Last update 01 Nov 2024

PI3K family x HSP90

Last update 01 Nov 2024

Basic Info

Related Targets

PI3K familyHSP90

Drugs associated with PI3K family x HSP90

HSP90-PI3K conjugates(SciClone Pharmaceuticals (Holdings) Ltd.)

Target

HSP90 x PI3K family

Mechanism

HSP90 inhibitors [+1]

Active Org.

SciClone Pharmaceuticals (Holdings) Ltd.

Originator Org.

SciClone Pharmaceuticals (Holdings) Ltd.

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

T-2143

Target

HSP90 x PI3K family

Mechanism

HSP90 inhibitors [+1]

Active Org.-

Originator Org.

Tarveda Therapeutics, Inc.

Active Indication-

Inactive Indication

Solid tumor

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PI3K family x HSP90

100 Translational Medicine associated with PI3K family x HSP90

0 Patents (Medical) associated with PI3K family x HSP90

482

Literatures (Medical) associated with PI3K family x HSP90

01 Jan 2025·Journal of Ethnopharmacology

Revealing the molecular mechanism of baohuoside I for the treatment of breast cancer based on network pharmacology and molecular docking

Article

Author: Xiao, Yujie ; Hu, Min ; He, Xiao ; Yiling, Ding ; Mu, Junjie ; Xiao, He ; Pengyang, Song ; Chen, Qiuxiong ; Song, Pengyang ; Zhang, Xue ; He, Ziyue ; Zeng, Jun ; Li, Ying ; Yang, Xian ; Ding, Yiling

ETHNOPHARMACOLOGICAL RELEVANCEIn Traditional Chinese Medicine (TCM), there are many prescriptions for treating breast cancer (BC) that utilize the herb Epimedium brevicornum Maxim, which warms and replenishes kidney yang. Baohuoside I (BI) is a flavonoid compound found in Epimedium brevicornum Maxim. As a single glycoside, it is not easily hydrolyzed in the intestine and is typically absorbed as a precursor. As a natural product with potential anti-cancer properties, studies have shown that BI possesses anti-cancer activity and can inhibit the invasion and migration of BC cells. However, its underlying mechanisms remain unclear, thus further research is needed to validate its modern mechanisms for traditional uses.AIM OF THE STUDYThis study aimed to explore the regulatory mechanism of BI in the signaling pathways of BC cells through network pharmacology (NP), molecular docking (MD) techniques and cellular experiments.METHODSPotential targets were predicted using public databases, and a protein-protein interaction (PPI) network was constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Key signaling pathways were validated through MD techniques, cellular experiments, RNA interference and Western blot (WB) analysis.RESULTSTreatment-associated targets included SRC, MAPK1, HSP90AA1, PIK3CA, TP53, AKT1, and EGFR. GO enrichment, KEGG enrichment analyses, and MD results indicated that BI exerts its anti-breast cancer effects by inhibiting the tyrosine kinase activity of EGFR, as well as through downstream MAPK signaling pathway and PI3K-Akt signaling pathway pathways. In vitro experiments confirmed that BI primarily induce cell apoptosis through the EGFR-mediated MAPK signaling pathway and PI3K-Akt signaling pathway.CONCLUSIONBI can inhibit EGFR activation and promote BC cell apoptosis through the MAPK signaling pathway and PI3K-Akt signaling pathway, thereby exerting therapeutic effects on BC. This study not only provides experimental evidence for the accuracy of NP but also offers an effective approach for rational utilization of Baohuoside I-like flavonoid compounds as anti-breast cancer drugs.

01 Dec 2024·Current Pharmaceutical Design

Integrating Network Pharmacology, Bioinformatics, and Mendelian Randomization Analysis to Identify Hub Targets and Mechanisms of Kunkui Baoshen Decoction in Treating Diabetic Kidney Disease

Article

Author: Yu, Jiangyi ; Song, Siyuan

Objective:To uncover the potential hub targets of Kunkui Baoshen Decoction (KKBS) in alleviating Diabetic Kidney Disease (DKD).Methods:Targets associated with KKBS and DKD were curated from TCMSP, GeneCards, OMIM, and Dis- GeNET databases. Common targets were identified through intersection analysis using a Venn diagram. Employing the "Drug-component-target" approach and constructing a Protein-protein Interaction (PPI) network, pivotal components and hub targets involved in KKBS's therapeutic action against DKD were identified. Functional enrichment and Gene Set Enrichment Analysis (GSEA) elucidated the potential mechanisms of these hub targets. Molecular docking simulations validated binding interactions. Subsequently, hub targets were validated using independent cohorts and clinical datasets. Immune cell infiltration in DKD samples was assessed using ESTIMATE, CIBERSORT, and IPS algorithms. A nomogram was developed to predict DKD prevalence. Finally, causal relationships between hub targets and DKD were explored through Mendelian randomization (MR) analysis at the genetic level.Results:Jaranol, isorhamnetin, nobiletin, calycosin, and quercetin emerged as principal effective components in KKBS, with predicted modulation of the PI3K/Akt, MAPK, HIF-1, NF-kB, and IL-17 signaling pathways. The hub targets in the PPI network include proteins involved in regulating podocyte autophagy and apoptosis, managing antioxidant stress, contributing to insulin resistance, and participating in extracellular matrix deposition in DKD. Molecular docking affirmed favorable binding interactions between principal components and hub targets. Validation efforts across cohorts and databases underscored the potential of hub targets as DKD biomarkers. Among 20 model algorithms, the Extra Tree model yielded the largest Area Under the Curve (AUC) in receiver operating characteristic (ROC) analysis. MR analysis elucidated that the targets related to antioxidant stress had a positive impact on DKD, while the target associated with renal tubular basement membrane degradation had a negative impact.Conclusion:Integration of Network Pharmacology, Bioinformatics, and MR analysis unveiled the capacity of KKBS to modulate pivotal targets in the treatment of DKD.

01 Dec 2024·International Immunopharmacology

Bioinformatics data combined with single-cell analysis reveals patterns of immunoinflammatory infiltration and cell death in melanoma

Article

Author: Cui, Fan ; Liu, Yangying ; Rang, Zhen ; Yang, Ge ; Jin, Li

BACKGRUONDMelanoma is a common cancer in dermatology, but its molecular mechanisms remain poorly explained.AIMUtilizing single-cell analytics and bioinformatics, the work sought to discover the immunological infiltration and cellular molecular mechanisms of melanoma.METHODSMelanoma genes databases were downloaded from GeneCards, and gene expression profiles were chosen from the Gene Expression Omnibus (GSE244889). Establishing and analyzing protein-protein interaction networks for functional enrichment made use of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases. The process assesses the immunological cell infiltration variations between normal and malignant samples by Immune Cell AI software program. Different cell type differences were clarified by cell quality control, filtration, removal of batch effects and cell clustering analysis using single cell analysis techniques.RESULTSUsing a variety of machine learning techniques, 20 differentially expressed hub genes were found; among these, TP53, HSP90AB1, HSPA4, RHOA, CCND1, CYCS, PPARG, NFKBIA, CAV1, ANXA5, ENO1, ITGAM, YWHAZ, RELA, SOD1, and VDAC1 were found to be significantly significant. The results of enrichment analysis demonstrated that immune response and inflammatory response were strongly associated with melanoma. Animal mitophagy, ferroptosis, the PI3K-Akt signaling pathway, and the HIF-1 signaling pathway were the primary signaling pathways implicated. Cells of immunity, T-cells, lymphocytes, B-cells, NK-cells, monocytes, and macrophages were shown to be significantly infiltrated in melanoma patients, according to analysis. Single cell analysis also demonstrated that ferroptosis is a significant mechanism of cell death that contributes to the advancement of melanoma and that macrophages are important in the disease.CONCLUSIONIn summary, different immune cell infiltrations-particularly macrophages-have a significant impact on the onset and course of melanoma, and our findings may help direct future investigations into melanoma macrophages.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis