Last update 01 Nov 2024

ADAMTS4

Last update 01 Nov 2024

Basic Info

Synonyms

A disintegrin and metalloproteinase with thrombospondin motifs 4, a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 4, ADAM metallopeptidase with thrombospondin type 1 motif 4

+ [8]

Introduction

Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover. May play an important role in the destruction of aggrecan in arthritic diseases. Could also be a critical factor in the exacerbation of neurodegeneration in Alzheimer disease. Cleaves aggrecan at the '392-Glu-|-Ala-393' site.

Drugs associated with ADAMTS4

ADAMTS5/ADAMTS4 Inhibitor (JiangSu Hengrui)

Target

ADAMTS4 x ADAMTS5

Mechanism

ADAMTS4 inhibitors [+1]

Active Org.

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Originator Org.

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Active Indication

Osteoarthritis [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

GFC-301

Target

ADAMTS4

Mechanism

ADAMTS4 gene inhibitors

Active Org.

GeneFrontier Corp.

Originator Org.

GeneFrontier Corp.

Active Indication

Osteoarthritis [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Small Molecules Inhibitor of ADAMTS4 and ADAMTS5(Eli Lilly and Co)

Target

ADAMTS4 x ADAMTS5

Mechanism

ADAMTS4 inhibitors [+1]

Active Org.

Eli Lilly & Co.

Originator Org.

Eli Lilly & Co.

Active Indication

Osteoarthritis

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with ADAMTS4

NCT00454298 / CompletedPhase 1

A Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Regimen, Parallel-Group Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AGG-523 Administered Orally to Subjects With Severe Osteoarthritis

The main purpose of the study is to find out if, after 4 weeks of dosing, signs of the investigational drug AGG-523, or its effects, can be measured in urine, blood, or the knee joint. A secondary purpose is to evaluate the safety of taking the drug either once a day or twice a day for 4 weeks.

Start Date01 May 2007

Sponsor / Collaborator

Wyeth AB

NCT00434785 / CompletedPhase 1

An Ascending, Multiple Dose Study of the Safety, Tolerability, and Pharmacokinetics of AGG-523 Administered Orally to Healthy Male Japanese Subjects.

To assess the safety and tolerability of ascending, multiple oral doses of AGG-523 in healthy Japanese subjects.

Start Date01 Feb 2007

Sponsor / Collaborator

Wyeth AB

NCT00427687 / CompletedPhase 1

A Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose, Parallel-Group Study of the Pharmacodynamics, Safety, Tolerability, and Pharmacokinetics of AGG-523 Administered Orally to Subjects With Mild to Moderate Osteoarthritis

This study will evaluate the effect of AGG-523 administration on biomarkers related to osteoarthritis. Safety and tolerability of AGG-523 will also be assessed.

Start Date01 Feb 2007

Sponsor / Collaborator

Wyeth AB

100 Clinical Results associated with ADAMTS4

100 Translational Medicine associated with ADAMTS4

0 Patents (Medical) associated with ADAMTS4

919

Literatures (Medical) associated with ADAMTS4

31 Dec 2024·Redox Report

Evaluating anticancer activity of emodin by enhancing antioxidant activities and affecting PKC/ADAMTS4 pathway in thioacetamide-induced hepatocellular carcinoma in rats

Article

Author: Bahattab, Omar ; Al-Gayyar, Mohammed M H ; Hamdan, Ahmed M ; Hassan, Hanan M ; Alattar, Abdullah ; Alshaman, Reem

Emodin is a naturally occurring anthraquinone derivative with a wide range of pharmacological activities, including neuroprotective and anti-inflammatory activities. We aim to assess the anticancer activity of emodin against hepatocellular carcinoma (HCC) in rat models using the proliferation, invasion, and angiogenesis biomarkers. After induction of HCC, assessment of the liver impairment and the histopathology of liver sections were investigated. Hepatic expression of both mRNA and protein of the oxidative stress biomarkers, HO-1, Nrf2; the mitogenic activation biomarkers, ERK5, PKCδ; the tissue destruction biomarker, ADAMTS4; the tissue homeostasis biomarker, aggregan; the cellular fibrinolytic biomarker, MMP3; and of the cellular angiogenesis biomarker, VEGF were measured. Emodin increased the survival percentage and reduced the number of hepatic nodules compared to the HCC group. Besides, emodin reduced the elevated expression of both mRNA and proteins of all PKC, ERK5, ADAMTS4, MMP3, and VEGF compared with the HCC group. On the other hand, emodin increased the expression of mRNA and proteins of Nrf2, HO-1, and aggrecan compared with the HCC group. Therefore, emodin is a promising anticancer agent against HCC preventing the cancer prognosis and infiltration. It works through many mechanisms of action, such as blocking oxidative stress, proliferation, invasion, and angiogenesis.

01 Dec 2024·Molecular Biology Reports

Early insights into the role of Exoc6B associated with spondyloepimetaphyseal dysplasia with joint laxity type 3 in primary ciliogenesis and chondrogenic differentiation in vitro

Article

Author: Quadri, Neha ; Upadhyai, Priyanka ; Guleria, Vishal Singh ; Das, Ranajit ; Prasad, Keshava

BACKGROUNDSpondyloepimetaphyseal dysplasia with joint laxity type 3 (SEMDJL3) is a rare skeletal dysplasia associated with EXOC6B, a component of the exocyst complex, involved in vesicle tethering and exocytosis at the plasma membrane. So far, EXOC6B and the pathomechanisms underlying SEMDJL3 remain obscure.METHODS AND RESULTSExoc6b was detected largely at the perinuclear regions and the primary cilia base in ATDC5 prechondrocytes. Its shRNA lentiviral knockdown impeded primary ciliogenesis. In Exoc6b silenced prechondrocytes, Hedgehog signaling was attenuated, including when stimulated with Smoothened agonist. Exoc6b knockdown deregulated the mRNA and protein levels of Col2a1, a marker of chondrocyte proliferation at 7- and 14-days following differentiation. It led to the upregulation of Ihh another marker of proliferative chondrocytes. The levels of Col10a1, a marker of chondrocyte hypertrophy was enhanced at 14 days of differentiation. Congruently, Axin2, a canonical Wnt pathway modulator that inhibits chondrocyte hypertrophy was repressed. The expression of Mmp13 and Adamts4 that are terminal chondrocyte hypertrophy markers involved in extracellular matrix (ECM) remodelling were downregulated at 7 and 14 days of chondrogenesis. Bglap that encodes for the most abundant non-collagenous bone matrix constituent and promotes ECM calcification was suppressed at 14 days of chondrocyte differentiation. ECM mineralization was assessed by Alizarin Red staining. Gene expression and ciliogenesis were investigated by reverse transcription quantitative real-time PCR, immunoblotting, and immunocytochemistry.CONCLUSIONSThese findings provide initial insights into the potential role of Exoc6b in primary ciliogenesis and chondrogenic differentiation, contributing towards a preliminary understanding of the molecular pathomechanisms underlying SEMDJL3.

01 Dec 2024·Molecular Biology Reports

Chrysin downregulates the expression of ADAMTS-4 in foam cells

Article

Author: Mohan, Mithra S ; Boban, P T ; Saja, K ; Jayan, Sreelekshmi G ; Aswani, S S ; Aparna, N S

BACKGROUNDChrysin, a polyphenolic compound, possesses antioxidant and anti-inflammatory properties. In this study, we investigated the effect of chrysin on the expression of A disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), a protease enzyme involved in degrading extracellular matrix associated with atherosclerosis.METHODS AND RESULTSWe have studied the cell viability by MTT assay and foam cell formation by oil red O staining. The mRNA and protein expression of ADAMTS-4 was studied using quantitative polymerase chain reaction (qPCR) and Western blotting, respectively. Our study showed that chrysin significantly downregulates the expression of ADAMTS-4 in foam cells.CONCLUSIONChrysin's ability to downregulate the expression of ADAMTS-4, a protease involved in degrading the extracellular matrix, bestows upon it a new therapeutic potential for managing atherosclerosis.

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ADAMTS4

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