinib, lasofoxifene tartrate, LB-80380, liarozole fumarate, liposome encapsulated doxorubicin, lumiracoxib, LY-570310; MC-1, melatonin, merimepodib, metanicotine, midostaurin; Natalizumab, nicotine conjugate vaccine, NYVAC-HIV C; Patupilone, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pelitinib, Peru-15, pexelizumab, PHP, pimecrolimus, prednisolone sodium metasulfobenzoate; Recombinant alfa1-antitrypsin (AAT), retigabine, rHA influenza vaccine, rifalazil, rofecoxib, rosiglitazone maleate/Metformin hydrochloride, rostaporfin, rosuvastatin calcium, rubitecan; Selenite sodium, semilente insulin, SMP-797, sorafenib; Talampanel, tenofovir disoproxil fumarate, TER-199, tiotropium bromide, torcetrapib, treprostinil sodium, TTA; ValboroPro, valdecoxib, val-mCyd, valtorcitabine dihydrochloride: XP-828L.
Novel nonsteroidal inhibitor of cytochrome P450(17alpha) (17alpha-hydroxylase/C17-20 lyase), YM116, decreased prostatic weights by reducing serum concentrations of testosterone and adrenal androgens in rats
Background: The purpose of this study was to determine the effects of a nonsteroidal C17-20 lyase inhibitor, 2-(1H-imidazol-4-ylmethyl)-9H-carbazole (YM116), on serum concentrations of androgens and ventral prostatic weight in rats.
Methods: Serum concentrations of testosterone and of dehydroepiandrosterone sulfate and prostatic weights were measured in rats treated with YM116.
Results: YM116 inhibited testicular C17-20 lyase competitively (Ki, 0.38 nM), and decreased the serum testosterone concentration in gonadotropin-releasing hormone-treated rats (ED50, 0.7 mg/kg), indicating that YM116 was about 21-24 times more potent than other C17-20 lyase inhibitors such as ketoconazole and liarozole, and was twice as potent as CB7630. YM116 also reduced dehydroepiandrosterone sulfate levels in ACTH-treated castrated rats (ED50, 11 mg/kg). YM116 (40 mg/kg, p.o., for 2 weeks) was almost comparable to bilateral orchiectomy with respect to the time course and magnitude of the reduction in prostatic weight. Each of these two treatments decreased the prostatic weight 3 days following the treatment. Contrarily, leuprolide transiently increased the prostatic weight and then decreased it. YM116 (100 mg/kg) had no effect on the serum cortisol level in guinea pigs, and slightly decreased the serum aldosterone level in rats.
Conclusions: YM116 is a selective C17-20 lyase inhibitor which decreases rat prostatic weight by reducing androgen production in the testes and adrenal glands.