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Last update 08 May 2025

ADAMTS4

Last update 08 May 2025

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

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

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

CN117136051

Patent Mining

Target

ADAMTS x ADAMTS4 x ADAMTS5 x ADAMTSL4

Mechanism

ADAMTS inhibitors

Active Org.

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Originator Org.

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Active Indication

Inflammation [+1]

Inactive Indication-

Drug Highest PhaseDiscovery

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

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

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

100 Clinical Results associated with ADAMTS4

100 Translational Medicine associated with ADAMTS4

0 Patents (Medical) associated with ADAMTS4

885

Literatures (Medical) associated with ADAMTS4

01 Apr 2025·Experimental Dermatology

RNA Sequencing Revealed Distinct Expression Profiles and Temporal Expression Dynamics in Murine Model of Foreign Body Reaction

Article

Author: Riew, Tae‐Ryong ; Kim, Tae Keun ; Kim, Yoon‐Seob ; Hwang, Ji‐Won

ABSTRACTForeign body reaction (FBR) is an inflammatory and fibrotic reaction to degradation‐resistant foreign materials characterised by the temporal cascade of cellular and molecular dynamics, which remains not fully elucidated. The aim of our study was to elucidate the temporal gene expression profiles of FBR. An FBR model was generated by implanting polycaprolactone into the abdominal subcutaneous layer of C57BL/6 mice. RNA sequencing was performed using established FBR tissues at various time points after implantation (FBR group; 2, 4, 8 and 12 weeks, n = 4 for each time points), and normal dorsal skin of mice as the control group (n = 3). We identified distinct gene expression profiles between the control group and the FBR group. Extracellular matrix (ECM), immune, and epigenetics‐related genes were significantly enriched in the FBR group compared to normal skin. Within the FBR groups, expression profiles did not show definitive segregation across time points. We observed the highest expression of ECM‐related genes (Adamts4, Col9a3, Col6a2, and Furin) and pathways in the 2‐week samples, followed by a gradual down‐regulation thereafter. In conclusion, our study elucidated distinct expression profiles of FBR in comparison to normal skin, as well as the temporal expression dynamics of FBR.

01 Mar 2025·JOR SPINE

Ruxolitinib Delays Nucleus Pulposus Cell Senescence in Rat Intervertebral Discs

Article

Author: Yakefu, Abulizi ; Hao, Honggang ; Xun, Chuanhui ; Zhang, Shuwen ; Cai, Xiaoyu ; Liang, Weidong ; Xu, Tao ; Sheng, Weibin ; Gao, Shutao ; Cao, Rui

ABSTRACTBackgroundIntervertebral disc degeneration involves aging and senescence of nucleus pulposus cells (NPCs), and JAK/STAT signaling may contribute to this process. The aim of this study was to investigate the therapeutic effect of the JAK2 inhibitor, ruxolitinib, on NPC senescence.MethodsControl (third passage), Senescence (sixth passage), JAK inhibitor (ruxolitinib‐treated), siRNA‐NC (control siRNA‐treated), and siRNA‐JAK2 (JAK2‐targeting siRNA‐treated) groups of rat NPCs were established. Cell senescence ratios were determined by β‐galactosidase staining and Edu staining was conducted to assess cell proliferation. Cell cycle and apoptosis were analyzed by flow cytometry and Aggrecan and Col II expression detected by immunofluorescence staining. Levels of IL‐1β, IL‐6, TNF‐α, MMP‐3, and MMP‐13 were detected by ELISA, and p16, p21, p53, p‐p53, JAK2, STAT3, p‐JAK2, p‐STAT3, ADAMTS4, and ADAMTS5 levels were examined by western blot.ResultsMore cell senescence was detected by β‐galactosidase staining in the Senescence group than in the Control group, while cell proliferation was lower, apoptosis ratio higher, and the percentage of NPCs in G0/G1 phase higher. Levels of senescence‐related proteins, including p16, p21, p53, and p‐p53, were higher in the Senescence group than the Control group, as were those of IL‐1β, IL‐6, TNF‐α, MMP‐3, MMP‐13, ADAMTS4, and ADAMTS5. Further, Aggrecan and Col II levels were lower in the Senescence group, while those of JAK2 and STAT3 (JAK2/STAT3 signaling pathway) were higher. Ruxolitinib reversed the changes described above to varying degrees, and the results were supported by those of experiments involving targeted silencing of JAK2.ConclusionsNPC senescence is characterized by low cell proliferation, a high apoptosis ratio, cell cycle arrest, and generation of senescence‐associated secretory phenotypes. NPC senescence can be delayed by inhibiting JAK2/STAT3 signaling using ruxolitinib.

01 Mar 2025·Gene Therapy

PCRX-201, a novel IL-1Ra gene therapy treatment approach for low back pain resulting from intervertebral disc degeneration

Article

Author: Le Maitre, Christine L. ; Whitt, Joshua P ; Jackson, J Derek ; Whitt, Joshua P. ; Senter, Rebecca K ; Snuggs, Joseph W ; Senter, Rebecca K. ; Snuggs, Joseph W. ; Le Maitre, Christine L ; Jackson, J. Derek

AbstractLow back pain is the leading cause of global disability with intervertebral disc (IVD) degeneration a major cause. However, no current treatments target the underlying pathophysiological causes. PCRX-201 presents a novel gene therapy approach that addresses this issue. PCRX-201 codes for interleukin-1 receptor antagonist, the signalling inhibitor of the pro-inflammatory cytokine interleukin-1, which orchestrates the catabolic degeneration of the IVD. Here, the ability of PCRX-201 to transduce human nucleus pulposus cells to increase IL-1Ra production was assessed together with effects on catabolic pathways. When transduced with PCRX-201, the production and release of IL-1Ra was increased in degenerate human nucleus pulposus cells and tissue. Whereas, the production of downstream proteins, including IL-1β, IL-6, MMP3, ADAMTS4 and VEGF were decreased in both cells and tissue, indicating a reduction in IL-1-induced catabolic signalling. Here, a novel gene therapy vector, PCRX-201, was shown to transduce degenerate NP cells and tissue, increasing the production of IL-1Ra. The increased IL-1Ra resulted in decreased production of catabolic cytokines, enzymes and angiogenic factors, whilst also increasing aggrecan expression. This demonstrates PCRX-201 enables the inhibition of IL-1-driven IVD degeneration. The ability of PCRX-201 to elicit anti-catabolic responses is promising and warrants further development to determine the efficacy of this exciting, novel gene therapy.

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ADAMTS4

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