AS-101(AS-101) - 药物靶点：IL-10R x α4β1 x αvβ3_在研适应症：尖锐湿疣，肿瘤，肌萎缩侧索硬化_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Arsanilic Acid、Ossirene

+ [8]

靶点

IL-10R x α4β1 x αvβ3

作用机制

IL-10R抑制剂(白细胞介素10受体抑制剂)、α4β1拮抗剂(整合素α-4/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

感染皮肤和肌肉骨骼疾病泌尿生殖系统疾病+ [4]

在研适应症

尖锐湿疣肿瘤肌萎缩侧索硬化

非在研适应症

急性髓性白血病化疗引起的损伤特应性皮炎+ [9]

原研机构

在研机构

非在研机构

Feramda Biopharmaceutical

最高研发阶段临床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C6H8AsNO3

InChIKeyXKNKHVGWJDPIRJ-UHFFFAOYSA-N

CAS号98-50-0

关联

10

项与 AS-101 相关的临床试验

NCT01010373 / Suspended临床2期

Application of AS101 in Combination With Chemotherapy for Elderly Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)

The purpose of this study is to determine whether addition of AS101 to the standard chemotherapy regimen is effective in the treatment of newly diagnosed elderly (≥60) AML patients and AML transformed myelodysplastic syndrome (MDS) patients.

开始日期2015-01-01

申办/合作机构

BioMAS Ltd.

NCT00926354 / Terminated临床2期

Phase II Open Study to Evaluate Safety and Efficacy of AS101 for the Treatment of Thrombocytopenia in Solid Tumor

Chemotherapy Induced Thrombocytopenia is a common side-effect of bone marrow suppression as a result of a chemotherapy treatment. AS101 is a tellurium based small compound with immunomodulating characteristics which attributed to the direct inhibition of the anti-inflammatory cytokine IL-10. AS101 was previously shown to induce a significant reduction in thrombocytopenia that accompany cancer therapy with no major toxicity . This phase II randomized open study will evaluate the efficacy of AS101 for the treatment of chemotherapy induced thrombocytopenia in patients with various solid tumors.

开始日期2009-08-01

申办/合作机构

BioMAS Ltd.

NCT00927212 / Terminated临床2期

Randomized Double Blind Uncontrolled Pilot Study to Compare 2% and 4% AS101 Ointment for the Treatment of Atopic Dermatitis

Atopic Dermatitis is a chronic non contagious disease that causes itchy, inflamed skin. The purpose of this study is to evaluate the safety and efficacy of topical AS101 ointment for the treatment of Atopic dermatitis.

开始日期2009-06-01

申办/合作机构

BioMAS Ltd.

100 项与 AS-101 相关的临床结果

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100 项与 AS-101 相关的转化医学

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100 项与 AS-101 相关的专利（医药）

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146

项与 AS-101 相关的文献（医药）

2024-10-01·International Journal of Antimicrobial Agents

Immunomodulator AS101 restores colistin susceptibility of clinical colistin-resistant Escherichia coli and Klebsiella pneumoniae in vitro and in vivo

Article

作者: Gong, Yanchun ; Liu, Haifeng ; Zhou, Tieli ; Zhong, Zeyong ; Chen, Lijiang ; Zhang, Yichi ; Zhang, Ying ; Yang, Yuhan ; Yu, Pingting

OBJECTIVESColistin (COL) was once considered to be the last line of defence against multidrug-resistant bacteria belonging to the family Enterobacteriaceae. Due to the misuse of COL, COL-resistant (COL-R) Enterobacteriaceae have emerged. To address this clinical issue and combat COL resistance, novel approaches are urgently needed.METHODSIn this study, the in vitro and in vivo antimicrobial and antibiofilm effects of the immunomodulator AS101 were investigated in combination with COL against COL-R Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae).RESULTSCheckerboard assay, time-kill assay, and scanning electron microscopy confirmed the in vitro antimicrobial phenotype, whereas, crystal violet staining and multidimensional confocal laser scanning microscopy with live/dead staining confirmed the antibiofilm capability of the combination therapy. Moreover, the Galleria mellonella infection model and the mouse infection model indicated the high in vivo efficacy of the combination therapy. Additionally, cytotoxicity experiments performed using human kidney-derived HK-2 cells and haemolysis assays performed using human erythrocytes collectively demonstrated safety at effective combination concentrations. Furthermore, quantification of the expression of inflammatory cytokines via enzyme-linked immunosorbent assay confirmed the anti-inflammatory advantage of combination therapy. At the mechanistic level, changes in outer and inner membrane permeability and accumulation of ROS levels, which might be potential mechanisms for synergistic antimicrobial effects.CONCLUSIONSThis study found that AS101 can restore COL susceptibility in clinical COL-R E. coli and K. pneumoniae and also has synergistic antibiofilm and anti-inflammatory capabilities. This study provided a novel strategy to combat clinical infections caused by COL-R E. coli and K. pneumoniae.

2024-07-01·Experimental Eye Research

AS101 regulates the Teff/Treg balance to alleviate rabbit autoimmune dacryoadenitis through modulating NFATc2

Article

作者: Yang, Jun ; Wang, Jiali ; Nian, Hong ; Liu, Lin ; Zhang, Jiawen ; Sun, Deming ; Wei, Ruihua ; Wei, Yankai ; Li, Na ; Wang, Xiu

Sjögren's syndrome (SS) dry eye can cause ocular surface inflammation and lacrimal gland (LG) damage, leading to discomfort and potential vision problems. The existing treatment options for SS dry eye are currently constrained. We investigated the possible therapeutic effect and the underlying mechanism of AS101 in autoimmune dry eye. AS101 was injected subconjunctivally into a rabbit model of autoimmune dacryoadenitis and its therapeutic effects were determined by evaluating clinical and histological scores. The expressions of effector T cells (Teff)/regulatory T cells (Treg)-related transcription factors and cytokines, inflammation mediators, and transcription factor NFATc2 were measured by quantitative real-time PCR and/or Western blot both in vivo and in vitro. Additionally, the role of NFATc2 in the immunomodulatory effects of AS101 on T cells was explored by co-culturing activated peripheral blood lymphocytes (PBLs) transfected with NFATc2 overexpression lentiviral plasmid with AS101. AS101 treatment potently ameliorated the clinical severity and reduced the inflammation of LG. Further investigation revealed that AS101 treatment led to decreased expression of Th1-related genes (T-bet and IFN-γ) and Th17-related genes (RORC, IL-17A, IL-17F, and GM-CSF) and increased expression of Treg-related gene Foxp3 in vivo and in vitro. Meanwhile, AS101 suppressed the expression of TNF-α, IL-1β, IL-23, IL-6, MMP-2, and MMP-9. Mechanistically, AS101 downregulated the expression of NFATc2 in inflamed LGs. Overexpression of NFATc2 in activated PBLs partially blunted the effect of AS101 on Teff suppression and Treg promotion. In conclusion, AS101 is a potential regulator of Teff/Treg cell balance and could be an effective treatment agent for SS dry eye.

2024-07-01·Journal of Inorganic Biochemistry

Unveiling the mechanism of activation of the Te(IV) prodrug AS101. New chemical insights towards a better understanding of its medicinal properties

Article

作者: Tolbatov, Iogann ; La Mendola, Diego ; Marrone, Alessandro ; Biver, Tarita ; Chiaverini, Lorenzo ; Marzo, Tiziano

AS101 (Ammonium trichloro (dioxoethylene-O,O') tellurate) is an important hypervalent Te-based prodrug. Recently, we started a systematic investigation on AS101 with the aim to correlate its promising biological effects as a potent immunomodulator drug with multiple medicinal applications and its specific chemical properties. To date, a substantial agreement on the rapid conversion of the initial AS101 species into the corresponding TeOCl₃^- anion does exist, and this latter species is reputed as the pharmacologically active one. However, we realized that TeOCl₃^- could quickly undergo further steps of conversion in an aqueous medium, eventually producing the TeO₂ species. Using a mixed experimental and theoretical investigation approach, we characterized the conversion process leading to TeO₂ occurring both in pure water and in reference buffers at physiological-like pH. Our findings may offer a valuable "chemical tool" for a better description, interpretation -and optimization- of the mechanism of action of AS101 and Te-based compounds. This might be a starting point for improved AS101-based medicinal application.

100 项与 AS-101 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	AS-101	-	DB03006

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
尖锐湿疣	临床2期	-	BioMAS Ltd.	-
急性髓性白血病	临床1期	以色列	BioMAS Ltd.	2015-01-01
骨髓增生异常综合征	临床1期	以色列	BioMAS Ltd.	2015-01-01
实体瘤	临床前	以色列	BioMAS Ltd.	2009-08-01
血小板减少症	临床前	以色列	BioMAS Ltd.	2009-08-01
特应性皮炎	临床前	以色列	BioMAS Ltd.	2009-06-01
银屑病	临床前	以色列	BioMAS Ltd.	2008-11-01
化疗引起的损伤	临床前	以色列	BioMAS Ltd.	-
HIV感染	临床前	以色列	BioMAS Ltd.	-
疣	药物发现	以色列	BioMAS Ltd.	2012-03-01