Delving into the Latest Updates on Telatinib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Telatinib mesylate

Target

PDGFRβ x VEGFR2 x VEGFR3 x c-Kit

Mechanism

PDGFRβ inhibitors(Platelet-derived growth factor receptor beta inhibitors), VEGFR2 antagonists(Vascular endothelial growth factor receptor 2 antagonists), VEGFR3 antagonists(Vascular endothelial growth factor receptor 3 antagonists)

+ [1]

Therapeutic Areas

NeoplasmsDigestive System Disorders

Active Indication

Advanced gastric carcinoma

Inactive Indication

Advanced Malignant Solid NeoplasmColorectal CancerEsophageal Carcinoma+ [2]

Originator Organization

Bayer AG

Active Organization

EOC Pharma (Thaizhou) Co., Ltd.

Inactive Organization

Eddingpharm (Cayman), Inc.

ACT Biotech, Inc.

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (US)

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Structure/Sequence

Molecular FormulaC20H16ClN5O3

InChIKeyQFCXANHHBCGMAS-UHFFFAOYSA-N

CAS Registry332012-40-5

The purpose of the trial is to compare the combination regimen of Telatinib and Capecitabine and Oxaliplatin vs. Capecitabine and Oxaplatin to explore superiority of the Telatinib combination in terms of progression-free survival (PFS) in patients previously untreated for advanced HER2 negative advanced gastric or Gastroesophageal Junction adenocarcinoma.

Start Date25 Jan 2019

Sponsor / Collaborator

EOC Pharma (Thaizhou) Co., Ltd.

[+2]

100 Clinical Results associated with Telatinib

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100 Translational Medicine associated with Telatinib

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100 Patents (Medical) associated with Telatinib

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20

Literatures (Medical) associated with Telatinib

23 Sep 2024·Current Medicinal Chemistry

Discovery of Small Molecule Inhibitors Targeting CTNNB1 (β-catenin) for Endometrial cancer: Employing 3D QSAR, Drug-Likeness Assessment, ADMET Predictions, Molecular Docking and Simulation

Article

Author: Liao, Mingzhi ; Fatima, Israr ; He, Zhijie ; Rehman, Abdur ; Wang, Peng

Background:Endometrial carcinoma (EC) is a type of cancer that originates in the lining of the uterus, known as the endometrium. It is associated with various treatment options such as surgery, radiation therapy, chemotherapy, and hormone therapy, each presenting unique challenges and limitations. Beta-catenin, a protein involved in the development and progression of several cancers, including EC, plays a crucial role. Abnormal beta-catenin signaling is often linked to the emergence of specific EC subtypes, affecting tumor growth and invasion.Objectives:The study's objective is to identify compounds targeting the beta-catenin protein for treating endometrial cancer (EC) using in silico drug design. Our approach includes molecular docking to evaluate binding affinities, ADME profiling for pharmacokinetic properties, toxicity assessments, and molecular dynamics simulations to assess compound stability and interactions.Methods:Approximately one thousand anti-cancer phytochemicals were sourced from PubChem and subjected to molecular docking simulations against the beta-catenin protein. The compounds were evaluated based on their binding affinities, with the top five selected for further analysis. These five molecules underwent toxicity and ADME profiling. The Prediction of Activity Spectra for Substances (PASS) tool was used to identify compounds targeting CTNNB1. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were employed to establish quantitative structure-activity relationship (QSAR) models for the five CTNNB1 antagonist molecules.Results:The selected five compounds, namely Pazopanib, Binimetinib, Telatinib, 4-(2,3-Dihydrobenzo[ b][1,4]dioxin-6-yl)-3-((5-nitrothiazol-2-yl)thio)-1H-1,2,4-triazol-5(4H)-one, and Ribavirin, demonstrated efficacy against CTNN1. MD simulations of the docked complexes confirmed the stability of these drugs in binding to the target protein. All five molecules showed promising safety and effectiveness profiles according to their ADME and toxicity evaluations.Conclusion:Through a comprehensive screening process employing in silico drug design methods, this study successfully identified five potential human anticancer drug candidates targeting the beta-catenin protein. These findings offer a foundation for further experimental validation and development towards the treatment of EC.

18 Sep 2024·Discover oncology

Analysis of the role of CHPF in colorectal cancer tumorigenesis and immunotherapy based on bioinformatics and experiments.

Article

Author: Shi, Yexin ; Wu, Jingyu ; Zhao, Qinghong ; Ma, Xiang ; Wang, Zijun ; Xia, Qingcheng ; Wang, Pengchao ; Song, Qingyu ; Lu, Ming

BACKGROUNDChondroitin polymerizing factor (CHPF) has been found to be involved in the development of numerous cancers and correlated with poor prognosis. However, its role in the tumorigenesis and development of colorectal cancer (CRC) remains unknown.METHODSIn our research, we explored CHPF expression and clinicopathological characteristics using The Cancer Genome Atlas Program (TCGA), UALCAN, GSE9348, TIMER2.0 and The Human Protein Atlas (HPA) database, in addition, we validated CHPF expression in CRC cell lines by Real-Time Quantitative PCR (qRT-PCR) and Western blot (WB). KM-Plotter, PrognoScan and TCGA were also utilized to verify its prognosis value in CRC. Small-interfer RNA (Si-RNA) was used to perform Cell Counting Kit-8 (CCK8), colony formation, 5-ethynyl-2'-deoxyuridine (EDU), transwell and wound healing assays to testify its function on the tumor progression. Based on TCGA database, we probed potential biological mechanism by which CHPF play its role via clusterProfiler package and GEPIA database and we validated their correlation by WB assay. Moreover, we explored its potential association with the tumor microenvironment (TME), immune infiltrated cells, immune checkpoints, tumor mutation burden (TMB) as well as microsatellite instability (MSI), and investigated immunotherapy sensitivity via Tumor Immune Dysfunction and Exclusion (TIDE) algorithm as well as potentially effective therapeutic drugs via pRRophetic algorithm.RESULTSCHPF was identified upregulated in CRC tissues and cells, correlated with poor prognosis, and nodal metastasis status, stage and histological subtype. Down-regulation of CHPF inhibited CRC cell proliferation, migration and its expression correlated with wnt pathway key molecules. In addition, high expression of CHPF was positively correlated with TME scores, Regulatory T cells (Tregs) cell infiltration degree, Programmed death-1 (PD-1), MSI-high (MSI-H), and TIDE scores, however, not with TMB. Targeted drug analysis showed that patients with high CHPF expression were more sensitive to telatinib, recaparib, serdemetan, and trametinib.CONCLUSIONCHPF could promote the proliferation and migration of CRC cells and lead to poor prognosis, possibly through wnt pathways as well as changes in TME. Patients with high expression of CHPF had poor efficacy in immunotherapy, which might be related to Tregs cell infiltration. Above all, it might offer more reliable guidance for future immunotherapy.

01 Jun 2018·Clinical Cancer ResearchQ1 · MEDICINE

Telatinib Is an Effective Targeted Therapy for Pseudomyogenic Hemangioendothelioma

Q1 · MEDICINE

Article

Author: Szuhai, Karoly ; Sleijfer, Stefan ; Bovée, Judith V.M.G. ; van IJzendoorn, David G.P. ; Eskens, Ferry A.L.M. ; Gelderblom, Hans ; van Leenders, Geert J.L.H.

AbstractPurpose: Pseudomyogenic hemangioendothelioma (PHE) is an extremely rare locally aggressive neoplasm with endothelial differentiation, which often presents with multiple lesions. These tumors have characteristic SERPINE1–FOSB fusions. We report a 17 years old patient with advanced unresectable PHE with a durable complete remission to the multi-tyrosine kinase inhibitor telatinib. The aim of this study was to generate an in vitro model for PHE, to study the functional consequences of SERPINE1–FOSB in endothelial cells, and its interaction with telatinib, to biologically substantiate the complete response to telatinib.Experimental Design: As the fusion results in overexpression of a truncated form of FOSB, we overexpressed truncated FOSB in normal endothelial cells.Results: Truncated FOSB significantly affected tumor growth in three-dimensional (3D) on matrigel with increased and sustained sprouting. Moreover, truncated FOSB acted as an active transcription factor capable to regulate its own transcription, as well as to upregulate PDGFRA and FLT1 expression (four-fold). Telatinib decreased proliferation and tumor growth in 3D and induced apoptosis. As expected, telatinib blocked VEGF signaling as phosphorylation of ERK was abolished. Interestingly, in FOSB overexpressing cells, telatinib specifically affected PDGFRA, FLT1, and FLT4 signaling and downregulated SERPINE1, thereby affecting the self-regulation of the fusion gene.Conclusions: We provide a biological substantiation of a complete clinical remission that was seen in a patient with PHE, showing that telatinib indirectly interferes with the self-regulated expression of the fusion product. Thus, telatinib or any other currently available VEGFR1-4/PDGFRA inhibitor could be a highly specific treatment option for patients with multifocal unresectable PHE. Clin Cancer Res; 24(11); 2678–87. ©2018 AACR.

100 Deals associated with Telatinib

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15393

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Esophageal Carcinoma	Phase 1	US	-	15 Jul 2021
Liver Cancer	Phase 1	US	-	13 Jul 2021
HER2 negative Gastroesophageal Junction Adenocarcinoma	Phase 1	CN	EOC Pharma (Thaizhou) Co., Ltd.	25 Jan 2019
Advanced Malignant Solid Neoplasm	Phase 1	CN	EOC Pharma (Thaizhou) Co., Ltd.	25 Jul 2017
Stomach Cancer	Phase 1	ES	Eddingpharm (Cayman), Inc.	08 Jan 2014
Stomach Cancer	Phase 1	US	Eddingpharm (Cayman), Inc.	08 Jan 2014
Advanced gastric carcinoma	Phase 1	US	ACT Biotech, Inc.	01 Jun 2009
Advanced gastric carcinoma	Phase 1	ES	ACT Biotech, Inc.	01 Jun 2009
Colorectal Cancer	Phase 1	US	ACT Biotech, Inc.	07 May 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04798781 (CTgov)	Phase 2	Hepatocellular Carcinoma \| Advanced Gastroesophageal Junction Adenocarcinoma	16	Telatinib+keytruda	(cuvivwzhwb) = qqifmktyqh shpsiwhzvd (tbjxnsoril, gvwzflbiyw - sbuaomenay) View more	-	10 Oct 2024
NCT03175497 (ASCO 12019 \| ASCO 22019) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	15	telatinib	(lfsexbyldx) = 2 (hospitalization due to high blood pressure) dyvkrjdytj (opkgpivokc ) View more	Positive	01 Jun 2019
TEL0805 (ASCO2011)	Phase 2	Gastrooesophageal junction cancer First line	48	Telatinib + Capecitabine + Cisplatin	(kzhtldtlju) = bsqlwlwqye rrbvkiqyiq (eqauooxsbh ) View more	-	20 May 2011
TEL0805 (ASCO_GI2011)	Phase 2	Stomach Cancer	-	Telatinib + capecitabine (X) and cisplatin (P)	(zfwcbdrkom) = gdsooujrjl lirlxzmido (dfdtlxltsu )	-	01 Feb 2011
ASCO2010	Phase 2	Malignant neoplasm of gastro-oesophageal junction \| Stomach Cancer First line	19	Telatinib	(abbadxuovs) = vnylteojnn kyroapswwj (wjqwufmyoo )	-	20 May 2010