更新于：2024-11-01

Valategrast Hydrochloride

更新于：2024-11-01

概要

研发状态

概要

基本信息

药物类型

合成多肽

别名

Valategrast、Valategrast hydrochloride (USAN)

+ [7]

靶点

α4β1 x α4β7

作用机制

α4β1拮抗剂(整合素α-4/β-1复合体拮抗剂)、α4β7拮抗剂(整合素α-4/β-7复合体拮抗剂)

治疗领域

免疫系统疾病呼吸系统疾病神经系统疾病+ [1]

在研适应症-

非在研适应症

哮喘多发性硬化症

原研机构

F. Hoffmann-La Roche Ltd.

在研机构-

非在研机构

Hoffmann-La Roche, Inc.F. Hoffmann-La Roche Ltd.

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C30H32Cl3N3O4

InChIKeyVZVNFRFMDNFPOM-VWLOTQADSA-N

CAS号220847-86-9

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关联

100 项与 Valategrast Hydrochloride 相关的临床结果

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100 项与 Valategrast Hydrochloride 相关的转化医学

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100 项与 Valategrast Hydrochloride 相关的专利（医药）

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项与 Valategrast Hydrochloride 相关的文献（医药）

2018-12-02·Expert Opinion on Therapeutic Patents2区 · 医学

α₄β₇ integrin inhibitors: a patent review

2区 · 医学

Review

作者: Wei, Ji-Fu ; Gu, Zhi-Chun ; Shi, Fang-Hong ; Huang, Shi-Ying ; Li, Hao ; Zhang, Shun-Guo

INTRODUCTIONThe α₄β₇ integrin is heterodimeric cell surface receptors expressed on most leukocytes. Mucosal addressing cell adhesion molecule 1(MAdCAM-1) is an exclusive ligand for α₄β₇ integrin. Areas covered: This article will highlight the progress that has been made in the discovery and development of α₄β₇ integrin inhibitors, and their use in the treatment of inflammatory bowel diseases, multiple sclerosis, asthma, hepatic disorders, human immunodeficiency virus, allergic conjunctivitis and type 1 diabetes. Expert opinion: α₄β₇ integrin inhibitors have attracted much interest for their clinical implication. Natalizumab and Vedolizumab are monoclonal antibodies (mAbs) successfully utilized clinically. Natalizumab is a mAbs of α₄-subunit blocking both α₄β₁ and α₄β₇ integrin. Vedolizumab selectively targets the α₄β₇ integrin. Several mAbs are still in the process of research and development. Among these mAbs, etrolizumab selectively against the β₇-subunit and AMG-181 specifically against the α₄β₇ integrin are the most promising anti-α₄β₇ integrin antibodies. Despite the unclear development stage of TR-14035 and R411, several low molecular compounds show bright future of further development, such as AJM300 and CDP323. In addition, results from laboratory data show that peptide inhibitors, such as peptide X, are effective α₄β₇ integrin inhibitors.

2014-02-13·ACS Medicinal Chemistry Letters3区 · 医学

Small Macrocycles As Highly Active Integrin α2β1 Antagonists

3区 · 医学

Article

作者: Kohlmann, Markus ; Lindenschmidt, Andreas ; Blum, Horst ; Buning, Christian ; Halland, Nis

Starting from clinical candidates Firategrast, Valategrast, and AJM-300, a series of novel macrocyclic platelet collagen receptor α2β1 antagonists were developed. The amino acid derived low molecular weight 14-18-membered macrocycles turned out to be highly active toward integrin α2β1 with IC50s in the low nanomolar range. The conformation of the macrocycles was found to be highly important for the activity, and an X-ray crystal structure was obtained to clarify this. Subsequent docking into the metal-ion-dependent adhesion site (MIDAS) of a β1 unit revealed a binding model indicating key binding features. Macrocycle 38 was selected for further in vitro and in vivo profiling.

2009-09-01·Drug Development and Industrial Pharmacy4区 · 医学

Functional performance of silicified microcrystalline cellulose versus microcrystalline cellulose: a case study

4区 · 医学

Article

作者: Ashish Chatterji ; Ahmad Aljaberi ; Navnit H. Shah ; Harpreet K. Sandhu

BACKGROUNDDuring the development of a tablet dosage form of an investigational compound, R411, several aspects were identified as critical quality attributes that required optimization. The use of nonsolvent processing prevented the moisture-induced physical changes in the drug product but presented manufacturing challenges related to sticking during compression and slowdown in dissolution after storage at stress conditions.AIMThe aim of this study was to evaluate silicified microcrystalline cellulose (SMCC), microcrystalline cellulose (MCC), and physical mixture of MCC-colloidal silicon dioxide (MCC/CSD at 98:2 ratio) as extragranular compression aids to address the processing and dissolution stability issues of this formulation.METHODSThe compactibility and stickiness upon compression over extended period of time as well as the dissolution of R411 formulations incorporating the aforementioned compression aids were investigated. In addition, the water sorption/desorption properties of these compression aids were determined.RESULTSAll formulations showed comparable compactibility irrespective of the compression aid used. Nevertheless, MCC alone or in a physical mixture with CSD showed sticking of the lower punches, whereas SMCC resulted in clean punch surface during extended compression runs. Furthermore, the three compression aids were compared for their effect on dissolution stability after storage at stress conditions. The formulations containing SMCC provided superior dissolution stability over the other compression aids evaluated in the study.CONCLUSIONSNovel functionalities of SMCC are presented in terms of sticking prevention while having the most beneficial effect on dissolution stability in R411 formulation.

100 项与 Valategrast Hydrochloride 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10028	-	-	-

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
哮喘	临床2期	加拿大	Hoffmann-La Roche, Inc.	2002-10-25
哮喘	临床2期	波多黎各	Hoffmann-La Roche, Inc.	2002-10-25
哮喘	临床2期	澳大利亚	Hoffmann-La Roche, Inc.	2002-10-25
哮喘	临床2期	墨西哥	Hoffmann-La Roche, Inc.	2002-10-25
哮喘	临床2期	美国	Hoffmann-La Roche, Inc.	2002-10-25
多发性硬化症	临床2期	-	F. Hoffmann-La Roche Ltd.	-
多发性硬化症	临床2期	-	F. Hoffmann-La Roche Ltd.	-
多发性硬化症	临床2期	美国	-	-
多发性硬化症	临床2期	美国	-	-