{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Mosher EP"],"funding":["NIA NIH HHS","NIAID NIH HHS","NIGMS NIH HHS"],"pagination":["588-596"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8626780"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["100(6)"],"pubmed_abstract":["Tenofovir (TFV) is a key component of human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP). TFV is a nucleotide analog reverse-transcriptase inhibitor prodrug that requires two separate phosphorylation reactions by intracellular kinases to form the active metabolite tenofovir-diphosphate (TFV-DP). Muscle-type creatine kinase (CKM) has previously been demonstrated to be the kinase most responsible for the phosphorylation of tenofovir-monophosphate (TFV-MP) to the active metabolite in colon tissue. Because of the importance of CKM in TFV activation, genetic variation in CKM may contribute to interindividual variability in TFV-DP levels. In the present study, we report 10 naturally occurring CKM mutations that reduced TFV-MP phosphorylation in vitro: T35I, R43Q, I92M, H97Y, R130"],"journal":["Molecular pharmacology"],"pubmed_title":["Naturally Occurring Mutations to Muscle-Type Creatine Kinase Impact Its Canonical and Pharmacological Activities in a Substrate-Dependent Manner In Vitro."],"pmcid":["PMC8626780"],"funding_grant_id":["R01 AG064908","T32 GM008763","R01 AI128781"],"pubmed_authors":["Eberhard CD","Bumpus NN","Mosher EP"],"additional_accession":[]},"is_claimable":false,"name":"Naturally Occurring Mutations to Muscle-Type Creatine Kinase Impact Its Canonical and Pharmacological Activities in a Substrate-Dependent Manner In Vitro.","description":"Tenofovir (TFV) is a key component of human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP). TFV is a nucleotide analog reverse-transcriptase inhibitor prodrug that requires two separate phosphorylation reactions by intracellular kinases to form the active metabolite tenofovir-diphosphate (TFV-DP). Muscle-type creatine kinase (CKM) has previously been demonstrated to be the kinase most responsible for the phosphorylation of tenofovir-monophosphate (TFV-MP) to the active metabolite in colon tissue. Because of the importance of CKM in TFV activation, genetic variation in CKM may contribute to interindividual variability in TFV-DP levels. In the present study, we report 10 naturally occurring CKM mutations that reduced TFV-MP phosphorylation in vitro: T35I, R43Q, I92M, H97Y, R130","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Dec","modification":"2025-04-26T05:24:22.076Z","creation":"2022-02-11T13:34:41.773Z"},"accession":"S-EPMC8626780","cross_references":{"pubmed":["34561299"],"doi":["10.1124/molpharm.121.000348"]}}