Last update 01 Nov 2024

PKN3

Last update 01 Nov 2024

Basic Info

Synonyms

PKN3, PKNBETA, protein kinase N3

+ [4]

Introduction

Contributes to invasiveness in malignant prostate cancer.

Drugs associated with PKN3

compound 5a (Sichuan University)

Target

PKN3

Mechanism

PKN3 inhibitors

Active Org.

Sichuan University

Originator Org.

Sichuan University

Active Indication

Tuberculosis

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Atu-027

Target

PKN3

Mechanism

PKN3 inhibitors [+1]

Active Org.-

Originator Org.

Silence Therapeutics Plc

Active Indication-

Inactive Indication

Advanced Malignant Solid Neoplasm [+4]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with PKN3

NCT01808638 / CompletedPhase 1/2

A PHASE Ib/IIa STUDY OF COMBINATION THERAPY WITH GEMCITABINE AND ATU027 IN SUBJECTS WITH LOCALLY ADVANCED OR METASTATIC PANCREATIC ADENOCARCINOMA

The purpose of the study is to evaluate a new treatment strategy for advanced pancreatic cancer disease by combining the new investigational medicinal product Atu027 with the standard chemotherapeutic gemcitabine. This combination aims at enhancing gemcitabine´s anti-tumor activity with Atu027.
The objectives of this clinical trial are to evaluate safety and activity of two Atu027 schedules in combination with standard gemcitabine treatment in patients with advanced or metastatic pancreatic adenocarcinoma.

Start Date01 Mar 2013

Sponsor / Collaborator

Silence Therapeutics GmbH

[+2]

NCT00938574 / CompletedPhase 1

A Prospective, Open-label, Single Center, Dose Finding Phase I-study With Atu027 (an siRNA Formulation) in Subjects With Advanced Solid Cancer

This is a phase I, prospective, open-label, single center, dose finding study with Atu027 (an siRNA formulation) given as single treatment followed by repeated treatment (repeated treatment phase: 8 treatments within 4 weeks) as therapy in subjects with advanced solid cancer.

Start Date01 Jun 2009

Sponsor / Collaborator

Silence Therapeutics GmbH

100 Clinical Results associated with PKN3

100 Translational Medicine associated with PKN3

0 Patents (Medical) associated with PKN3

676

Literatures (Medical) associated with PKN3

07 Oct 2024·Cell journal

Poncirin Impact on Human HER2 Breast Cancer Cells: Inhibiting Proliferation, Metastasis, and Tumor Growth in Mice Potentially through The PI3K/AKT Pathway.

Article

Author: Liu, Yuanwei ; Yun, Hao ; Zhang, Jin ; Zhou, Jinwen ; Jing, Li

OBJECTIVEBreast cancer is a prevalent and heterogeneous disease, with human epidermal growth factor receptor-2 (HER2) overexpression occurring in over 20% of cases. Poncirin, a biologically active flavonone derived from the immature dried fruits of Poncirus trifoliata, is a 7-O-neohesperidoside of isosakuranetin with a well-documented history in traditional Chinese medicine for its health-promoting properties. While the previous research hinted at its potential as an anticancer agent, its specific effects on HER2 overexpressing breast cancer cells remain largely unexplored. The aim of this study is to investigate the specific effects of Poncirin, on HER2 overexpressing breast cancer cells.MATERIALS AND METHODSIn experimental study, we assessed cell proliferation using the CCK-8 assay and explored cell migration and invasion with transwell assays. Additionally, we evaluated colony formation ability and examined apoptosis through the acridine orange/ethidium bromide (AO/EB) and Annexin V-fluorescein isothiocyanate (FITC)/ propidium iodide (PI) staining methods. The study also delved into the molecular mechanisms involved by scrutinizing the phosphatidylinositol 3-kinase/serine-threonine protein kinase (PI3K/AKT) signaling pathway via Western blotting. Furthermore, the researchers conducted in vivo experiments using mouse models to corroborate the findings in a living organism.RESULTSPoncirin demonstrated a remarkable ability to selectively inhibit proliferation and metastasis of HER2 overexpressing breast cancer cells. Mechanistically, the compound seemed to exert its effects by modulating the PI3K/AKT signaling pathway, implying its central role in the observed anticancer effects. These findings were further substantiated by in vivo experiments, which consistently showed a reduction in tumor growth when poncirin was administered.CONCLUSIONThis study underscores potential of poncirin as a potent agent for restraining the growth and metastasis of HER2 overexpressing breast cancer cells. The evidence suggests that poncirin efficacy may be attributed to its modulation possibly through PI3K/AKT pathway.

01 Oct 2024·Molecular Neurobiology

Cyclin-dependent Kinase 5 and Neurodegenerative Diseases

Review

Author: Zhao, Xiulan ; Qiang, Yalong ; Song, Fuyong ; Song, Mingxue

Neurodegenerative diseases are a group of diseases characterized by the progressive loss of neurons, including Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis. These diseases have a high incidence and mortality rate globally, placing a heavy burden on patients and their families. The pathogenesis of neurodegenerative diseases is complex, and there are no effective treatments at present. Cyclin-dependent kinase 5 is a proline-directed serine/threonine protein kinase that is closely related to the development and function of the nervous system. Under physiological conditions, it is involved in regulating the process of neuronal proliferation, differentiation, migration, and synaptic plasticity. Moreover, there is increasing evidence that cyclin-dependent kinase 5 also plays an important role in the pathogenesis of neurodegenerative diseases. In this review, we address the biological characteristics of cyclin-dependent kinase 5 and its role in neurodegenerative diseases. In particular, this review highlights the underlying mechanistic linkages between cyclin-dependent kinase 5 and mitochondrial dysfunction, oxidative stress and neuroinflammation in the context of neurodegeneration. Finally, we also summarize the currently available cyclin-dependent kinase 5 inhibitors and their prospects for the treatment of neurodegenerative diseases. Taken together, a better understanding of the molecular mechanisms of cyclin-dependent kinase 5 involved in neurodegenerative diseases can lead to the development of new strategies for the prevention and treatment of these devastating diseases.

01 Aug 2024·Molecular Diversity

An updated literature on BRAF inhibitors (2018–2023)

Review

Author: Maji, Lalmohan ; Teli, Ghanshyam ; Ghara, Abhishek ; Sengupta, Sindhuja ; Raghavendra, Nulgumnalli Manjunathaiah ; Matada, Gurubasavaraja Swamy Purawarga ; Pal, Rohit

BRAF is the most common serine-threonine protein kinase and regulates signal transduction from RAS to MEK inside the cell. The BRAF is a highly active isoform of RAF kinase. BRAF has two domains such as regulatory and kinase domains. The BRAF inhibitors bind in the c-terminus of the kinase domain and inhibit the downstream pathways. The mutation occurs mainly in the A-loop of the kinase domain. The mutation occurs due to a conversion of valine to glutamate/lysine/arginine/aspartic acid at 600th position. Among the diverse mutations, BRAF^V600E is the most common and responsible for numerous cancer such as melanoma, colorectal, ovarian, and thyroid cancer. Due to mutations in RAC1, loss of PTEN, NF1, CCND1, USP28-FBW7 complex, COT overexpression, and CCND1 amplification, the BRAF kinase enzyme developed resistance over the commercially available BRAF inhibitors. There is still unmute urgence for the development of BRAF inhibitors to overcome the persistent limitation such as resistance, mutation, and adverse effects of drugs. In the current study, we described the structure, activation, downstream signaling pathway, and mutation of BRAF. Our group also provided a detailed review of BRAF inhibitors from the last five years (2018-2023) highlighting the structure-activity relationship, mechanistic study, and molecular docking studies. We hope that the current analysis will be a useful resource for researchers and provide chemists a glimpse into the future as design and development of more effective and secure BRAF kinase inhibitors.

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PKN3

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