{"doi":"10.1021/acsptsci.2c00241","title":"Novel, Brain-Permeable, Cross-Species Benzothiazole Inhibitors of Microsomal Prostaglandin E Synthase-1 (mPGES-1) Dampen Neuroinflammation <i>In Vitro</i> and <i>In Vivo</i>","abstract":"Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible enzyme of the cyclooxygenase (COX) cascade that generates prostaglandin E2 (PGE 2 ) during inflammatory conditions. PGE 2 is known to be a potent immune signaling molecule that mediates both peripheral and central inflammations. Inhibition of mPGES-1, rather than COX, may overcome the cardiovascular side effects associated with long-term COX inhibition by providing a more specific strategy to target inflammation. However, mPGES-1 inhibitor development is hampered by the large differences in cross-species activity due to the structural differences between the human and murine mPGES-1. Here, we report that our thiazole-based mPGES-1 inhibitors, compounds 11 ( UT-11 ) and 19 derived from two novel scaffolds, were able to suppress PGE 2 production in human (SK-N-AS) and murine (BV2) cells. The IC 50 values of inhibiting PGE 2 production in human and murine cells were 0.10 and 2.00 μM for UT-11 and 0.43 and 1.55 μM for compound 19, respectively. Based on in vitro and in vivo pharmacokinetic data, we selected UT-11 for evaluation in a lipopolysaccharide (LPS)-induced inflammation model. We found that our compound significantly suppressed proinflammatory cytokines and chemokines in the hippocampus but not in the kidney. Taken together, we demonstrated the potential of UT-11 in treating neuroinflammatory conditions, including epilepsy and stroke, and warrant further optimization.","journal":"ACS Pharmacology & Translational Science","year":2023,"id":352414,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1098307,"name":"Rajib Bhuniya","orcid":null,"position":1,"is_corresponding":false},{"id":986385,"name":"Xinrui Yuan","orcid":"0009-0006-2032-0126","position":2,"is_corresponding":false},{"id":1097919,"name":"Andhavaram Ramaraju","orcid":"0000-0001-6708-1691","position":3,"is_corresponding":false},{"id":320403,"name":"Yu Chen","orcid":"0000-0003-1348-8992","position":4,"is_corresponding":false},{"id":336725,"name":"Ying Yu","orcid":"0000-0002-6476-1752","position":5,"is_corresponding":false},{"id":696625,"name":"Keyur Parmar","orcid":"0000-0003-4127-4115","position":6,"is_corresponding":false},{"id":705718,"name":"Zaid H. Temrikar","orcid":null,"position":7,"is_corresponding":false},{"id":966694,"name":"Ashish Srivastava","orcid":"0000-0002-7785-6718","position":8,"is_corresponding":false},{"id":696626,"name":"Bernd Meibohm","orcid":"0000-0003-3923-3648","position":9,"is_corresponding":false},{"id":336726,"name":"Jianxiong Jiang","orcid":"0000-0003-3955-8928","position":10,"is_corresponding":false},{"id":827645,"name":"Chao‐Yie Yang","orcid":"0000-0002-5445-0109","position":11,"is_corresponding":false},{"id":338275,"name":"Madison N. Sluter","orcid":null,"position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:12:50.107998Z","pmid":"37082746","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}