- |||||||||| Tagrisso (osimertinib) / AstraZeneca
Journal: The effect of PLK1 inhibitor in osimertinib resistant non-small cell lung carcinoma cells. (Pubmed Central) - Oct 30, 2023
These findings enhance our understanding of ESCC pathogenesis and highlight promising avenues for treatment. PLK1 inhibitors have a synergistic effect with osimertinib on osimertinib-resistant NSCLC cells which indicates that they may have potential clinical value in the treatment of NSCLC patients with osimertinib resistance.
- |||||||||| GSK461364 / GSK
Journal, Epigenetic controller: PLK1 Regulates MicroRNA Biogenesis through Drosha Phosphorylation. (Pubmed Central) - Oct 2, 2023
Small RNA sequencing and qPCR validation were used to assess downstream consequences of PLK1 activity on miR biogenesis, identifying a set of ten miRs (miR-1248, miR-1306-5p, miR-2277-5p, miR-29c-5p, miR-93-3p, miR-152-3p, miR-509-3-5p, miR-511-5p, miR-891a-5p and miR-892a) whose expression levels were statistically significantly downregulated by two pharmacological PLK1 kinase domain inhibitors, RO-5203280 and GSK461364...In combination with prior studies, this work identifies Drosha S and S as major integration points for signalling by several kinases, whose relative activities will determine the relative biogenesis efficiency of different miR subsets. Identified kinase-regulated miRs have potential for use as kinase inhibitor response-predictive biomarkers, in cancer and other diseases.
- |||||||||| BI2536 / Boehringer Ingelheim, GSK461364 / GSK
Journal: A polo-like kinase inhibitor identified by computational repositioning attenuates pulmonary fibrosis. (Pubmed Central) - Jun 7, 2023
These findings suggest that targeting PLK1 may be a novel therapeutic approach for pulmonary fibrosis by inhibiting lung fibroblast proliferation without affecting lung epithelial cells. In addition, while in silico screening is useful, it is essential to fully determine the biological activities of candidates by wet-lab validation studies.
- |||||||||| adavosertib (AZD1775) / AstraZeneca, GSK461364 / GSK
3D cell-culture strategy for screening novel agents in Fanconi anemia chemoprevention (Section 27; Poster Board #26) - Mar 14, 2023 - Abstract #AACR2023AACR_7636;
Differentiation was indicated by upregulation panKeratin and Transglutaminase-3. We conclude combination therapies with high interest agents in FA-associated oral cancer can be performed in 3D culture systems and might confirm drug mechanisms of action, thus augmenting other standard methods of cancer drug evaluation and screening (e.g. cell proliferation and clonogenicity).
- |||||||||| tirbanibulin oral (KX2-391 oral) / Hanmi, Athenex, GSK461364 / GSK
Biomarker, Retrospective data, Journal, IO biomarker: Definition of a Novel Cuproptosis-Relevant lncRNA Signature for Uncovering Distinct Survival, Genomic Alterations, and Treatment Implications in Lung Adenocarcinoma. (Pubmed Central) - Oct 26, 2022
We also predicted several small molecule compounds (GSK461364, KX2-391, etc.) for treating this subset. Accordingly, this cuproptosis-relevant lncRNA signature offers an efficient approach to identify and characterize diverse prognosis, genomic alterations, and treatment outcomes in LUAD, thus potentially assisting personalized therapy.
- |||||||||| prexasertib (ACR-368) / Acrivon Therap, cofetuzumab pelidotin (ABBV-647) / Pfizer, AbbVie, GSK461364 / GSK
Journal: Multiomics characterization implicates PTK7 in ovarian cancer EMT and cell plasticity and offers strategies for therapeutic intervention. (Pubmed Central) - Aug 22, 2022
Furthermore, using high-throughput drug sensitivity testing (525 drugs) we show that targeting PTK7 exhibited synergistic activity with chemotherapeutic agent paclitaxel, CHK1/2 inhibitor prexasertib, and PLK1 inhibitor GSK461364, among others, in OC cells and ex vivo primary samples. Taken together, our study provides unique insight into the function of PTK7, which helps to define its role in mediating aberrant Wnt signaling in ovarian cancer.
- |||||||||| BI2536 / Boehringer Ingelheim, GSK461364 / GSK
Computational drug repositioning and wet-lab validation approach identifies polo-like kinase inhibitors as potential therapeutics for pulmonary fibrosis (TP-6 in thematic poster area) - Jun 22, 2022 - Abstract #ERS2022ERS_2380;
The experimental lung fibrosis was induced in mice by bronchial administration of bleomycin...[Results] Computational drug repositioning predicted that BI2536, a polo-like kinase (PLK) 1/2 inhibitor as a new therapeutic agent for IPF...Because the immunofluorescence staining revealed that PLK1 expression was dominant in myofibroblasts, while PLK2 expression was dominant in lung epithelial cells, we next focused on GSK461364, selective PLK1 inhibitor...[Conclusion] Targeting PLK1 may be a novel therapeutic approach for pulmonary fibrosis. In addition, while in silico screening is useful, it is essential to determine the biological activities of candidates by wet-lab validation studies.
- |||||||||| GSK461364 / GSK, galeterone (TOK-001) / Eledon
Journal: Recent advancements on Benzimidazole: A versatile scaffold in medicinal chemistry. (Pubmed Central) - Apr 7, 2022
A number of benzimidazoles such as bendamustine, pantoprazole have been approved for the treatment of various illnesses whereas galeterone and GSK461364 are in clinical trials. The present review article gives an overview about the different biological activities exhibited by the benzimidazole derivatives as well as different methods used for the synthesis of benzimidazole derivatives for the past ten years.
- |||||||||| BI2536 / Boehringer Ingelheim, GSK461364 / GSK
Computational Drug Repositioning Approach Identifies Polo-Like Kinase Inhibitors as Potential Therapeutics for Pulmonary Fibrosis (Area D, Hall F (North Building, Exhibition Level), Moscone Center) - Feb 19, 2022 - Abstract #ATS2022ATS_1572;
On the other hand, GSK461364, selective PLK1 inhibitor, attenuated pulmonary fibrosis with acceptable mortality and weight loss...[Conclusion] These findings indicate that the targeting PLK1 may be a novel therapeutic approach for pulmonary fibrosis by inhibiting fibroblast proliferation without affecting epithelial cells. In addition, the computational approaches leveraging public gene expression data may be a useful method to find a novel antifibrotics.
- |||||||||| adavosertib (AZD1775) / AstraZeneca, GSK461364 / GSK
[VIRTUAL] Use of kinase inhibitors in Fanconi anemia oral cancercell lines () - Mar 11, 2021 - Abstract #AACR2021AACR_1563;
Our current data demonstrate feasibility and preclinical efficacy of a combined agent approach for FA associated head and neck cancer. The low reported toxicity of these agents clinically allows for all of these agents to potentially move forward clinically, once additional experiments are conducted in mechanistic and animal studies.
- |||||||||| paclitaxel / Generic mfg.
Journal: Polo-like kinase 1 (Plk1) inhibition synergizes with taxanes in triple negative breast cancer. (Pubmed Central) - Apr 10, 2020
Inhibition of Plk1 in combination with taxanes shows promising results in a subset of triple negative breast cancer intrinsically resistant to chemotherapy. Onvansertib showed significant tumor volume shrinkage when combined with paclitaxel in vivo and should be considered in clinical trials for the treatment of triple negative cancers.
- |||||||||| doxorubicin hydrochloride / Generic mfg.
Journal: Doxorubicin as a fluorescent reporter identifies novel MRP1 (ABCC1) inhibitors missed by calcein-based high content screening of anticancer agents. (Pubmed Central) - Feb 7, 2020
Six drugs (afatinib, celecoxib, doramapimod, mifepristone, MK-2206 and rosiglitazone) were evaluated for their ability to reverse resistance of MRP1-overexpressing H69AR lung cancer cells against vincristine, doxorubicin and etoposide...Anti-cancer agents that exhibit MRP1 inhibition may be used to reverse multidrug resistance or to improve the efficacy and reduce the toxicity of various cancer chemotherapies. On the other hand, anti-cancer drugs that did not interact with MRP1 carry a low risk for developing MRP1-mediated resistance.
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