{"doi":"10.1039/d2sc05749b","title":"Stimulation of natural killer cells with small molecule inhibitors of CD38 for the treatment of neuroblastoma","abstract":"values. We have begun to explore structure activity relationships for CD38 inhibition through derivatization of our most effective hit molecule to develop a new compound with lead-like physicochemical properties and improved potency. We have demonstrated that our derivatized inhibitor, compound 2, elicits immunomodulatory effects in NK cells by increasing cell viability by 190 ± 36% in multiple donors and by significantly increasing interferon gamma. Additionally, we have illustrated that NK cells exhibited enhanced cytotoxicity toward NB cells (14% reduction of NB cells over 90 minutes) when given a combination treatment of our inhibitor and the immunocytokine ch14.18-IL2. Herein we describe the synthesis and biological evaluation of small molecule CD38 inhibitors and demonstrate their potential utility as a novel approach to NB immunotherapy. These compounds represent the first examples of small molecules that stimulate immune function for the treatment of cancer.","journal":"Chemical Science","year":2023,"id":372105,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"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":880133,"name":"Thomas Z. Benton","orcid":"0000-0002-1353-8374","position":1,"is_corresponding":false},{"id":1132528,"name":"Ivett Piña","orcid":"0000-0002-3417-4418","position":2,"is_corresponding":false},{"id":994013,"name":"Megan J. Francis","orcid":null,"position":3,"is_corresponding":false},{"id":422505,"name":"Leticia Reyes","orcid":"0000-0001-5967-5860","position":4,"is_corresponding":false},{"id":491663,"name":"Nathan G. Dolloff","orcid":"0000-0002-9181-2180","position":5,"is_corresponding":false},{"id":601083,"name":"Yuri K. Peterson","orcid":"0000-0002-4005-9678","position":6,"is_corresponding":false},{"id":852867,"name":"Patrick M. Woster","orcid":"0000-0002-9471-1916","position":7,"is_corresponding":false},{"id":880132,"name":"Catherine M. Mills","orcid":"0000-0002-1423-6327","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T01:15:54.000926Z","pmid":"36845935","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":[]}