{"doi":"10.1039/d3sc04541b","title":"Discovery of a selective TC-PTP degrader for cancer immunotherapy","abstract":"s and >110-fold selectivity over the closely related PTP1B. TP1L elevates the phosphorylation level of TC-PTP substrates including pSTAT1 and pJAK1, while pJAK2, the substrate of PTP1B, is unaffected by the TC-PTP degrader. TP1L also intensifies interferon gamma (IFN-γ) signaling and increases MHC-I expression. In Jurkat cells, TP1L activates TCR signaling through increased phosphorylation of LCK. Furthermore, in a CAR-T cell and KB tumor cell co-culture model, TP1L enhances CAR-T cell mediated tumor killing efficacy through activation of the CAR-T cells. Thus, we surmise that TP1L not only provides a unique opportunity for in-depth interrogation of TC-PTP biology but also serves as an excellent starting point for the development of novel immunotherapeutic agents targeting TC-PTP.","journal":"Chemical Science","year":2023,"id":338923,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"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":662145,"name":"Jiajun Dong","orcid":"0000-0002-6901-5070","position":1,"is_corresponding":false},{"id":1071942,"name":"Yiming Miao","orcid":"0000-0001-6422-1118","position":2,"is_corresponding":false},{"id":662146,"name":"Yunpeng Bai","orcid":"0000-0002-5879-3555","position":3,"is_corresponding":false},{"id":1021288,"name":"Zihan Qu","orcid":"0009-0004-8446-8459","position":4,"is_corresponding":false},{"id":894561,"name":"Brenson A. Jassim","orcid":null,"position":5,"is_corresponding":false},{"id":300810,"name":"Bo Huang","orcid":"0000-0001-6196-5373","position":6,"is_corresponding":false},{"id":1028110,"name":"Quyen Nguyen","orcid":"0009-0001-7232-8932","position":7,"is_corresponding":false},{"id":294279,"name":"Yuan Ma","orcid":"0000-0002-3741-3277","position":8,"is_corresponding":false},{"id":1071943,"name":"Allison A. Murray","orcid":"0000-0002-1586-2813","position":9,"is_corresponding":false},{"id":591953,"name":"Jinyue Li","orcid":"0000-0003-2979-1734","position":10,"is_corresponding":false},{"id":308182,"name":"Philip S. Low","orcid":"0000-0001-9042-5528","position":11,"is_corresponding":false},{"id":341920,"name":"Zhong-Yin Zhang","orcid":"0000-0001-5527-7910","position":12,"is_corresponding":false},{"id":680169,"name":"Jinmin Miao","orcid":"0000-0001-7471-0847","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T01:10:40.496978Z","pmid":"38020389","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":[]}