{"doi":"10.1021/acs.biochem.6b00629","title":"Chemoproteomic Evaluation of Target Engagement by the Cyclin-Dependent Kinase 4 and 6 Inhibitor Palbociclib Correlates with Cancer Cell Response","abstract":null,"journal":"Biochemistry","year":2016,"id":604956,"datarank":1.5933879296616318,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"self_citation_contribution":0.5333022092234121,"citation_network_contribution":1.0600857204382197,"self_endowment_contribution":0.5333022092234121,"citer_contribution":1.0600857204382197,"corpus_percentile":null,"corpus_rank":null,"citation_count":34,"citer_count":31,"citers_with_citation_signal":27,"citers_with_endowment":27,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":50458,"name":"Geeta Sharma","orcid":null,"position":1,"is_corresponding":false},{"id":1552296,"name":"Heidi Brown","orcid":null,"position":2,"is_corresponding":false},{"id":1552297,"name":"Jiangyue Wu","orcid":null,"position":3,"is_corresponding":false},{"id":1552298,"name":"Arwin Aban","orcid":null,"position":4,"is_corresponding":false},{"id":1552299,"name":"Subha Vogeti","orcid":null,"position":5,"is_corresponding":false},{"id":1552301,"name":"Senait Alemayehu","orcid":null,"position":6,"is_corresponding":false},{"id":1552302,"name":"Maria Sykes","orcid":null,"position":7,"is_corresponding":false},{"id":1552303,"name":"Jonathan S. Rosenblum","orcid":null,"position":8,"is_corresponding":false},{"id":1552304,"name":"John W. Kozarich","orcid":null,"position":9,"is_corresponding":false},{"id":1552295,"name":"Tyzoon K. Nomanbhoy","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Chemoproteomic Evaluation of Target Engagement by the Cyclin-Dependent Kinase 4 and 6 Inhibitor Palbociclib Correlates with Cancer Cell Response","abstract":"Palbociclib is a cyclin-dependent kinase (CDK) 4/CDK6 inhibitor approved for breast cancer that is estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative. We profiled palbociclib in cells either sensitive or resistant to the drug using an ATP/ADP probe-based chemoproteomics platform. Palbociclib only engaged CDK4 or CDK6 in sensitive cells. In resistant cells, no inhibition of CDK4 or CDK6 was observed, although the off-target profiles were similar in both cell types. Prolonged incubation of sensitive cells with the compound (24 h) resulted in the downregulation of additional kinases, including kinases critical for cell cycle progression. This downregulation is consistent with cell cycle arrest caused by palbociclib treatment. Both the direct and indirect targets were also observed in a human tumor xenograft study using the COLO-205 cell line in which phosphorylation of the retinoblastoma protein was tracked as the pharmacodyanamic marker. Together, these results suggest that this probe-based approach could be an important strategy toward predicting patient responsiveness to palbociclib.","is_dataset_classified":null,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"27571378","pmcid":null,"openalex_id":"https://openalex.org/W2520173420","authors":[],"funders":[{"funder_name":"Kyorin pharmaceuticals","grant_id":"","title":null}],"total_grants":1,"fwci":2.5391,"citation_percentile":0.89889937,"influential_citations":0,"citation_trend":[{"year":2017,"count":2},{"year":2018,"count":3},{"year":2019,"count":5},{"year":2020,"count":8},{"year":2021,"count":3},{"year":2022,"count":6},{"year":2023,"count":5},{"year":2024,"count":1},{"year":2026,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://pubs.acs.org/doi/pdf/10.1021/acs.biochem.6b00629","host_type":"publisher"},{"url":"https://doi.org/10.1021/acs.biochem.6b00629","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/27571378","host_type":"repository"}],"fields_of_study":["Advanced Breast Cancer Therapies","Cancer-related Molecular Pathways","Chronic Lymphocytic Leukemia Research"],"mesh_terms":["Animals","Humans","Neoplasms","Piperazines","Pyridines","Xenograft Model Antitumor Assays","Proteomics","Cell Line, Tumor","Protein Kinase Inhibitors","Cyclin-Dependent Kinase 4","Cyclin-Dependent Kinase 6","Mice"],"keywords":["Palbociclib","Cyclin-dependent kinase 6","Cyclin-dependent kinase","Kinase","Cyclin-dependent kinase 4","Cancer research","Downregulation and upregulation","Cell cycle","CDK inhibitor","Chemistry","Cancer","Cell biology","Cyclin-dependent kinase 2","Biology","Cell","Breast cancer","Protein kinase A","Biochemistry","Metastatic breast cancer","Genetics"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T01:16:10.994443Z","pmid":null,"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":[]}