WZ-3146 acts as a novel small molecule inhibitor of KIF4A to inhibit glioma progression by inducing apoptosis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38937742", "kind": "science-record", "revision": 4, "content_hash": "sha256:4c2ac7eb1d55482d75f8a904e43f884ba3a3a96963cfd5bf69c9e3ff084e33cb", "created_at": "2026-11-01T20:29:00Z", "updated_at": "2026-11-01T22:54:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "WZ-3146 acts as a novel small molecule inhibitor of KIF4A to inhibit glioma progression by inducing apoptosis.", "doi": "10.1186/s12935-024-03409-y", "pmid": "38937742", "authors": ["Tao Yan", "Qing Jiang", "Guangpu Ni", "Haofeng Ma", "Yun Meng", "Guiqiong Kang", "Meifang Xu", "Fei Peng", "Huadong Li", "Xin Chen", "Mingguang Wang"], "journal": "Cancer cell international", "year": 2024, "abstract": "BACKGROUND: Glioma is considered the most common primary malignant tumor of the central nervous system. Although traditional treatments have not achieved satisfactory outcomes, recently, targeted therapies for glioma have shown promising efficacy. However, due to the single-target nature of targeted therapy, traditional targeted therapies are ineffective; thus, novel therapeutic targets are urgently needed.\nMETHODS: The gene expression data for glioma patients were derived from the GEO (GSE4290, GSE50161), TCGA and CGGA databases. Next, the upregulated genes obtained from the above databases were cross-analyzed, finally, 10 overlapping genes (BIRC5, FOXM1, EZH2, CDK1, KIF11, KIF4A, NDC80, PBK, RRM2, and TOP2A) were ultimately screened and only KIF4A expression has the strongest correlation with clinical characteristics in glioma patients. Futher, the TCGA and CGGA database were utilized to explore the correlation of KIF4A expression with glioma prognosis. Then, qRT-PCR and Western blot was used to detect the KIF4A mRNA and protein expression level in glioma cells, respectively. And WZ-3146, the small molecule inhibitor targeting KIF4A, were screened by Cmap analysis. Subsequently, the effect of KIF4A knockdown or WZ-3146 treatment on glioma was measured by the MTT, EdU, Colony formation assay and Transwell assay. Ultimately, GSEA enrichment analysis was performed to find that the apoptotic pathway could be regulated by KIF4A in glioma, in addition, the effect of WZ-3146 on glioma apoptosis was detected by flow cytometry and Western blot.\nRESULTS: In the present study, we confirmed that KIF4A is abnormally overexpressed in glioma. In addition, KIF4A overexpression is a key indicator of glioma prognosis; moreover, suppressing KIF4A expression can inhibit glioma progression. We also discovered that WZ-3146, a small molecule inhibitor of KIF4A, can induce apoptosis in glioma cells and exhibit antiglioma effects.\nCONCLUSION: In conclusion, these observations demonstrated that targeting KIF4A can inhibit glioma progression. With further research, WZ-3146, a small molecule inhibitor of KIF4A, could be combined with other molecular targeted drugs to cooperatively inhibit glioma progression.", "claims": [{"id": "claim-method", "statement": "Kaplan‒Meier survival analysis demonstrated that glioma patients with high KIF4A expression had shorter survival times than patients with low KIF4A expression. Next, univariate and multivariate Cox regression analysis were carried out to confirm the feasibility of KIF4A as an independent prognostic factor for glioma (Fig. 2A). Furthermore, ROC curves were generated to assess the clinical diagnostic value of KIF4A for glioma in the TCGA and CGGA databases.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38937742", "locator": "sections[16] \"KIF4A over-expression was associated with glioma prognosis and could be an independent prognostic factor for glioma\" paragraph 2", "quote": "Kaplan‒Meier survival analysis demonstrated that glioma patients with high KIF4A expression had shorter survival times than patients with low KIF4A expression."}, {"asset": "source:pmid:38937742", "locator": "sections[16] \"KIF4A over-expression was associated with glioma prognosis and could be an independent prognostic factor for glioma\" paragraph 2", "quote": "Next, univariate and multivariate Cox regression analysis were carried out to confirm the feasibility of KIF4A as an independent prognostic factor for glioma (Fig."}, {"asset": "source:pmid:38937742", "locator": "sections[16] \"KIF4A over-expression was associated with glioma prognosis and could be an independent prognostic factor for glioma\" paragraph 2", "quote": "2A)."}, {"asset": "source:pmid:38937742", "locator": "sections[16] \"KIF4A over-expression was associated with glioma prognosis and could be an independent prognostic factor for glioma\" paragraph 2", "quote": "Furthermore, ROC curves were generated to assess the clinical diagnostic value of KIF4A for glioma in the TCGA and CGGA databases."}], "state": "complete"}, {"id": "claim-data-access", "statement": "No datasets were generated or analysed during the current study.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38937742", "locator": "sections[27] \"notes\" paragraph 1", "quote": "No datasets were generated or analysed during the current study."}], "state": "complete"}, {"id": "claim-target-result", "statement": "KIF4A upregulation is associated with poor glioma prognosis and is an independent prognostic risk factor.", "kind": "quantitative", "target": {"value": 0.001, "unit": "p-value", "tolerance": null, "source": "Univariate Cox regression analysis indicated that KIF4A expression was negatively related to glioma prognosis in the TCGA database (HR = 1.870, P < 0.001), and similar results were obtained in the CGGA database (HR = 1.777, P < 0.001) (Fig. 2B)."}, "evidence": [{"asset": "source:pmid:38937742", "locator": "sections[16] \"KIF4A over-expression was associated with glioma prognosis and could be an independent prognostic factor for glioma\" paragraph 2", "quote": "Univariate Cox regression analysis indicated that KIF4A expression was negatively related to glioma prognosis in the TCGA database (HR = 1.870, P < 0.001), and similar results were obtained in the CGGA database (HR = 1.777, P < 0.001) (Fig. 2B)."}, {"asset": "source:pmid:38937742", "locator": "sections[16] \"KIF4A over-expression was associated with glioma prognosis and could be an independent prognostic factor for glioma\" paragraph 2", "quote": "Overall, these results supported the idea that high KIF4A expression is an independent factor indicating poor prognosis in glioma."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "KIF4A upregulation is associated with poor glioma prognosis and is an independent prognostic risk factor.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:38937742"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Then, qRT-PCR and Western blot was used to detect the KIF4A mRNA and protei", "apoptosis was detected by flow cytometry and Western blot. RESULTS: In the present study, we confirmed"], "order_basis": "paper_text_order:1054", "id": "assay:2"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["analysis. Subsequently, the effect of KIF4A knockdown or WZ-3146 treatment on glioma was measured"], "order_basis": "paper_text_order:1287", "id": "assay:3"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["WZ-3146 on glioma apoptosis was detected by flow cytometry and Western blot. RESULTS: In the present st"], "order_basis": "paper_text_order:1598", "id": "assay:4"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["atory of Linyi People’s Hospital. The glioma cell lines were cultured in Dulbecco’s modified Eagle’s medium (DMEM;", "10% FBS and 1% dual antibiotic solution. All cell lines were cultured at 37 °C and 5% CO2 in a cell culture incuba", "eople’s Hospital. The glioma cell lines were cultured in Dulbecco’s modified Eagle’s medium (DMEM; C1", "um (FBS; 10270-106, Gibco, USA). HUVECs were cultured in Roswell Park Memorial Institute 1640 (RPMI-1"], "order_basis": "paper_text_order:2465", "id": "assay:5"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Kaplan‒Meier survival analysis demonstrated that glioma patients with high KIF4A expression had shorter survival times than patients with low KIF4A expression. Next, univariate and multivariate Cox regression analysis were carried out to confirm the feasibility of KIF4A as an independent prognostic factor for glioma (Fig. 2A). Furthermore, ROC curves were generated to assess the clinical diagnostic value of KIF4A for glioma in the TCGA and CGGA databases."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}