{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhao LM"],"funding":["Fudan University","National Natural Science Foundation of China"],"pagination":["4906-4917"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10692386"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(12)"],"pubmed_abstract":["Following on our recently developed biphenyl-ATDP non-nucleoside reverse transcriptase inhibitor ZLM-66 (SI = 2019.80, <i>S</i> = 1.9 μg/mL), a series of novel heterocycle-substituted ATDP derivatives with significantly improved selectivity and solubility were identified by replacement of the biphenyl moiety of ZLM-66 with heterocyclic group with lower lipophilicity. Evidently, the representative analog <b>7w</b> in this series exhibited dramatically enhanced selectivity and solubility (SI = 12,497.73, <i>S</i> = 4472 μg/mL) in comparison with ZLM-66 (SI = 2019.80, <i>S</i> = 1.9 μg/mL). This new NNRTI conferred low nanomolar inhibition of wild-type HIV-1 strain and tested mutant strains (K103N, L100I, Y181C, E138K, and K103N + Y181C). The analog also demonstrated favorable safety and pharmacokinetic profiles, as evidenced by its insensitivity to CYP and hERG, lack of mortality and pathological damage, and good oral bioavailability in rats (<i>F</i> = 27.1%). Further development of <b>7w</b> for HIV therapy will be facilitated by this valuable information."],"journal":["Acta pharmaceutica Sinica. B"],"pubmed_title":["Structure-based design of novel heterocycle-substituted ATDP analogs as non-nucleoside reverse transcriptase inhibitors with improved selectivity and solubility."],"pmcid":["PMC10692386"],"funding_grant_id":["22077018"],"pubmed_authors":["Wang S","Zhao LM","Clercq E","Chen FE","Pannecouque C"],"additional_accession":[]},"is_claimable":false,"name":"Structure-based design of novel heterocycle-substituted ATDP analogs as non-nucleoside reverse transcriptase inhibitors with improved selectivity and solubility.","description":"Following on our recently developed biphenyl-ATDP non-nucleoside reverse transcriptase inhibitor ZLM-66 (SI = 2019.80, <i>S</i> = 1.9 μg/mL), a series of novel heterocycle-substituted ATDP derivatives with significantly improved selectivity and solubility were identified by replacement of the biphenyl moiety of ZLM-66 with heterocyclic group with lower lipophilicity. Evidently, the representative analog <b>7w</b> in this series exhibited dramatically enhanced selectivity and solubility (SI = 12,497.73, <i>S</i> = 4472 μg/mL) in comparison with ZLM-66 (SI = 2019.80, <i>S</i> = 1.9 μg/mL). This new NNRTI conferred low nanomolar inhibition of wild-type HIV-1 strain and tested mutant strains (K103N, L100I, Y181C, E138K, and K103N + Y181C). The analog also demonstrated favorable safety and pharmacokinetic profiles, as evidenced by its insensitivity to CYP and hERG, lack of mortality and pathological damage, and good oral bioavailability in rats (<i>F</i> = 27.1%). Further development of <b>7w</b> for HIV therapy will be facilitated by this valuable information.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Dec","modification":"2026-05-28T08:57:45.867Z","creation":"2026-05-15T03:07:41.206Z"},"accession":"S-EPMC10692386","cross_references":{"pubmed":["38045058"],"doi":["10.1016/j.apsb.2023.07.008"]}}