{"doi":"10.1021/acsptsci.1c00042","title":"<i>N</i>-Adamantyl Phthalimidine: A New Thalidomide-like Drug That Lacks Cereblon Binding and Mitigates Neuronal and Synaptic Loss, Neuroinflammation, and Behavioral Deficits in Traumatic Brain Injury and LPS Challenge","abstract":"-adamantyl phthalimidine (NAP) as a new thalidomide-like drug to mitigate inflammation without binding to cereblon, a key target associated with the antiproliferative, antiangiogenic, and teratogenic actions seen in this drug class. We utilized a phenotypic drug discovery approach that employed multiple cellular and animal models and ultimately examined immunohistochemical, biochemical, and behavioral measures following controlled cortical impact (CCI) TBI in mice. NAP mitigated LPS-induced inflammation across cellular and rodent models and reduced oligomeric α-synuclein and amyloid-β mediated inflammation. Following CCI TBI, NAP mitigated neuronal and synaptic loss, neuroinflammation, and behavioral deficits, and is unencumbered by cereblon binding, a key protein underpinning the teratogenic and adverse actions of thalidomide-like drugs in humans. In summary, NAP represents a new class of thalidomide-like drugs with anti-inflammatory actions for promising efficacy in the treatment of TBI and potentially longer-term neurodegenerative disorders.","journal":"ACS Pharmacology & Translational Science","year":2021,"id":175282,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":360809,"name":"Weiming Luo","orcid":"0009-0002-3035-3176","position":1,"is_corresponding":false},{"id":305915,"name":"David Tweedie","orcid":"0000-0002-8446-4544","position":2,"is_corresponding":false},{"id":467942,"name":"Dong Seok Kim","orcid":"0000-0001-5637-2469","position":3,"is_corresponding":false},{"id":715809,"name":"Yu Kyung Kim","orcid":"0000-0002-4699-8502","position":4,"is_corresponding":false},{"id":715810,"name":"Inho Hwang","orcid":"0000-0003-2039-3895","position":5,"is_corresponding":false},{"id":716349,"name":"Jung-Eun Gil","orcid":null,"position":6,"is_corresponding":false},{"id":715811,"name":"Baek‐Soo Han","orcid":"0000-0003-3610-7216","position":7,"is_corresponding":false},{"id":715812,"name":"Yung‐Hsiao Chiang","orcid":"0000-0002-8426-4016","position":8,"is_corresponding":false},{"id":716350,"name":"Warren R. Selman","orcid":null,"position":9,"is_corresponding":false},{"id":333743,"name":"Barry J. Hoffer","orcid":"0000-0002-1122-9025","position":10,"is_corresponding":false},{"id":297917,"name":"Nigel H. Greig","orcid":"0000-0002-3032-1468","position":11,"is_corresponding":false},{"id":715808,"name":"Shih‐Chang Hsueh","orcid":"0009-0002-0838-0223","position":0,"is_corresponding":true}],"reference_count":131,"raw_metadata":null,"created_at":"2026-07-18T23:47:11.249697Z","pmid":"33860215","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":[]}