利阿唑(Liarozole) - 药物靶点：aromatase_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Liazal

靶点

aromatase

作用机制

aromatase调节剂(芳香酶调节剂)

治疗领域

肿瘤泌尿生殖系统疾病遗传病与畸形+ [2]

在研适应症-

非在研适应症

板层状鳞癣前列腺癌

原研机构

Janssen Global Services LLC

在研机构-

非在研机构

Stiefel Laboratories, Inc.

最高研发阶段终止申请上市

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

结构

分子式C17H13ClN4

InChIKeyUGFHIPBXIWJXNA-UHFFFAOYSA-N

CAS号115575-11-6

关联

3

项与利阿唑相关的临床试验

EUCTR2005-000842-35-IT / Not yet recruitingN/A

A Randomised, Double-Blind, Multinational, Multicenter, Placebo-controlled Parallel Phase II/III Trial to Evaluate the Efficacy and Safety of 2 Doses of Oral Liarozole (75 mg o.d. and 150 mg o.d.) Given During 12 weeks in Comparison with Placebo in the Treatment of Subjects with Lamellar Ichthyosis

开始日期2006-11-13

申办/合作机构

Barrier Therapeutics, Inc.

EUCTR2005-000842-35-BE / Not yet recruitingN/A

A randomized, double-blind, multinational, multicenter, placebo-controlled parallel phase II/III trial to evaluate the efficacy and safety of 2 doses of oral liarozole (75 mg o.d. and 150 mg o.d.) given during 12 weeks in comparison with placebo in the treatment of subjects with lamellar ichthyosis. - Efficacy and safety of two doses of liarozole vs. placebo for the treatment of lamellar ichthyosis.

开始日期2006-09-08

申办/合作机构

Barrier Therapeutics, Inc.

NCT00282724 / Completed临床2/3期

A Randomized, Double-blind, Placebo-controlled Phase II/III Trial to Evaluate the Efficacy and Safety of 2 Doses of Oral Liarozole (75 mg od and 150 mg od) Given During 12 Weeks in Lamellar Ichthyosis

Lamellar ichthyosis is a congenital disease of the skin with a generalized scaling. The primary activity of liarozole is considered to be the inhibition of the degradation of a substance called retinoic acid, which is the principal endogenous regulator of growth and differentiation of epithelial tissues in mammals. The current study intends to evaluate the efficacy and safety in patients with lamellar ichthyosis.

开始日期2006-01-01

申办/合作机构

Stiefel Laboratories, Inc.

100 项与利阿唑相关的临床结果

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100 项与利阿唑相关的转化医学

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100 项与利阿唑相关的专利（医药）

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101

项与利阿唑相关的文献（医药）

2024-09-02·Current Topics in Medicinal Chemistry

Recent Advances in Nanocatalyzed One-Pot Sustainable Synthesis of Bioactive N, N-Heterocycles with Anticancer Activities: An Outlook of Medicinal Chemistry

Article

作者: Majhi, Sasadhar

N-heterocycles represent a predominant and unique class of organic chemistry. They have received a lot of attention due to their important chemical, biomedical, and industrial uses. Food and Drug Administration (FDA) approved about 75% of drugs containing N-based heterocycles, which are currently available in the market. N-Heterocyclic compounds exist as the backbone of numerous natural products and act as crucial intermediates for the construction of pharmaceuticals, veterinary items, and agrochemicals frequently. Among N-based heterocyclic compounds, bioactive N,N-heterocycles constitute a broad spectrum of applications in modern drug discovery and development processes. Cefozopran (antibiotic), omeprazole (antiulcer), enviradine (antiviral), liarozole (anticancer), etc., are important drugs containing N,N-heterocycles. The synthesis of N,Nheterocyclic compounds under sustainable conditions is one of the most active fields because of their significant physiological and biological properties as well as synthetic utility. Current research is demanding the development of greener, cheaper, and milder protocols for the synthesis of N,N-heterocyclic compounds to save mother nature by avoiding toxic metal catalysts, extensive application of energy, and the excessive use of hazardous materials. Nanocatalysts play a profound role in sustainable synthesis because of their larger surface area, tiny size, and minimum energy; they are eco-friendly and safe, and they provide higher yields with selectivity in comparison to conventional catalysts. It is increasingly demanding research to design and synthesize novel bioactive compounds that may help to combat cancer since the major causes of death worldwide are due to cancer. Hence, the important uses of nanocatalysts for the one-pot synthesis of biologically potent N,N-heterocycles with anticancer activities have been presented in this review.

2024-05-01·Toxicology and Applied Pharmacology

In silico and in vitro assessment of drugs potentially causing adverse effects by inhibiting CYP17A1

Article

作者: Naeem, Sadaf ; Odermatt, Alex ; Jäger, Marie-Christin ; Smieško, Martin ; Kędzierski, Jacek

Cytochrome P450 enzymes (CYPs) play a crucial role in the metabolism and synthesis of various compound classes. While drug-metabolizing CYP enzymes are frequently investigated as anti-targets, the inhibition of CYP enzymes involved in adrenal steroidogenesis is not well studied. The steroidogenic enzyme CYP17A1 is a dual-function enzyme catalyzing hydroxylase and lyase reactions relevant for the biosynthesis of adrenal glucocorticoids and androgens. Inhibition of CYP17A1-hydroxylase leads to pseudohyperaldosteronism with subsequent excessive mineralocorticoid receptor activation, hypertension and hypokalemia. In contrast, specific inhibition of the lyase function might be beneficial for the treatment of prostate cancer by decreasing adrenal androgen levels. This study combined in silico and in vitro methods to identify drugs inhibiting CYP17A1. The most potent CYP17A1 inhibitors identified are serdemetan, mocetinostat, nolatrexed, liarozole, and talarozole. While some of these drugs are currently under investigation for the treatment of various cancers, their potential for the treatment of prostate cancer is yet to be explored. The DrugBank database was screened for CYP17A1 inhibitors, to increase the awareness for the risk of drug-induced pseudohyperaldosteronism and to highlight drugs so far unknown for their potential to cause side effects resulting from CYP17A1 inhibition.

2021-01-01·Journal of Investigative Dermatology1区 · 医学

Characterization of CYP26B1-Selective Inhibitor, DX314, as a Potential Therapeutic for Keratinization Disorders

1区 · 医学

Review

作者: Liu, Haoming ; Poumay, Yves ; Bourlond, Florence ; Diaz, Philippe ; Balau, Benoît ; Paller, Amy S ; De Glas, Valérie ; Veit, Joachim G S

Inhibition of CYP450-mediated retinoic acid (RA) metabolism by RA metabolism blocking agents increases endogenous retinoids and is an alternative to retinoid therapy. Currently available RA metabolism blocking agents (i.e., liarozole and talarozole) tend to have fewer adverse effects than traditional retinoids but lack target specificity. Substrate-based inhibitor DX314 has enhanced selectivity for RA-metabolizing enzyme CYP26B1 and may offer an improved treatment option for keratinization disorders such as congenital ichthyosis and Darier disease. In this study, we used RT-qPCR, RNA sequencing, pathway, upstream regulator, and histological analyses to demonstrate that DX314 can potentiate the effects of all-trans-RA in healthy and diseased reconstructed human epidermis. We unexpectedly discovered that DX314, but not all-trans-RA or previous RA metabolism blocking agents, appears to protect epidermal barrier integrity. In addition, DX314-induced keratinization and epidermal proliferation effects are observed in a rhino mice model. Altogether, the results indicate that DX314 inhibits all-trans-RA metabolism with minimal off-target activity and shows therapeutic similarity to topical retinoids in vitro and in vivo. Findings of a barrier-protecting effect require further mechanistic study but may lead to a unique strategy in barrier-reinforcing therapies. DX314 is a promising candidate compound for further study and development in the context of keratinization disorders.

100 项与利阿唑相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	利阿唑	-	DB13066

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
板层状鳞癣	申请上市	意大利	Stiefel Laboratories, Inc.	2006-01-01
板层状鳞癣	申请上市	比利时	Stiefel Laboratories, Inc.	2006-01-01
板层状鳞癣	申请上市	荷兰	Stiefel Laboratories, Inc.	2006-01-01
板层状鳞癣	申请上市	德国	Stiefel Laboratories, Inc.	2006-01-01
板层状鳞癣	申请上市	瑞典	Stiefel Laboratories, Inc.	2006-01-01
板层状鳞癣	申请上市	挪威	Stiefel Laboratories, Inc.	2006-01-01
板层状鳞癣	申请上市	法国	Stiefel Laboratories, Inc.	2006-01-01
板层状鳞癣	申请上市	加拿大	Stiefel Laboratories, Inc.	2006-01-01
前列腺癌	申请上市	美国	-	-
板层状鳞癣	药物发现	多米尼加共和国	Stiefel Laboratories, Inc.	2006-01-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00282724 (Pubmed \| Br J Dermatol)	临床2/3期	板层状鳞癣	98	Oral liarozole 75 mg	(衊憲鏇選鬱築蓋繭願窪) = 糧網齋膚廠網遞鹽願夢齋鬱蓋鹹獵鬱淵製蓋觸 (窪壓窪膚襯醖鑰壓膚鏇 )	积极	2014-01-01
				Oral liarozole 150 mg	(衊憲鏇選鬱築蓋繭願窪) = 醖壓餘製鹽簾鬱顧衊構齋鬱蓋鹹獵鬱淵製蓋觸 (窪壓窪膚襯醖鑰壓膚鏇 )