Last update 01 Nov 2024

Tubulin x EphA2

Last update 01 Nov 2024

Basic Info

Related Targets

TubulinEphA2

Drugs associated with Tubulin x EphA2

MEDI-547

Target

EphA2 x Tubulin

Mechanism

EphA2 modulators [+1]

Active Org.-

Originator Org.

MedImmune LLC

Active Indication-

Inactive Indication

Relapsed Solid Neoplasm

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

1C1-mcMMAF

Target

EphA2 x Tubulin

Mechanism

EphA2 antagonists [+1]

Active Org.-

Originator Org.-

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with Tubulin x EphA2

NCT00796055 / TerminatedPhase 1

A Phase 1, Open-Label Study of MEDI-547 to Evaluate the Safety, Tolerability, Pharmacokinetics, and Biologic Activity of Intravenous Administration in Subjects With Relapsed or Refractory Solid Tumors Associated With EphA2 Expression

To determine the safety, tolerability, and the highest dose of this drug given once every 3 weeks or once every week, (per 21 day cycle) in adult subjects with relapsed or refractory solid tumors.

Start Date01 Aug 2009

Sponsor / Collaborator

MedImmune LLC

100 Clinical Results associated with Tubulin x EphA2

100 Translational Medicine associated with Tubulin x EphA2

0 Patents (Medical) associated with Tubulin x EphA2

Literatures (Medical) associated with Tubulin x EphA2

01 Jan 2022·Clinical and Translational OncologyQ3 · MEDICINE

TRPS1 knockdown inhibits angiogenic vascular mimicry in human triple negative breast cancer cells

Q3 · MEDICINE

Article

Author: Wang, T ; Sun, X ; Li, P ; Wu, M ; Zhang, M

PURPOSEVascular mimicry (VM) tubules are lumen structures comprised of malignant tumor cells without the participation of endothelial cells. VM simulates blood vessel function in tumors to deliver a sufficient blood supply for proliferation, invasion, and metastasis of malignant tumors, thereby reducing the clinical effects of anti-angiogenic treatments. The elimination or prevention of malignant tumor VM development therefore represents an urgent research goal as a therapeutic strategy to and cut off nutrients required for tumor growth. The GATA transcription factor TRPS1 is abnormally up-regulated in breast cancer, osteosarcoma, prostate cancer, and other tumor tissues, and is instrumental in regulating cell proliferation, differentiation, and tissue growth and development.METHODSHere, we explored the effects of TRPS1 knockdown on VM and the proteins underlying its development in triple-negative breast cancer cell line MDA-MB-231.RESULTSWe found that TRPS1 knockdown resulted in obvious inhibition of VM development. Fluorescence microscopy of F-actin and tubulin revealed that loss of TRPS1 function resulted in disruption of cytoskeleton and microtubule formation, respectively. In addition, TRPS1-suppressed cells exhibited reduced accumulation of VM-associated proteins EphA2, MMP-2, MMP-9, VEGF, and VE-cadherin. Moreover, it is interesting to know that the capacity for migration and invasion were limited in MDA-MB-231cells after TRPS1 knockdown and that the average number of VM tubules, their length, and number of intersections were also significantly decreased.CONCLUSIONSBased on our results, and in light of previous studies, we thus proposed that TRPS1 suppression negatively affects vascular mimicry possibly through reduced TRPS1-mediated transcriptional regulation of VM-related protein VEGF-A.

01 Sep 2017·ELECTROPHORESISQ3 · BIOLOGY

Comparative membrane proteomics analyses of breast cancer cell lines to understand the molecular mechanism of breast cancer brain metastasis

Q3 · BIOLOGY

Article

Author: Zhu, Rui ; Mechref, Yehia ; Peng, Wenjing ; Zhang, Yu

AbstractBreast cancer is the leading type of cancer in women. Breast cancer brain metastasis is currently considered an issue of concern among breast cancer patients. Membrane proteins play important roles in breast cancer brain metastasis, involving cell adhesion and penetration of blood–brain barrier. To understand the mechanism of breast cancer brain metastasis, liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) was employed in conjunction with enrichment of membrane proteins to analyze the proteomes from five different breast cancer and a brain cancer cell lines. Quantitative proteomic data of all cell lines were compared with MDA‐MB‐231BR which is a brain seeking breast cancer cell line, thus representing brain metastasis characteristics. Label‐free proteomics of the six cell lines facilitates the identification of 1238 proteins and the quantification of 899 proteins of which more than 70% were membrane proteins. Unsupervised principal component analysis (PCA) of the label‐free proteomics data resulted in a distinct clustering of cell lines, suggesting quantitative differences in the expression of several proteins among the different cell lines. Unique protein expressions in 231BR were observed for 28 proteins. The up‐regulation of STAU1, AT1B3, NPM1, hnRNP Q, and hnRNP K and the down‐regulation of TUBB4B and TUBB5 were noted in 231BR relative to 231 (precursor cell lines from which 231BR is derived). These proteins might contribute to the breast cancer brain metastasis. Ingenuity pathway analysis (IPA) supported the great brain metastatic propensity of 231BR and suggested the importance of the up‐regulation of integrin proteins and down‐regulation of EPHA2 in brain metastasis.

CancersQ2 · MEDICINE

The Small Molecule Ephrin Receptor Inhibitor, GLPG1790, Reduces Renewal Capabilities of Cancer Stem Cells, Showing Anti-Tumour Efficacy on Preclinical Glioblastoma Models

Q2 · MEDICINE

ArticleOA

Author: Pujuguet, Philippe ; Festuccia, Claudio ; Sferra, Roberta ; Beirinckx, Filip ; Colapietro, Alessandro ; Mattei, Vincenzo ; Lorenzon, Giocondo ; Delle Monache, Simona ; Cristiano, Loredana ; Gravina, Giovanni Luca ; Martellucci, Stefano ; Mancini, Andrea ; Marampon, Francesco ; Vitale, Flora ; van der Aar, Ellen ; Saniere, Laurent

Therapies against glioblastoma (GBM) show a high percentage of failure associated with the survival of glioma stem cells (GSCs) that repopulate treated tumours. Forced differentiation of GSCs is a promising new approach in cancer treatment. Erythropoietin-producing hepatocellular (Eph) receptors drive tumourigenicity and stemness in GBM. We tested GLPG1790, a first small molecule with inhibition activity versus inhibitor of various Eph receptor kinases, in preclinical GBM models using in vitro and in vivo assays. GLPG1790 rapidly and persistently inhibited Ephrin-A1-mediated phosphorylation of Tyr588 and Ser897, completely blocking EphA2 receptor signalling. Similarly, this compound blocks the ephrin B2-mediated EphA3 and EphB4 tyrosine phosphorylation. This resulted in anti-glioma effects. GLPG1790 down-modulated the expression of mesenchymal markers CD44, Sox2, nestin, octamer-binding transcription factor 3/4 (Oct3/4), Nanog, CD90, and CD105, and up-regulated that of glial fibrillary acidic protein (GFAP) and pro-neural/neuronal markers, βIII tubulin, and neurofilaments. GLPG1790 reduced tumour growth in vivo. These effects were larger compared to radiation therapy (RT; U251 and T98G xenografts) and smaller than those of temozolomide (TMZ; U251 and U87MG cell models). By contrast, GLPG1790 showed effects that were higher than Radiotherapy (RT) and similar to Temozolomide (TMZ) in orthotopic U87MG and CSCs-5 models in terms of disease-free survival (DFS) and overall survival (OS). Further experiments were necessary to study possible interactions with radio- and chemotherapy. GLPG1790 demonstrated anti-tumor effects regulating both the differentiative status of Glioma Initiating Cells (GICs) and the quality of tumor microenvironment, translating into efficacy in aggressive GBM mouse models. Significant common molecular targets to radio and chemo therapy supported the combination use of GLPG1790 in ameliorative antiglioma therapy.

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