Serine protease x CD14

Last update 08 May 2025

Basic Info

Related Targets

Serine proteaseCD14

Drugs associated with Serine protease x CD14

MR-1007

Target

CD14 x Serine protease

Mechanism

CD14 inhibitors [+1]

Active Org.-

Originator Org.

Mochida Pharmaceutical Co., Ltd.

Active Indication-

Inactive Indication

Infectious Diseases

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with Serine protease x CD14

100 Translational Medicine associated with Serine protease x CD14

0 Patents (Medical) associated with Serine protease x CD14

377

Literatures (Medical) associated with Serine protease x CD14

01 Apr 2025·Cancer Medicine

A Phase I/IB, Open Label, Dose Finding Study to Evaluate Safety, Pharmacodynamics and Efficacy of Pembrolizumab in Combination With Vorinostat in Patients With Advanced Prostate, Renal or Urothelial Carcinoma

Article

Author: Colligan, Sean ; Quinn, David I. ; Pili, Roberto ; Adra, Nabil ; Burney, Heather N. ; Hahn, Noah M. ; Logan, Theodore

ABSTRACTBackgroundImmunosuppressive factors such as regulatory T cells and myeloid‐derived suppressive cells (MDSCs) limit the efficacy of immunotherapies. Histone deacetylase (HDAC) inhibitors have been shown to have immunomodulatory effects. Thus, we conducted a Phase Ib clinical study with the HDAC inhibitor vorinostat and the PD‐1 inhibitor pembrolizumab in patients (pts) with metastatic urothelial (UC), renal (RCC) and prostate (PCA) carcinoma.MethodsThe phase I portion consisted of two dose levels of vorinostat (100 and 200 mg, PO daily 2 weeks ON and 1 week OFF) and a fixed dose of pembrolizumab (200 mg IV every 21 days). Patients (pts) were assigned to three cohorts: Cohort A (previously treated, anti‐PD1/PD‐L1 naïve UC and RCC), Cohort B (previously treated, anti‐PD1/PD‐L1 resistant UC and RCC pts), and Cohort C (PCA pts).ResultsDose levels 1 and 2 were completed without DLTs. We have enrolled 44 pts. (36 evaluable) in the dose expansion cohorts, and the most common resolved grade 3/4 toxicities were diarrhea, hypophosphatemia, acute kidney injury, anemia, and hypothyroidism. For Cohort A (13 pts), B (11 pts), and C (12 pts) the objective response rate was 8%, 0%, and 17%, and the median progression‐free survival was 2.9, 3.5, and 3.5 months, respectively. Four partial responses were observed, and two PCA pts. had a complete biochemical response with undetectable PSA. Persistent lower levels of peripheral CD11+, CD14+ HLA‐DR− monocytic MDSCs were associated with clinical benefit.ConclusionThe combination of vorinostat and pembrolizumab is relatively well tolerated and may be active in a subset of immune checkpoint‐resistant UC/RCC pts. and immune checkpoint‐naïve PCA pts.Trial Registration: NCT02619253

01 Apr 2025·Rheumatology

A novel inhibitory pathway of synovial inflammation exerted by glucocorticoids and tumour necrosis factor inhibitors via lymphocyte activation gene-3 up-regulation: an ex vivo study

Article

Author: Gertel, Smadar ; Elkayam, Ori ; Polachek, Ari ; Furer, Victoria ; Eviatar, Tali

AbstractObjectiveTo investigate the impact of glucocorticoids (GCs) and anti-rheumatic drugs on lymphocyte activation gene-3 (LAG-3) and on programmed cell death-1 (PD-1) expression by synovial and peripheral cells ex vivo.MethodsSynovial fluid mononuclear cells (SFMCs) from psoriatic arthritis (PsA, n = 26) and rheumatoid arthritis (RA, n = 13) patients, synovial fluid cells (SFCs) from osteoarthritis (OA, n = 5) patients and peripheral blood mononuclear cells (PBMCs) of healthy donors (n = 14) were co-cultured with GCs, glucocorticoid receptor antagonist RU486, methotrexate (MTX) and biologics. LAG-3 and PD-1 expression on immune subsets were analysed by flow cytometry.ResultsGCs in PsA inhibited SFMC growth vs medium [2.3 (0.4) × 105vs 5.3 (0.7) × 105, respectively, P < 0.01] and markedly up-regulated CD14+LAG-3+ cells [11.7 (2.4)% vs 0.8 (0.3)%, P < 0.0001, respectively], but not CD3+LAG-3+ and CD14+PD-1+ cells. MTX had no effect on CD14+LAG-3+ cells [0.7 (0.3)%]. The TNF inhibitors infliximab (IFX) and etanercept, but not IL-12/23 inhibitor, up-regulated CD14+LAG-3+ cells vs medium [2.0 (0.6)% and 1.6 (0.4)% vs 0.5 (0.1)%, P < 0.03, respectively]. SFMC growth inhibition by GC in both PsA and RA correlated with CD14+LAG-3+ cell up-regulation (r = 0.53, P = 0.03). RU486 inhibited GC-induced CD14+LAG-3+ cells up-regulation in a dose-dependent manner compared with GC alone [5 µM 5.3 (1.2)% and 50 µM 1.3 (0.5)% vs 7.0 (1.4)%, P < 0.003], but had no significant effect on CD14+LAG-3+ cells co-cultured with IFX. GCs in healthy donors’ PBMCs up-regulated the immune subsets CD3+LAG-3+, CD14+LAG-3+ and CD14+PD-1+ cells.ConclusionThis study proposes a novel regulatory mechanism of GCs and of TNF inhibitors mediated by LAG-3 up-regulation in synovial cells and PBMCs. LAG-3 modulation may be a promising target for development of novel therapies for inflammatory arthritis.

10 Feb 2025·International Journal of Medical Sciences

Exploring the Plasma Proteome: Identifying Hub Proteins linking Aging, Homeostasis, and Organ Function

Article

Author: Wang, Zhaoping ; Yuan, Huiping ; Yang, Ze ; Gao, Danni ; Liu, Dizhi ; Gao, Fei ; Jiang, Mingjun ; Zhou, Yan ; Jiao, Juan ; Fang, Sihang ; Zhao, Hongye

As effectors of interactions between genes and the environment, plasma proteins can monitor homeostasis and reflect the aging state of an organism. However, biomarkers of aging that are associated with homeostasis are still unclear. This study investigates the phenotype-related plasma proteome profiles of healthy individuals and to identify proteins that are specifically related to aging and physiological indices and their expression patterns across the lifespan. From September 2020 to March 2021, 71 participants aged over 20 to 100 years were enrolled in this cross-sectional study. Data were analyzed from April 2021 to December 2023. The plasma proteome was analyzed to identify proteins that are specifically related to aging and their expression patterns across the lifespan. Then, hub proteins were screened through correlation of aging proteins with physiological and biochemical phenotypes. Based on levels of plasma proteins, physiological indices are associated with age. Additionally, these differences in protein expression correlate with age and physiological indices. Finally, we identified 20 hub proteins that correlate with both physiological indices and age, and these proteins are involved in oxidative stress, inflammation and metabolism. Bibliometric analysis confirmed that 8 hub proteins (CD44, CD14, IGF2, CFD, LBP, IGFBP3, EFEMP1, and AHSG) associated with age affect organ function by mediating homeostasis. Plasma proteins associated with both age and physiological indices are involved in oxidative stress, inflammation, and metabolism. This is the first investigation to link aging and homeostasis based on plasma proteins.

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