Ac-PHSCN-NH2(Ac-PHSCN-NH2) - 药物靶点：α5β1 x αvβ3_专利_临床

概要

基本信息

药物类型

合成多肽

别名

靶点

α5β1 x αvβ3

作用机制

α5β1拮抗剂(整合素α-5/β-1复合体拮抗剂)、αvβ3拮抗剂(整合素α-V/β-3复合体拮抗剂)

治疗领域

肿瘤神经系统疾病泌尿生殖系统疾病

在研适应症-

非在研适应症

晚期肾细胞癌胶质瘤

原研机构

Attenuon, LLC

在研机构-

非在研机构

Attenuon, LLC

Tactic Pharma LLC

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C23H35N9O8S

InChIKeyMMHDBUJXLOFTLC-WOYTXXSLSA-N

CAS号262438-43-7

序列信息

Sequence Code 46185

关联

2

项与 Ac-PHSCN-NH2 相关的临床试验

NCT00352313 / Completed临床1/2期IIT

A Phase I/II Study of ATN-161 and Carboplatin in Adult Patients With Recurrent Intracranial Malignant Glioma

RATIONALE: ATN-161 may stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving ATN-161 together with carboplatin may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of ATN-161 when given together with carboplatin and to see how well they work in treating patients with recurrent malignant glioma.

开始日期2006-05-01

申办/合作机构

National Institutes of Health Clinical Center

[+1]

NCT00131651 / Terminated临床2期

A Dose-Ranging, Phase II, Open Label Study of ATN 161 in Advanced Renal Cell Cancer

The purpose of this study is to determine an active dose of ATN-161 for future studies while establishing preliminary evidence of effectiveness in patients with renal cell cancer.

开始日期2005-08-01

申办/合作机构

Attenuon, LLC

100 项与 Ac-PHSCN-NH2 相关的临床结果

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100 项与 Ac-PHSCN-NH2 相关的转化医学

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100 项与 Ac-PHSCN-NH2 相关的专利（医药）

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51

项与 Ac-PHSCN-NH2 相关的文献（医药）

2024-11-01·Biochemical and Biophysical Research Communications

Unraveling the molecular basis for effective regulation of integrin α5β1 for enhanced therapeutic interventions

Article

作者: Singh, Divya ; Sarangi, Pranita P ; Mishra, Nidhi ; Sarangi, Pranita P. ; Sharma, Prerna ; Kumar, Puneet

Cell attachment to the extracellular matrix significantly impacts the integrity of tissues and human health. The integrin α5β1 is a heterodimer of α5 and β1 subunits and has been identified as a crucial modulator in several human carcinomas. Integrin α5β1 significantly regulates cell proliferation, angiogenesis, inflammation, tumor metastasis, and invasion. This regulatory role of integrin α5β1 in tumor metastasis makes it an appealing target for cancer therapy. The majority of the drugs targeting integrin α5β1 are limited only to clinical trials. In our study, we have performed 94287 compounds screening to determine potential drugs against α5β1 integrin. We have used ATN-161 as a reference and employed combined bioinformatic methodologies, including molecular modelling, virtual screening, MM-GBSA, cell-line cytotoxicity prediction, ADMET, Density Functional Theory (DFT), Non-covalent Interactions (NCI) and molecular simulation, to identify putative integrin α5β1 inhibitors. We found Taxifolin, PD133053, and Acebutolol that possess inhibitory activity against α5β1 integrin and could act as effective drug for the cancer treatment. Taxifolin, PD133053, and Acebutolol exhibited excellent binding to the druggable pocket of integrin α5β1, and also maintained a unique binding mechanism with extra hydrophobic contacts at molecular level. Overall, our study gives new pharmacological candidates that may act as a potential drug against integrin α5β1.

2024-11-01·International Immunopharmacology

Integrin-β1 aggravates paraquat-induced pulmonary fibrosis by activation of FAK/ ERK1/2 pathway depending on fibrotic ECM

Article

作者: Zhang, Ran ; Ma, Yuan ; Tu, Mengyun ; Yang, Jingwen ; Xie, Mengying ; Wang, Zhiyi ; Chen, Chan ; Wang, Liang ; Weng, Jie ; Jin, Haijuan ; Wang, Zhibin

BACKGROUNDIrreversible pulmonary fibrosis induced by paraquat is the most prevalent cause of death in patients with paraquat poisoning. Pulmonary fibrosis is characterized by abnormal deposition of extracellular matrix (ECM). Currently, the role of fibrotic ECM microenvironment in paraquat-induced pulmonary fibrosis has not been established.METHODSRat pulmonary fibrosis model was induced by paraquat, ATN-161 (an integrin-β₁ antagonist) was given to investigate their effect on Rat survival and pulmonary fibrosis. Lungs were decellularized to generate normal and fibrotic acellular ECM scaffolds using Triton and SDS. Fibroblasts were cocultured with ECM scaffolds to established 3D culture systems to investigate the relationship between fibrotic ECM and the differentiation of fibroblasts. Then we explored the effect of fibrotic ECM microenvironment systematically promoting on integrin-β1/FAK/ERK1/2 pathway and established 3D culture systems to investigate the relationship between fibrotic ECM and the differentiation of fibroblasts.RESULTSAntagonism of integrin-β₁ could alleviate paraquat-induced pulmonary fibrosis and ameliorate survival status of rats. Compared to normal ECM, fibrotic extracellular microenvironment promoted the differentiation of fibroblasts to myofibroblasts. Antagonism of integrin-β₁ could also ameliorate the promotion of fibrotic extracellular microenvironment on differentiation of fibroblasts to myofibroblasts. Fibrotic ECM microenvironment promotes fibroblasts transforming into myofibroblasts through integrin-β₁/FAK/ERK1/2 signaling pathway. Moreover, this phenomenon holds independent on exogenous integrin-β₁.CONCLUSIONSActivation of integrin-β₁/FAK/ERK1/2 pathway aggravates paraquat-induced pulmonary fibrosis depend on fibrotic ECM and integrin-β₁ may be a prospective therapeutic target for paraquat-induced pulmonary fibrosis in the future.

2024-10-01·Journal of Genetics and Genomics

ATN-161 alleviates caerulein-induced pancreatitis

Article

作者: Deng, Zhao-hua ; Wang, Yu-xiang ; Zhong, Jing ; Gao, Rong-rong ; Liu, Yang ; Li, Yu-yan ; Ma, Lan-yue ; Chen, Qi ; Wang, Yu-Xiang ; Gao, Rong-Rong ; Chen, Jian-wei ; Zhou, Zi-Yuan ; Shu, Ya-Hai ; Shu, Ya-hai ; Deng, Zhao-Hua ; Ma, Lan-Yue ; Chen, Jian-Wei ; Zhou, Zi-yuan ; Li, Yu-Yan

Pancreatitis is a common gastrointestinal disorder that causes hospitalization with significant morbidity and mortality. The mechanistic pathophysiology of pancreatitis is complicated, limiting the discovery of pharmacological intervention methods. Here, we show that the administration of ATN-161, an antagonist of Integrin-α5, significantly mitigates the pathological condition of acute pancreatitis induced by caerulein. We find that CK19-positive pancreatic ductal cells align parallel to blood vessels in the pancreas. In the caerulein-induced acute pancreatitis model, the newly emergent CK19-positive cells are highly vascularized, with a significant increase in vascular density and endothelial cell number. Single-cell RNA sequencing analysis shows that ductal and endothelial cells are intimate interacting partners, suggesting the existence of a ductal-endothelial interface in the pancreas. Pancreatitis dramatically reduces the crosstalk in the ductal-endothelial interface but promotes the Spp-1/Integrin-α5 signaling. Blocking this signaling with ATN-161 significantly reduces acinar-to-ductal metaplasia, pathological angiogenesis, and restores other abnormal defects induced by caerulein. Our work reveals the therapeutic potential of ATN-161 as an uncharacterized pharmacological method to alleviate the symptoms of pancreatitis.

100 项与 Ac-PHSCN-NH2 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05491

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
晚期肾细胞癌	临床2期	美国	Attenuon, LLC	2005-08-01
胶质瘤	临床2期	-	Attenuon, LLC	-
胶质瘤	临床2期	美国	-	-
胶质瘤	临床2期	-	Tactic Pharma LLC	-