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Last update 08 May 2025

PLEK

Last update 08 May 2025

Basic Info

Synonyms

P47, Platelet 47 kDa protein, pleckstrin

+ [1]

Introduction

Major protein kinase C substrate of platelets.

Drugs associated with PLEK

PLEK inhibitor (PHusis Therapeutics)

Target

PLEK

Mechanism

PLEK inhibitors

Active Org.

Phusis Therapeutics, Inc.

Originator Org.

Phusis Therapeutics, Inc.

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PLEK

100 Translational Medicine associated with PLEK

0 Patents (Medical) associated with PLEK

577

Literatures (Medical) associated with PLEK

01 Apr 2025·Biogerontology

Immune genes involved in synaptic plasticity during early postnatal brain development contribute to post-stroke damage in the aging male rat brain

Article

Author: Hermann, Dirk M ; Pirscoveanu, Denisa F V ; Olaru, Denissa Greta ; Ghinea, Flavia Semida ; Doeppner, Thorsten R ; Popa-Wagner, Aurel

Stroke remains a leading cause of mortality and long-term disability worldwide, underscoring the urgent need to identify novel therapeutic targets to enhance brain circuitry repair and functional recovery. This study explores the concept of longevity assurance genes, which primarily function within genetic pathways responsible for repair and maintenance. These pathways encompass molecular and metabolic processes as well as organ- and system-level functions. To investigate this, we employed comparative transcriptomics to analyze gene expression patterns across three age groups with progressively decreasing brain plasticity: native postnatal day seven brains, and young and old naïve and lesioned rat male brains. Analysis revealed a highly symmetrical distribution of upregulated and downregulated genes in postnatal day 7 brains. In contrast, the gene expression profiles of post-stroke brains exhibited significant asymmetry, with a disproportionate increase in upregulated genes compared to downregulated ones in both young and old post-ischemic brains. Gene variance in juvenile brains predominantly reflected processes associated with brain plasticity (e.g., Dcx, Tubb2b, Dok4, Dpysl5) and cell proliferation (e.g., Bex4). Conversely, gene expression variance in young and aged post-stroke brains was largely linked to inflammatory pathways, driven by cytokine and chemokine signaling. Notably, several genes specifically upregulated in aged brains were identified, including Ehd4, Fut7, Lilrb4, Plek, Slfn13, Slc14a1, and Smpdl3a. Immune genes that facilitate synaptic plasticity during early postnatal brain development-through processes such as pruning and sprouting to establish new connections in response to external stimuli-also contribute to post-stroke damage, confirming the concept of antagonistic pleiotropy. Our results suggest that targeting age-related immune responses could be an effective therapeutic strategy for stroke recovery.

01 Mar 2025·CNS Neuroscience & Therapeutics

Proteomic Analyses of Clots Identify Stroke Etiologies in Patients Undergoing Endovascular Therapy

Article

Author: Ko, Sang‐Bae ; Jung, Jin Woo ; Kim, Young‐Ju ; Kim, Tae Jung ; Yoon, Byung‐Woo ; Han, Dohyun

ABSTRACTAimsThis study aimed to investigate the correlation between clot composition and stroke mechanisms in patients undergoing endovascular therapy (EVT), using proteomic analysis.MethodsThis study included 35 patients with ischemic stroke (cardioembolism [CE], n = 17; large artery atherosclerosis [LAA], n = 6; cancer‐related [CR], n = 4; and undetermined (UD) cause, n = 8) who underwent EVT. Retrieved clots were proteomically analyzed to identify differentially expressed proteins associated with the three stroke mechanisms and to develop the machine learning model.ResultsIn the discover stage, 3838 proteins were identified using clot samples from 27 patients with CE, LAA, and CR mechanisms. Through functional enrichment and network analysis, 149 proteins were identified as potential candidates for verification studies. After verification experiments, 34 proteins were selected as the final candidates to predict stroke mechanisms. Furthermore, the machine learning‐based model identified three proteins associated with each mechanism (Pleckstrin in CE; CD59 glycoprotein in LAA; and Immunoglobulin Heavy Constant Gamma 1 in CR) in the UD group.ConclusionsThis study identified specific protein markers of clots that could differentiate stroke mechanisms in patients undergoing EVT. Therefore, our results could offer valuable insights into elucidating the mechanisms of ischemic stroke, which could provide information on more effective secondary prevention strategies.

20 Dec 2024·ACS Chemical Biology

Small Molecule Modulator of the mTORC2 Pathway Discovered from a DEL Library Designed to Bind to Pleckstrin Homology Domains

Article

Author: Gonse, Arthur ; Barluenga, Sofia ; Loewith, Robbie ; Daguer, Jean-Pierre ; Winssinger, Nicolas ; Gajić, Jelena

Pleckstrin homology (PH) domains are structural motifs critical for cellular processes, such as signal transduction and cytoskeletal organization. Due to their involvement in various diseases, PH domains are promising therapeutic targets, yet their highly charged and hydrophobic binding sites are not ideal for traditional small drugs. In this study, we designed a DNA-encoded library (DEL) mimicking phospholipids to identify novel modulators targeting PH domains with uncharted chemical properties. Screening against several PH domains led to the discovery of 2DII, a small molecule that selectively binds to mSin1^PH. This compound can modulate mTORC2 activity by impairing mTORC2's membrane interactions, resulting in reduced AKT1 phosphorylation. A micromapping via Dexter energy transfer based on 2DII bearing an iridium catalyst (2DII-Ir), along with a biotin-diazirine small molecule was used for target identification by proteomics, which confirmed mSin1 as the primary intracellular target of 2DII, demonstrating its potential for selective mTORC2 pathway modulation. These findings introduce a novel strategy for targeting PH domains and provide a foundation for the development of therapeutic interventions that modulate PH-domain-dependent signaling pathways.

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