Delving into the Latest Updates on AG-011 with Synapse

Overview

Basic Info

Drug Type

Interleukins

Synonyms

IL-10 (nonglycosylated), Interleukin-10

+ [2]

Target

IL-10R

Action-

Mechanism

IL-10 replacements(Interleukin-10 replacements)

Therapeutic Areas

Immune System DiseasesDigestive System Disorders

Active Indication-

Inactive Indication

Crohn DiseaseUlcerative colitis, active moderate

Originator Organization

Intrexon ActoBiotics NV

Active Organization-

Inactive Organization

Intrexon ActoBiotics NV

License Organization-

Drug Highest PhaseDiscontinuedPhase 1/2

First Approval Date-

Regulation-

Login to view timeline

Structure/Sequence

Sequence Code 33955708

IntroductionKeloids are pathological wound healing responses to dermal injuries. These scars may lead to considerable morbidity, but treatments remain challenging for physicians. Interleukin 10 (IL-10), a potent anti-inflammatory cytokine, plays a prominent role in fetal scarless regenerative healing; therefore, it may become a more targeted and effective therapy for keloids. This review aimed to obtain an overview of the background of keloid and IL-10 functions as its promising forthcoming treatment.Materials and MethodsStudies were sought from Pubmed, ScienceDirect, PLOS, and Clinical Key. Keywords are interleukin 10, keloid, and wound healing as Medical Subject Headings terms.Results and DiscussionKeloids and fetal scarless healing represent 2 opposing ends of the tissue repair spectrum. Promising multiple animal models have demonstrated successful regenerative healing promotion through IL-10 overexpression by its ability to minimize inflammatory wound microenvironment, downregulate transforming growth factor β/SMAD signaling pathway, increase extracellular matrix breakdown, and regulate extracellular matrix. These results have led to the development of clinical trials investigating human recombinant IL-10.ConclusionsInterleukin 10 has the potential to become a more targeted and promising therapy of keloids owing to its pleiotropic effects.

01 Apr 2022·Digestive Diseases and SciencesQ3 · MEDICINE

Immune Inhibitory Properties and Therapeutic Prospects of Transforming Growth Factor-Beta and Interleukin 10 in Autoimmune Hepatitis

Q3 · MEDICINE

Review

Author: Czaja, Albert J

Transforming growth factor-beta and interleukin 10 have diverse immune inhibitory properties that have restored homeostatic defense mechanisms in experimental models of autoimmune disease. The goals of this review are to describe the actions of each cytokine, review their investigational use in animal models and patients, and indicate their prospects as interventions in autoimmune hepatitis. English abstracts were identified in PubMed by multiple search terms. Full-length articles were selected for review, and secondary and tertiary bibliographies were developed. Transforming growth factor-beta expands the natural and inducible populations of regulatory T cells, limits the proliferation of natural killer cells, suppresses the activation of naïve CD8⁺ T cells, decreases the production of interferon-gamma, and stimulates fibrotic repair. Interleukin 10 selectively inhibits the CD28 co-stimulatory signal for antigen recognition and impairs antigen-specific activation of uncommitted CD4⁺ and CD8⁺ T cells. It also inhibits maturation of dendritic cells, suppresses Th17 cells, supports regulatory T cells, and limits production of diverse pro-inflammatory cytokines. Contradictory immune stimulatory effects have been associated with each cytokine and may relate to the dose and accompanying cytokine milieu. Experimental findings have not translated into successful early clinical trials. The recombinant preparation of each agent in low dosage has been safe in human studies. In conclusion, transforming growth factor-beta and interleukin 10 have powerful immune inhibitory actions of potential therapeutic value in autoimmune hepatitis. The keys to their therapeutic application will be to match their predominant non-redundant function with the pivotal pathogenic mechanism or cytokine deficiency and to avoid contradictory immune stimulatory actions.

01 May 2018·Circulation: Arrhythmia and ElectrophysiologyQ1 · MEDICINE

Interleukin 10 Treatment Ameliorates High-Fat Diet–Induced Inflammatory Atrial Remodeling and Fibrillation

Q1 · MEDICINE

Article

Author: Oniki, Takahiro ; Ayabe, Reika ; Tanino, Tomomi ; Shinohara, Tetsuji ; Aoki, Kohei ; Nakagawa, Mikiko ; Nagano, Yasuko ; Yufu, Kunio ; Fujinami, Mami ; Yoshimura, Seiichiro ; Miyoshi, Miho ; Kondo, Hidekazu ; Teshima, Yasushi ; Saito, Shotaro ; Ikebe, Yuki ; Kawano, Kyoko ; Kira, Shintaro ; Takahashi, Naohiko ; Ishii, Yumi ; Akiyoshi, Kumiko ; Masaki, Takayuki ; Okada, Norihiro ; Akioka, Hidefumi ; Abe, Ichitaro ; Mitarai, Kazuki ; Takanari, Hiroki ; Gotoh, Koro ; Fukui, Akira

Background:Obesity, characterized by systemic low-grade inflammation, is considered a well-known risk for atrial fibrillation. In fact, IL-10 (interleukin 10), which is a potent anti-inflammatory cytokine, has been reported to decrease in obese and diabetic patients. We tested the hypotheses forwarding that genetic deletion of IL-10 exacerbates high-fat diet (HFD)–induced obesity-caused atrial inflammation, lipidosis, fibrosis, and fibrillation and that IL-10 therapy inhibits this pathology.Methods:Eight- to 10-week-old male CL57/B6 (wild-type) mice and IL-10 knockout mice were divided into a 12-week HFD group and a 12-week normal-fat diet (NFD) group, respectively. In addition, the effect of IL-10 administration was also investigated.RESULTS:HFD-induced obesity for 12 weeks significantly depressed serum levels of IL-10 but were found to increase several proinflammatory cytokines in wild-type mice. Adverse atrial remodeling, including atrial inflammation, lipidosis, and fibrosis, was induced in both wild-type and IL-10 knockout mice by HFD. Vulnerability to atrial fibrillation was also significantly enhanced by HFD. With regard to epicardial and pericardial adipose tissue, the total amount of epicardial adipose tissue+pericardial adipose tissue volume was increased by HFD. Besides, proinflammatory and profibrotic cytokines of epicardial adipose tissue+pericardial adipose tissue were also upregulated. In contrast, the protein level of adiponectin was downregulated by HFD. These HFD-induced obesity-caused adverse effects were further exaggerated in IL-10 knockout mice in comparison to wild-type mice. Systemic IL-10 administration markedly ameliorated HFD-induced obesity-caused left atrial remodeling and vulnerability to atrial fibrillation, in addition to improving the quality of epicardial adipose tissue+pericardial adipose tissue.Conclusions:Our results highlight IL-10 treatment as a potential therapeutic approach to limit the progression of HFD-induced obesity-caused atrial fibrillation.

100 Deals associated with AG-011

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12880

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Ulcerative colitis, active moderate	Phase 2	Netherlands	Intrexon ActoBiotics NV	01 Jul 2008
Ulcerative colitis, active moderate	Phase 2	Sweden	Intrexon ActoBiotics NV	01 Jul 2008
Ulcerative colitis, active moderate	Phase 2	Canada	Intrexon ActoBiotics NV	01 Jul 2008
Ulcerative colitis, active moderate	Phase 2	Belgium	Intrexon ActoBiotics NV	01 Jul 2008
Crohn Disease	Phase 2	-	-	-

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ERS2018	Not Applicable	-	-	Interleukin-10	ksljharxms(blmrmrouoy) = txwukfvafe yglspirywl (fdvoyxycba ) View more	-	15 Sep 2018
ERS2018	Not Applicable	-	-	Interleukin-10	tldipzszhi(jatapajcdr) = tahqxdkrrm lkwcewlgmi (spftobevme ) View more	-	15 Sep 2018
ECCO2016	Not Applicable	-	-	Interleukin-10 (IL-10R-deficient patient)	ypvsikeeyf(cknxlseeit) = oxewsrwyvp htezsliaxc (qbwmzuecvz ) View more	-	12 Feb 2016
AAAAI2006	Not Applicable	IL-4- \| IL-13 \| IL-10	20	IL-10	gmtnrkeufk(edghrnguha) = ciomqposvc bnuimuvfko (evoxcahjcn ) View more	Positive	01 Feb 2006
AAAAI2006	Not Applicable	IL-4- \| IL-13 \| IL-10	20	No IL-10	gmtnrkeufk(edghrnguha) = dcorgrtiix bnuimuvfko (evoxcahjcn ) View more	Positive	01 Feb 2006
ARVO2003	Not Applicable	Ganglion Cysts	-	IL-10	egfnhcgech(qpswsklblp) = mmzztcghna jktxsyqjvy (ucncyiheur )	-	01 May 2003

Login to view more data

Translational Medicine

Boost your research with our translational medicine data.

login

or

view full example data

Boost your research with our translational medicine data.

Deal

Boost your decision using our deal data.

login

or

view full example data

Boost your decision using our deal data.

Core Patent

Boost your research with our Core Patent data.

login

or

view full example data

Boost your research with our Core Patent data.

Clinical Trial

Identify the latest clinical trials across global registries.

login

or

view full example data

Identify the latest clinical trials across global registries.

Approval

Accelerate your research with the latest regulatory approval information.

login

or

view full example data

Accelerate your research with the latest regulatory approval information.

Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

login

or

view full example data