Akt-1 x TOP2A

Last update 08 May 2025

Basic Info

Related Targets

Akt-1TOP2A

Drugs associated with Akt-1 x TOP2A

NISC-6

Target

Akt-1 x TOP2A

Mechanism

AKT1 gene inhibitors [+1]

Active Org.

The Pennsylvania State University

Originator Org.

The Pennsylvania State University

Active Indication

Melanoma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with Akt-1 x TOP2A

100 Translational Medicine associated with Akt-1 x TOP2A

0 Patents (Medical) associated with Akt-1 x TOP2A

Literatures (Medical) associated with Akt-1 x TOP2A

01 Jan 2025·Translational Cancer Research

Exploration of key pathogenic mechanisms and potential intervention targets of the traditional Chinese medicine Coptis chinensis in the treatment of cervical cancer based on network pharmacology and molecular docking techniques

Article

Author: Li, Hequn ; Zhang, Lei ; Xu, Hui ; Sun, Jiaxing ; Jia, Hui ; Zhang, Renmin ; Hou, Ying

BackgroundTraditional Chinese medicine (TCM) has shown potential in the treatment of cancer. This study investigated the molecular targets and mechanisms of Coptis chinensis in the treatment of cervical cancer using network pharmacology and bioinformatics.MethodsEffective Coptis chinensis components were screened from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform based on the following criteria: drug-like properties (DLP) ≥0.18 and oral bioavailability (OB) ≥30%. Target genes were identified through DrugBank, while differentially expressed genes (DEGs) related to cervical cancer were sourced from the Gene Expression Omnibus (GEO) database (GSE7803) based on the following criteria: |log fold change| >2 and P<0.05. Common DEGs were identified through a Venn diagram analysis. The expression and prognostic relevance of the candidate genes were validated using The Cancer Genome Atlas (TCGA) database. Molecular docking was performed using Pubchem, Protein Data Bank (PDB), and CB-DOCK2. A gene set enrichment analysis (GSEA) was conducted to explore the potential mechanisms of DEGs. A retrospective analysis of cervical cancer patients (June 2021 to June 2022) was performed to examine the expression of key genes in the peripheral blood via enzyme-linked immunosorbent assay. A multivariate Cox regression was conducted to identify independent prognostic factors.ResultsIn total, 10 effective Coptis chinensis compounds and 181 target genes were identified from the TCMSP database. The GEO analysis of GSE7803 identified 109 DEGs. The Venn diagram analysis identified the following seven shared DEGs: AR, MAOB, CDKN2A, TOP2A, CXCL8, matrix metalloproteinase 1 (MMP1), and SPP1. MMP1 and SPP1 were confirmed to be upregulated candidate genes in cervical cancer tissues, and to be associated with a worse prognosis [overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI), P<0.05]. Molecular docking showed that MMP1 had high binding affinity with quercetin (-9.2) while that of SPP1 was lower (-6.3). The GSEA indicated that MMP1 was involved in the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), Janus kinase/signal transducer and activator of transcription (JAK/STAT), transforming growth factor-β (TGF-β), mitogen-activated protein kinase (MAPK), and hypoxia-inducible factor 1 (HIF1) pathways, and apoptosis. The retrospective analysis demonstrated that MMP1 expression was significantly decreased in the peripheral blood of patients receiving conventional chemotherapy and Coptis chinensis compared to those receiving chemotherapy alone. Multivariate Cox regression confirmed that high MMP1 expression and a lack of Coptis chinensis treatment were independent risk factors for a poor prognosis (P<0.05).ConclusionsMMP1 could be a predictive biomarker for cervical cancer. Coptis chinensis may exert therapeutic effects through MMP1 regulation via multiple pathways. Our findings provide a theoretical foundation for the clinical application of MMP1.

01 Dec 2024·Reproduction in Domestic Animals

Integrated Quantitative Proteomics and Phosphoproteomics Analysis Reveals the Dynamic Process of Buffalo (Bubalus bubalis) Spermatogenesis

Article

Author: Zhang, Pengfei ; Wang, Chenyang ; Zhang, Ming ; Fu, Qiang ; Pan, Limei ; Liu, Xuyang ; Huang, Yulin

ABSTRACTSpermatogenesis is a highly complex and tightly regulated cellular differentiation process closely related to the productive performance of male livestock. We do not yet have a clear understanding of the spermatogenesis mechanism of buffalo. In this study, spermatogonia, spermatocytes and spermatids were analysed by flow cytometry. Quantitative proteomic and phosphoproteomic studies were performed on different spermatogenic cells using tandem mass tagging technology and liquid chromatography–tandem mass spectrometry. A total of 219 differentially expressed proteins (involved in focal adhesions and actin cytoskeleton pathways) and 71 phosphoproteins (involved in RNA transport and adhesion junction pathways) were obtained. Through trend analysis, a dynamic profile of protein expression was obtained, enriched to the main biological processes at different stages of spermatogenesis. By immunohistochemical localisation analysis, it was found that MACROH2A2, TOP2A, LMNA, LMNA (pS392), VIM and VIM (pS56) had specific localisation in testis cells. Network analysis of kinase‐substrate phosphorylation sites showed that AKT1 is the most active kinase, LMNA is regulated by most kinases and AKT1 can catalyse the phosphorylation of LMNA. This study provides a reference for studying the molecular mechanism of buffalo spermatogenesis and helps clarify the regulatory mechanism of protein translation and post‐translational modification during mammalian spermatogenesis.

02 Dec 2022·Molecular Cancer Research

Molecular Profile Changes in Patients with Castrate-Resistant Prostate Cancer Pre- and Post-Abiraterone/Prednisone Treatment

Article

Author: Kohli, Manish ; Bhargava, Vipul ; Vedell, Peter T. ; Gormley, Michael ; Bryce, Alan H. ; Kalari, Krishna R. ; Tan, Winston ; Sinnwell, Jason P. ; Jimenez, Raphael E. ; Li, Ying ; Qin, Sisi ; Hillman, David W. ; Dehm, Scott M. ; Carlson, Rachel E. ; Weinshilboum, Richard M. ; Sicotte, Hugues ; Wang, Liewei

AbstractWe identified resistance mechanisms to abiraterone acetate/prednisone (AA/P) in patients with metastatic castration-resistant prostate cancer (mCRPC) in the Prostate Cancer Medically Optimized Genome-Enhanced Therapy (PROMOTE) study.We analyzed whole-exome sequencing (WES) and RNA-sequencing data from 83 patients with metastatic biopsies before (V1) and after 12 weeks of AA/P treatment (V2). Resistance was determined by time to treatment change (TTTC).At V2, 18 and 11 of 58 patients had either short-term (median 3.6 months; range 1.4–4.5) or long-term (median 29 months; range 23.5–41.7) responses, respectively. Nonresponders had low expression of TGFBR3 and increased activation of the Wnt pathway, cell cycle, upregulation of AR variants, both pre- and posttreatment, with further deletion of AR inhibitor CDK11B posttreatment. Deletion of androgen processing genes, HSD17B11, CYP19A1 were observed in nonresponders posttreatment. Genes involved in cell cycle, DNA repair, Wnt-signaling, and Aurora kinase pathways were differentially expressed between the responder and non-responder at V2. Activation of Wnt signaling in nonresponder and deactivation of MYC or its target genes in responders was detected via SCN loss, somatic mutations, and transcriptomics. Upregulation of genes in the AURKA pathway are consistent with the activation of MYC regulated genes in nonresponders. Several genes in the AKT1 axis had increased mutation rate in nonresponders. We also found evidence of resistance via PDCD1 overexpression in responders.Implications:Finally, we identified candidates drugs to reverse AA/P resistance: topoisomerase inhibitors and drugs targeting the cell cycle via the MYC/AURKA/AURKB/TOP2A and/or PI3K_AKT_MTOR pathways.

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