Small‐Molecule Inhibitors of Shp2 Phosphatase as Potential Chemotherapeutic Agents for Glioblastoma: A Minireview

Abstract

Glioblastoma multiforme (GBM) is a dreadful cancer characterised by poor prognosis, low survival rate and difficult clinical correlations. Several signalling pathways and molecular mediators are known to precipitate GBM, and small‐molecular targets of these mediators have become a favoured thrust area for researchers to develop potent anti‐GBM drugs. Shp2, an important phosphatase of the nonreceptor type protein tyrosine phosphatase (PTPN) subfamily is responsible for master regulation of several such signalling pathways in normal and glioma cells. Thus, inhibition of Shp2 is a logical strategy for the design and development of anti‐neoplastic drugs against GBM. Though tapping the full potential of Shp2 binding sites has been challenging, nevertheless, many synthetic and natural scaffolds have been documented as possessing potent and selective anti‐Shp2 activities in biochemical and cellular assays, through either active‐site or allosteric binding. Most of these scaffolds share a few common pharmacophoric features, a thorough study of which is useful in paving the way for the design and development of improved Shp2 inhibitors. This minireview summarizes the current scenario of potent small‐molecule Shp2 inhibitors and emphasizes the anti‐GBM potential of some important scaffolds that have shown promising GBM‐specific activity in in vitro and in vivo models, thus proving their efficacy in GBM therapy. This review could guide researchers to design new and improved anti‐Shp2 pharmacophores and develop them as anti‐GBM agents by employing GBM‐centric drug‐discovery protocols.

Comprehensive analysis of PTPN family expression and prognosis in acute myeloid leukemia

“…They are essential members of the protein tyrosine phosphatases family ( Tonks, 2006 ). Numerous studies have examined the relationships between specific PTPN family members and various neoplasms ( Chen et al, 2020 ; Mitra and Ayyannan, 2020 ). To date, no report has provided an overview of the connections between PTPN family genes and human leukemia.…”

Cell-Based Chemical Safety Assessment and Therapeutic Discovery Using Array-Based Sensors

“…Synthetic chemicals are widely used in agriculture [ 68 ], food [ 69 ] and medicine [ 70 ], raising concerns and fears regarding potential risks to human health. Current chemical safety assessment approaches generally focus on acute health outcomes as the endpoints for assessing the risks posed by chemical agents [ 71 ].…”

Ultrasmall iron oxide nanoparticles with MRgFUS for enhanced magnetic resonance imaging of orthotopic glioblastoma

“…Despite the development of modern therapies, survival rates remain low. 1 Surgical resection, external radiotherapy, 2 and chemotherapeutic agents 3–5 are still considered the best treatment approaches for GBM, and of which surgical intervention is the most effective treatment modality. 6 Yet, considering that GBMs are surrounded by infiltrating tumor cells that easily invade the surrounding tissue, it is not possible to entirely remove the tumor.…”