Last update 01 Nov 2024

NFATC1 x Cytokines

Last update 01 Nov 2024

Basic Info

Related Targets

NFATC1Cytokines

Drugs associated with NFATC1 x Cytokines

UR-1505

Target

Cytokines x NFATC1

Mechanism

Cytokines inhibitors [+2]

Active Org.-

Originator Org.

Palau Pharma SA

Active Indication-

Inactive Indication

Dermatitis, Atopic [+4]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with NFATC1 x Cytokines

EUCTR2007-005672-13-FR / Unknown statusNot Applicable

DOUBLE-BLIND STUDY, RANDOMISED, ACTIVE AND PLACEBO CONTROLLED TO ASSESS THE CLINICAL EFFICACY, SKIN TOLERABILITY AND PHARMACOLOGICAL ACTIVITY OF UR-1505 OINTMENT AT THREE DIFFERENT STRENGHTS IN PATIENTS WITH MILD TO MODERATE PLAQUE-TYPE PSORIASIS

Start Date28 Dec 2007

Sponsor / Collaborator

Palau Pharma SA

EUCTR2007-002550-27-FR / Unknown statusNot Applicable

DOUBLE-BLIND, RANDOMISED, ACTIVE AND PLACEBO CONTROLLED STUDY TO ASSESS THE CLINICAL EFFICACY, SKIN TOLERABILITY AND PHARMACOLOGICAL ACTIVITY OF A NEW TOPICAL COMPOUND (UR-1505 0.5%, 1% AND 2%) IN PATIENTS WITH MILD TO MODERATE ATOPIC DERMATITIS

Start Date31 Jul 2007

Sponsor / Collaborator

Palau Pharma SA

100 Clinical Results associated with NFATC1 x Cytokines

100 Translational Medicine associated with NFATC1 x Cytokines

0 Patents (Medical) associated with NFATC1 x Cytokines

1,226

Literatures (Medical) associated with NFATC1 x Cytokines

01 Dec 2024·International Immunopharmacology

Targeting EZH2 attenuates the ferroptosis-mediated osteoblast–osteoclast imbalance in rheumatoid arthritis

Article

Author: Li, Yongming ; Piao, Xuemei ; He, Feng ; Xue, Luan ; Li, Na ; Yan, Yixin ; Wu, Xiangxiang

OBJECTIVEThe enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) can regulate osteogenesis and osteoclastogenesis. This study aimed to further explore the effects of EZH2 modification on ferroptosis and the osteoblast-osteoclast balance in rheumatoid arthritis (RA) in vitro and in vivo.METHODSBone marrow mesenchymal stromal cells were transfected with EZH2 overexpression (oeEZH2) and EZH2 shRNA (shEZH2) plasmids with or without ferrostatin-1 (Fer-1) treatment and subjected to an osteoblast differentiation assay. The cells were then cocultured with bone marrow-derived macrophages and subjected to an osteoclast differentiation assay. Collagen-induced arthritis (CIA) mice were generated and injected with shEZH2 adeno-associated virus (AAV).RESULTSOeEZH2 repressed osteoblast differentiation, as reflected by decreased ALP and Alizarin Red S staining and increased OPN, RUNX2, OPG and RANKL; however, shEZH2 had the opposite effects. Besides, oeEZH2 promoted osteoblast ferroptosis, as suggested by increased MDA, Fe²⁺, ROS, and PTGS2 but decreased GPX4 and SLC7A11; these effects could be attenuated by Fer-1 treatment. In contrast, shEZH2 ameliorated osteoblast ferroptosis. OeEZH2 subsequently increased osteoclast differentiation, as indicated by increased TRAP⁺ multinucleated cells, NFATC1, CTSK, and c-FOS; however, shEZH2 had the opposite effect, except that it did not regulate CTSK. In CIA mice, shEZH2 AAV decreased the clinical symptom score, histological score of cartilage, and systemic inflammation (TNF-α and IL-6) and repressed bone ferroptosis and restored the osteoblast-osteoclast balance to some extent, as reflected by immunohistochemical staining of related markers.CONCLUSIONTargeting EZH2 attenuates the ferroptosis-mediated osteoblast-osteoclast imbalance in RA, revealing its potential as a treatment target.

01 Dec 2024·Molecular Biology Reports

Selenoprotein W engages in overactive osteoclast differentiation in multiple myeloma

Article

Author: Lee, Kyung Hee ; Oh, Jiin ; Kim, Min Kyoung ; Jeong, Daewon ; Kim, Hyunsoo

AbstractBackgroundPatients with multiple myeloma exhibit malignant osteolytic bone disease due to excessive osteoclast formation and function. We recently identified that osteoclastogenic stimulator selenoprotein W (SELENOW) is upregulated via ERK signaling and downregulated via p38 signaling during receptor activator of nuclear factor (NF)-κΒ ligand (RANKL)-induced osteoclast differentiation. In the intrinsic physiological process, RANKL-induced downregulation of SELENOW maintains proper osteoclast differentiation; in contrast, forced overexpression of SELENOW leads to overactive osteoclast formation and function.Methods and resultsWe observed that SELENOW is highly expressed in multiple myeloma-derived peripheral blood mononuclear cells (PBMCs) and mature osteoclasts when compared to healthy controls. Also, the level of tumor necrosis factor alpha (TNFα), a pathological osteoclastogenic factor, is increased in the PBMCs and serum of patients with multiple myeloma. ERK activation by TNFα was more marked and sustained than that by RANKL, allowing SELENOW upregulation. Excessive expression of SELENOW in osteoclast progenitors and mature osteoclasts derived from multiple myeloma facilitated efficient nuclear translocation of osteoclastogenic transcription factors NF-κB and NFATc1, which are favorable for osteoclast formation.ConclusionOur findings suggest a possibility that feedforward signaling of osteoclastogenic SELENOW by TNFα derived from multiple myeloma induces overactive osteoclast differentiation, leading to bone loss during multiple myeloma.

01 Dec 2024·International Immunopharmacology

Corydaline attenuates osteolysis in rheumatoid arthritis via mitigating reactive oxygen species production and suppressing calcineurin-Nfatc1 signaling

Article

Author: Feng, Changgong ; Zhang, Xin ; Li, Ziqing ; Sun, Shui ; Wang, Haojue ; Lu, Qizhen ; Wang, Yi ; Yuan, Tao

AIM OF THE STUDYOsteolysis in Rheumatoid arthritis (RA) is principally provoked by osteoclast hyperactivity. This study aims to employ Corydaline (Cory), a plant extract, as an osteoclast inhibitor in treating RA-inflicted osteolysis while unveiling the corresponding mechanism.MATERIALS AND METHODSOsteoclasts were derived from mouse bone marrow-derived monocytes (BMMs) stimulated with M-CSF and RANKL. Subsequently, utilizing network pharmacology, we performed a thorough analysis of Cory's molecular structure and discerned its preliminary therapeutic potential. Subsequently, LPS was used to simulate and establish an in vitro model of RA, and the biological effect of Cory on osteoclast behaviors was evaluated through various staining methods, RT-qPCR, and Western blot. In addition, a collagen-induced arthritis (CIA) mouse model was developed to evaluate the therapeutic effects of Cory in vivo.RESULTSThe results from network pharmacology indicated a significant correlation between Cory, oxidative stress, and calcium signaling. Subsequent in vitro experiments demonstrated Cory's capacity to inhibit the formation and function of osteoclast under inflammatory stimuli, thereby protecting against abnormal bone resorption. This effect is achieved by activating the Nrf2 signaling pathway, mitigating the generation of reactive oxygen species (ROS), and modulating the calcineurin-Nfatc1 signaling. Furthermore, this therapeutic effect of Cory on RA-associated osteolysis was proved in CIA mice models.CONCLUSIONSCory demonstrates the potential to activate the Nrf2 signaling pathway, effectively countering oxidative stress, and simultaneously inhibit the calcineurin-Nfatc1 signaling pathway to regulate the terminals of calcium signaling. These dual effects collectively reduce osteoclast activity, ultimately contributing to a therapeutic role in RA osteolysis. Therefore, our study presents Cory as a novel pharmaceutical candidate for the prevention and treatment of RA.

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