Delving into the Latest Updates on AS-101 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Arsanilic Acid, Ossirene

+ [8]

Target

IL-10R x α4β1 x αvβ3

Mechanism

IL-10R inhibitors(Interleukin 10 receptor inhibitors), α4β1 antagonists(Integrin alpha-4/beta-1 antagonists), αvβ3 antagonists(Integrin alpha-V/beta-3 antagonists)

Therapeutic Areas

Infectious DiseasesSkin and Musculoskeletal DiseasesUrogenital Diseases+ [4]

Active Indication

Condylomata AcuminataNeoplasmsAmyotrophic Lateral Sclerosis

Inactive Indication

Acute Myeloid LeukemiaChemotherapy-induced damageDermatitis, Atopic+ [9]

Originator Organization

BioMAS Ltd.

Active Organization

Bar-Ilan University

BioMAS Ltd.

Inactive Organization

Cassiopea SpA

Feramda Biopharmaceutical

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC6H8AsNO3

InChIKeyXKNKHVGWJDPIRJ-UHFFFAOYSA-N

CAS Registry98-50-0

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.

Start Date01 Aug 2009

Sponsor / Collaborator

BioMAS Ltd.

NCT00927212 / TerminatedPhase 2

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.

Start Date01 Jun 2009

Sponsor / Collaborator

BioMAS Ltd.

100 Clinical Results associated with AS-101

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100 Translational Medicine associated with AS-101

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100 Patents (Medical) associated with AS-101

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146

Literatures (Medical) associated with AS-101

01 Oct 2024·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

Author: 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.

01 Jul 2024·Experimental Eye Research

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

Article

Author: 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.

01 Jul 2024·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

Author: 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 Deals associated with AS-101

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External Link

KEGG	Wiki	ATC	Drug Bank
-	AS-101	-	DB03006

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Condylomata Acuminata	Phase 2	-	BioMAS Ltd.	-
Acute Myeloid Leukemia	Phase 1	IL	BioMAS Ltd.	01 Jan 2015
Myelodysplastic Syndromes	Phase 1	IL	BioMAS Ltd.	01 Jan 2015
Solid tumor	Preclinical	IL	BioMAS Ltd.	01 Aug 2009
Thrombocytopenia	Preclinical	IL	BioMAS Ltd.	01 Aug 2009
Dermatitis, Atopic	Preclinical	IL	BioMAS Ltd.	01 Jun 2009
Psoriasis	Preclinical	IL	BioMAS Ltd.	01 Nov 2008
Chemotherapy-induced damage	Preclinical	IL	BioMAS Ltd.	-
HIV Infections	Preclinical	IL	BioMAS Ltd.	-
Warts	Discovery	IL	BioMAS Ltd.	01 Mar 2012