Last update 01 Nov 2024

CTSS x CTSK

Last update 01 Nov 2024

Basic Info

Related Targets

CTSSCTSK

Drugs associated with CTSS x CTSK

SAR-114137

Target

CTSK x CTSS

Mechanism

CTSK inhibitors [+1]

Active Org.-

Originator Org.

Sanofi

Active Indication-

Inactive Indication

Neuralgia

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

AM-3876

Target

CTSK x CTSS

Mechanism

CTSK inhibitors [+1]

Active Org.-

Originator Org.

Amura Therapeutics Ltd.

Active Indication-

Inactive Indication

Neuralgia [+2]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Cz-007

Target

CTSK x CTSS

Mechanism

CTSK inhibitors [+1]

Active Org.-

Originator Org.

Merck & Co., Inc.

Active Indication-

Inactive Indication

Chagas Disease

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CTSS x CTSK

100 Translational Medicine associated with CTSS x CTSK

0 Patents (Medical) associated with CTSS x CTSK

Literatures (Medical) associated with CTSS x CTSK

01 Nov 2024·Journal of Hypertension

CD8+ T-cell deficiency protects mice from abdominal aortic aneurysm formation in response to calcium chloride2

Article

Author: Zhao, Mantong ; Shu, Shangzhi ; Yue, Xueling ; Cui, Rihua ; Lin, Zhuo ; Zhao, Longguo ; Zheng, Xintong ; Cheng, Xian Wu ; Piao, Jinshun ; Lei, Yanna ; Zhang, Meiping ; Zhang, Xian ; Shi, Guo-Ping

Objective:Abdominal aortic aneurysm (AAA) is an aneurysm-like dilated and highly fatal cardiovascular disease. CD8+ T cells have been shown to be critical for vascular pathological processes, but the contribution of these lymphocytes to vascular diseases remains elusive.Methods and results:Eight-week-old male wildtype (CD8+/+) and Cd8a knockout (CD8−/−) mice were used in a calcium chloride2 (CaCl2)-induced experimental AAA model. At 6 weeks after surgery, CD8+ T-cell deletion prevented the formation of AAA, accompanied by reductions of the levels of inflammatory (interferon-γ [IFN-γ], interleukin-1β, monocyte chemoattractant protein-1, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, NOD-like receptor protein 3, caspase-1), oxidative stress [NADPH oxidase and gp91phox], and proteolysis (cathepsin S, cathepsin K, matrix metalloproteinase-2 [MMP-2] and MMP-9) proteins and/or genes in plasma and/or AAA tissues. Immunoreactivities of MMP-2 and MMP-9 were observed in macrophages. An injection of IFN-γ and adoptive transfer of CD8+ T cells of IFN-γ+/+ mice diminished CD8−/−-mediated vasculoprotective actions in the AAA mice. In vitro, IFN-γ enhanced MMP-2 and MMP-9 gelatinolytic activities in macrophage and/or vascular smooth muscle cells.Conclusion:The vasculoprotective effects of CD8+ T-cell deletion in a mouse CaCl2-induced AAA model were likely attributable to, at least in part, the attenuation of IFN-γ-dependent inflammation action, oxidative stress production, and proteolysis, suggesting a novel therapeutic target for AAA formation by regulating CD8+ T-cell-derived IFN-γ secretion.

01 Nov 2024·Journal of the Science of Food and Agriculture

Combining network pharmacology and experimental verification to study the anti‐colon cancer effect and mechanism of sulforaphene

Article

Author: Yu, Zhangfu ; Shen, Ronghu ; Qu, Yang ; Li, Jianrong ; Li, Xiuxia

AbstractBACKGROUNDSulforaphene is a derivative of glucosinolate and a potential bioactive substance used for treating colon cancer. This study aimed to evaluate the potential inhibitory effect and mechanisms of sulforaphene in human colon cancer Caco‐2 cells. Network pharmacology, molecular docking, and experimental verification were performed to elucidate potential sulforaphene mechanisms in the treatment of this condition.RESULTNetwork pharmacology predicted 27 intersection target genes between sulforaphene and colon cancer cell inhibition. Key sulforaphene targets associated with colon cancer cell inhibition were identified as EGFR, MAPK14, MCL1, GSK3B, PARP1, PTPRC, NOS2, CTSS, TLR9, and CTSK. Gene ontology functional enrichment analysis revealed that the above genes were primarily related to the positive regulation of peptidase activity, cytokine production in the inflammatory response, and the cell receptor signaling pathway. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that sulforaphene mainly inhibited the proliferation of cancer cells by affecting apoptosis as well as the signaling pathways of PD‐1, Toll‐like receptor, T cell receptor, and P13k–Akt. Molecular docking results further confirmed that CTSS, GSK3B, and NOS2 were significantly up‐regulated and had good binding affinity with sulforaphene. In vitro experiments also indicated that sulforaphene had a significant inhibitory effect on human colon cancer Caco‐2 cells.CONCLUSIONThis paper revealed the pharmacodynamic mechanism of sulforaphene in the treatment of colon cancer for the first time. It provides scientific insight into the development of sulforaphene as a medicinal resource. © 2024 Society of Chemical Industry.

22 May 2023·Journal of chemical information and modeling

MD-Based Assessment of Covalent Inhibitors in Noncovalent Association Complexes: Learning from Cathepsin K as a Test Case.

Article

Author: Sotriffer, Christoph ; Endres, Erik ; Yuan Chen, Natalia

A sufficiently stable noncovalent association complex between a covalent inhibitor and its protein target is regarded as a prerequisite for the formation of a covalent complex. As this transient form can hardly be assessed experimentally, computational modeling is required to probe the suitability of a given ligand at this particular stage. To investigate which criteria should be fulfilled by suitable candidates in a molecular dynamics (MD) assessment, a systematic study was conducted with 20 complexes of cathepsin K, a papain-like cysteine protease of pharmaceutical relevance. The covalent inhibitors in these complexes were converted to their pre-reaction states, and the resulting noncovalent complexes were subjected to MD simulations. The critical distance between the electrophilic and nucleophilic reaction partners was monitored as a potential parameter to assess the suitability for covalent bond formation. Across various warhead types, a distance between 3.6 and 4.0 Å, comparable to the sum of the generalized Born radii of carbon and sulfur, was found to be stably maintained under appropriate conditions. The protonation state of the catalytic dyad and the resulting solvation pattern dramatically affected the noncovalent binding mode and the distance of the warhead to the active site. For several complexes, fluctuations in the orientation of the warhead were observed due to torsional rotations in adjacent bonds. This observation helped to explain the gradual transitions from noncovalent to covalent complexes observed in the crystal structures of three closely related nitrile-based inhibitors. According to comparative simulations conducted for a set of 13 cathepsin S complexes, the overall findings of the study appear to be transferable to related cysteine proteases as targets of covalent inhibitors.

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