{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Milano SK"],"funding":["Science and Engineering Research Board","Canterbury Medical Research Foundation","NCI NIH HHS","NIH","NIGMS NIH HHS"],"pagination":["101535"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8784640"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["298(2)"],"pubmed_abstract":["Cancer cells frequently exhibit uncoupling of the glycolytic pathway from the TCA cycle (i.e., the \"Warburg effect\") and as a result, often become dependent on their ability to increase glutamine catabolism. The mitochondrial enzyme Glutaminase C (GAC) helps to satisfy this 'glutamine addiction' of cancer cells by catalyzing the hydrolysis of glutamine to glutamate, which is then converted to the TCA-cycle intermediate α-ketoglutarate. This makes GAC an intriguing drug target and spurred the molecules derived from bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (the so-called BPTES class of allosteric GAC inhibitors), including CB-839, which is currently in clinical trials. However, none of the drugs targeting GAC are yet approved for cancer treatment and their mechanism of ac"],"journal":["The Journal of biological chemistry"],"pubmed_title":["New insights into the molecular mechanisms of glutaminase C inhibitors in cancer cells using serial room temperature crystallography."],"pmcid":["PMC8784640"],"funding_grant_id":["GM122575","R35 GM122575","EMR/2016-002141","P30GM126166","R01 CA201402"],"pubmed_authors":["Ramachandran S","Finke A","McDermott LA","Sukumar N","Kriksunov I","Huang Q","Schuller DJ","Szebenyi DM","Cerione RA","Nguyen TT","Katt WP","Milano SK","Arenholz E"],"additional_accession":[]},"is_claimable":false,"name":"New insights into the molecular mechanisms of glutaminase C inhibitors in cancer cells using serial room temperature crystallography.","description":"Cancer cells frequently exhibit uncoupling of the glycolytic pathway from the TCA cycle (i.e., the \"Warburg effect\") and as a result, often become dependent on their ability to increase glutamine catabolism. The mitochondrial enzyme Glutaminase C (GAC) helps to satisfy this 'glutamine addiction' of cancer cells by catalyzing the hydrolysis of glutamine to glutamate, which is then converted to the TCA-cycle intermediate α-ketoglutarate. This makes GAC an intriguing drug target and spurred the molecules derived from bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (the so-called BPTES class of allosteric GAC inhibitors), including CB-839, which is currently in clinical trials. However, none of the drugs targeting GAC are yet approved for cancer treatment and their mechanism of ac","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Feb","modification":"2026-05-09T02:27:57.514Z","creation":"2022-02-11T15:40:58.442Z"},"accession":"S-EPMC8784640","cross_references":{"pubmed":["34954143"],"doi":["10.1016/j.jbc.2021.101535"]}}