{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Li S"],"funding":["National Institute of Neurological Disorders and Stroke","NINDS NIH HHS"],"pagination":["764"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9024726"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(4)"],"pubmed_abstract":["Adenosine triphosphate (ATP)-competitive p97 inhibitor CB-5339, the successor of CB-5083, is being evaluated in Phase 1 clinical trials for anti-cancer therapy. Different modes-of-action p97 inhibitors such as allosteric inhibitors are useful to overcome drug-induced resistance, one of the major problems of targeted therapy. We previously demonstrated that allosteric p97 inhibitor NMS-873 can overcome CB-5083-induced resistance in HCT116. Here we employed chemical proteomics and drug-induced thermal proteome changes to identify drug targets, in combination with drug-resistant cell lines to dissect on- and off-target effects. We found that NMS-873 but not CB-5083 affected glycometabolism. By establishing NMS-873-resistant HCT116 cell lines and performing both cell-based and proteomic analys"],"journal":["Pharmaceutics"],"pubmed_title":["NMS-873 Leads to Dysfunctional Glycometabolism in A p97-Independent Manner in HCT116 Colon Cancer Cells."],"pmcid":["PMC9024726"],"funding_grant_id":["R01NS102279","R01NS100815"],"pubmed_authors":["Zhang G","Li S","Wang F","Chou TF"],"additional_accession":[]},"is_claimable":false,"name":"NMS-873 Leads to Dysfunctional Glycometabolism in A p97-Independent Manner in HCT116 Colon Cancer Cells.","description":"Adenosine triphosphate (ATP)-competitive p97 inhibitor CB-5339, the successor of CB-5083, is being evaluated in Phase 1 clinical trials for anti-cancer therapy. Different modes-of-action p97 inhibitors such as allosteric inhibitors are useful to overcome drug-induced resistance, one of the major problems of targeted therapy. We previously demonstrated that allosteric p97 inhibitor NMS-873 can overcome CB-5083-induced resistance in HCT116. Here we employed chemical proteomics and drug-induced thermal proteome changes to identify drug targets, in combination with drug-resistant cell lines to dissect on- and off-target effects. We found that NMS-873 but not CB-5083 affected glycometabolism. By establishing NMS-873-resistant HCT116 cell lines and performing both cell-based and proteomic analys","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2026-05-18T03:14:19.213Z","creation":"2025-04-04T10:02:19.552Z"},"accession":"S-EPMC9024726","cross_references":{"pubmed":["35456598"],"doi":["10.3390/pharmaceutics14040764"]}}