Small Molecules Identified by an In Silico Docking Screen Targeting Anaphase-Promoting Complex/Cyclosome Subunit 1 (APC1) Potentiate Paclitaxel-Induced Breast Cancer Cell Death

Molecules, Journal Year: 2025, Volume and Issue: 30(4), P. 895 - 895

Published: Feb. 14, 2025

Delaying mitotic cell cycle progression has been proposed as a strategy to potentiate the effects of anti-mitotic anti-cancer drugs that induce multipolar spindles. Toward this end, we have performed an in silico docking screen targeting anaphase-promoting complex/cyclosome subunit 1 (APC1) at conserved 10-amino acid surface site was modeled interact via single hydrogen bond with essential (APC/C) co-factor division 20 (CDC20). Five molecules were identified after screening 15,000 small molecules. As secondary cellulo bioactivity screening, MDA-MB-231 genomically unstable aneuploid breast cancer cells exposed each compound absence and presence 10 nM paclitaxel or eribulin, likely clinically relevant doses these cells. Two five compounds, which share common 2-(trifluoromethyl)quinazolin-4-amine chemical structure, induced elevated levels death combination paclitaxel, observed by fluorescence-activated sorting (FACS). These two compounds will now serve starting point for further optimization target validation experiments additional screens search other chemically related display more potent but specific effects.

Language: Английский

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Integrated Profiling Delineated KIF18A as a Significant Biomarker Associated with Both Prognostic Outcomes and Immune Response in Pancreatic Cancer

ImmunoTargets and Therapy, Journal Year: 2025, Volume and Issue: Volume 14, P. 123 - 138

Published: Feb. 1, 2025

Kinesin family member 18A (KIF18A) is a of the kinesin-8 motor proteins, involved in progression and metastasis various tumors. However, its role pancreatic adenocarcinoma (PAAD) remains unclear. To evaluate that role, RNA sequencing datasets, complemented by pertinent clinical metadata, were procured from Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) repositories. The protein expression level KIF18A PAAD was derived human atlas (HPA) database. differences levels prognostic related genes identified through multivariate Cox regression Lasso analysis to construct risk model. Tumor Mutation Burden (TMB), Microsatellite (MSI), immune landscape, mutation landscape drug sensitivity high- low-expression groups assessed immunotherapy cohorts cohorts. Finally, vitro experiments conducted elucidate molecular function regulating malignant behavior PAAD. highly expressed closely worse stage poor prognosis. Single cell revealed mainly microtubules tumor cells participated mitosis cycle Further TMB, MSI, infiltration. In confirmed promotes proliferation, migration adhesion molecules PAAD, inhibits angiogenesis. addition, high positively ferroptosis m6A expression, driven mutated KRAS TP53. This study can be used as marker predict prognosis it participates formation

Language: Английский

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Editorial for the Special Issue “Current Research on Cancer Biology and Therapeutics: 2nd Edition”

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11777 - 11777

Published: Nov. 2, 2024

In the second edition of this Special Issue, several promising antitumor strategies have been presented in addition to those reported first edition, which compounds (acetylcorynoline, BaP1, sarco/endoplasmic reticulum calcium ATPase inhibitors, neuropeptide Y, Y antagonists, neurokinin-1 receptor antagonists) exerting effects against colorectal cancer, papillary thyroid carcinoma, cholangiocarcinoma, Ewing sarcoma, liver and breast cancer were [...]

Language: Английский

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