A Phase 1, First in Man, Dual Centre, Open-label Dose Escalation Study With Expansion to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CCT3833 (BAL3833), a panRAF Inhibitor, Given Orally in Patients With Advanced Solid Tumours, Including Metastatic Melanoma

The study is a first in man, dose escalation study to evaluate the safety, tolerability and how the drug works in the body in patients with all solid tumours. The aim of this study is to determine the most effective dose of the study drug that can then be further investigated in patients with advanced melanoma.

Start Date15 Apr 2015

Sponsor / Collaborator

Royal Marsden NHS Foundation Trust

[+2]

100 Clinical Results associated with SRC x Raf kinase

100 Translational Medicine associated with SRC x Raf kinase

0 Patents (Medical) associated with SRC x Raf kinase

546

Literatures (Medical) associated with SRC x Raf kinase

01 Jul 2025·Brain Research

Effects of Asiatic acid on brain cancer by altering astrocytes and the AKT1-PRKCB signaling pathway: A genomic and network pharmacology perspective

Article

Author: Kumar Mishra, Sunil ; Singh, Amit Kumar ; Agrawal, Shreni ; Tiwari, Kavindra Nath ; Kumar, Pradeep ; Kumar Pathak, Adarsh ; Kumar Sah Gond, Manjeet ; Kumar Singh, Anand ; Singh Negi, Rohit ; Das, Richa

The most common primary brain tumor, glioblastoma (GBM), currently has a dismal prognosis because of its fast growth and dissemination. Recent research indicates that Asiatic acid (AA), which is extracted from Trema orientalis L., has potential as a medicinal agent. AA, which was obtained from a methanolic extract of Trema orientalis L. and examined utilizing high-resolution mass spectroscopy (HRMS) analysis, was employed in this investigation. Then, in order to forecast the therapeutic advantages of AA in managing GBM, we conducted an in silico study. Online web servers like SwissADME, pKCSM, and Protox-II were used to assess AA. Then, the major targets of the AA (from Swiss Target Prediction and TargetNet) and GBM (from GeneCards and DisGeNET) were identified. The important genes were then merged into the STRING and ShinyGo databases to examine the protein-protein interaction (PPI) network, gene annotation, and KEGG pathways, with the goal of identifying the core mechanisms involved in GBM management. The top five hub gene targets of the built network (AKT1, SRC, IL-6, TNF, and EGFR) were investigated, along with some contemporaneous additional major targets (PRKCB, GSK3B, ITGB1, BRAF, and PTPN6). These targets were tightly linked to GO activities such as synoviocyte proliferation, cytokine activity, and EGFR tyrosine kinase inhibitor resistance, as well as proteoglycans in cancer-related pathways. Furthermore, a survival study was conducted to assess the chronicity of targets, as well as molecular docking activity between important targets and AA against GBM to determine binding effectiveness. Overall, the study found that AKT1 is the most powerful receptor for AA, having a binding energy of -8.19 kcal/mol, followed by PRKCB (-7.53 kcal/mol). Finally, docking studies suggest that AA has the potential to be an effective treatment for GBM. Furthermore, clinical studies will provide more precise insights into the AA's efficacy as a medicine in the future.

01 May 2025·Toxicology

A network toxicology and molecular docking-based approach revealed shared hepatotoxic mechanisms and targets between the herbicide 2,4-D and its metabolite 2,4-DCP

Article

Author: Gomes, Cleyton ; Farias, Davi ; Martins, Rafael Xavier ; Souza, Juliana Alves da Costa Ribeiro ; Carvalho, Matheus ; Souza, Terezinha

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and its major environmental metabolite 2,4-dichlorophenol (2,4-DCP) are pollutants associated with hepatotoxicity, whose molecular mechanisms remain poorly understood. This study investigated the molecular pathways and targets involved in 2,4-D and 2,4-DCP-induced hepatotoxicity using protein-protein interaction (PPI) network analyses and molecular docking. Target genes were identified using PharmMapper and SwissTargetPrediction, and cross-referenced with hepatotoxicity-related genes from GeneCards and OMIM databases. The PPI network, constructed via STRING and visualized in Cytoscape, revealed 12 critical hub nodes, including HSP90AA1, RXRA, EGFR, SRC, CREBBP, PIK3R1, ESR1, AKT1, RAF1, IGF1R, MDM2, and MAPK14. Gene Ontology (GO) analysis indicated processes such as apoptosis, oxidative stress, mitochondrial dysfunction, and lipid metabolism impairment, while Reactome pathway analysis highlighted disruptions in PI3K/AKT and nuclear receptors signaling. Molecular docking confirmed significant interactions of 2,4-D and 2,4-DCP with key proteins, including SRC, AKT, RXRA, MDM2, and HSP90AA1. These results suggest that 2,4-D and 2,4-DCP share similar toxic mechanisms, providing new insights into their hepatotoxicity pathways for the first time.

08 Nov 2024·Medicine

Network pharmacology and molecular docking to explore the potential molecular mechanism of chlorogenic acid treatment of oral squamous cell carcinoma

Article

Author: Hao, Puyu ; Xve, Xulong ; Zhang, Jun ; Yang, Yutao ; Feng, Zhanqin

Oral squamous cell carcinoma (OSCC) is a tumor type with a high mortality rate. Chlorogenic acid, abundant in resources and widely utilized in cancer treatments, has seen limited studies regarding its efficacy against OSCC. This paper investigates chlorogenic acid’s mechanism in treating OSCC, aiming to guide the development of novel drugs. The study employed network pharmacology, molecular docking, and survival analysis methods. Network pharmacological analysis revealed chlorogenic acid targets 23 OSCC-related proteins, including ESR1, MMP2, MMP9, SRC, MAPK8, MAPK1, CDC42, ERBB2, ATM, and BRAF. Molecular docking simulations indicated that the primary target exhibits significant binding capacity with chlorogenic acid, with MMP9 associated with tumor migration and angiogenesis standing out. Survival analysis demonstrated that the downregulation of most primary targets correlates with improved survival rates in OSCC patients. Enrichment analysis of therapeutic targets highlighted the pivotal role of MAPK-ERK and MAPK-JNK signaling pathways in chlorogenic acid’s efficacy against OSCC. This paper predicts chlorogenic acid’s potential targets and proposes its molecular mechanism in treating OSCC, offering a theoretical foundation for its application in OSCC treatment. We used traditional Chinese medicine, a disease pharmacology-related information base, and an analysis platform to predict targets. The Cytoscape 3.9.1 and STING databases were used to address common targets for drugs and diseases, establish networks of protein interaction relationships, and screen core targets. Meastro11.5 was used for molecular docking simulation. R4.2.2 was used for survival analysis and joint target enrichment analysis. Network pharmacological analysis identified chlorogenic acid acting on 23 OSCC targets. Molecular docking simulations revealed a strong binding affinity of chlorogenic acid compounds with these targets, particularly MMP9, essential for tumor migration and angiogenesis. Survival analysis indicated that the downregulation of most core targets was correlated with improved OSCC patient survival. Enrichment analysis of therapeutic targets highlighted the critical roles of the MAPK-ERK and MAPK-JNK signaling pathways in the effectiveness of chlorogenic acid against OSCC. This study predicted the potential targets of chlorogenic acid in OSCC treatment and hypothesized its molecular mechanism, offering a theoretical foundation for its use in OSCC therapy.

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