| Literature DB >> 29660984 |
Chelsea E Powell1, Yang Gao2, Li Tan1, Katherine A Donovan1, Radosław P Nowak1, Amanda Loehr2, Magda Bahcall, Eric S Fischer1, Pasi A Jänne, Rani E George2, Nathanael S Gray1.
Abstract
We present the development of the first small molecule degraders that can induce anaplastic lymphoma kinase (ALK) degradation, including in non-small-cell lung cancer (NSCLC), anaplastic large-cell lymphoma (ALCL), and neuroblastoma (NB) cell lines. These degraders were developed through conjugation of known pyrimidine-based ALK inhibitors, TAE684 or LDK378, and the cereblon ligand pomalidomide. We demonstrate that in some cell types degrader potency is compromised by expression of drug transporter ABCB1. In addition, proteomic profiling demonstrated that these compounds also promote the degradation of additional kinases including PTK2 (FAK), Aurora A, FER, and RPS6KA1 (RSK1).Entities:
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Year: 2018 PMID： 29660984 PMCID： PMC6294449 DOI： 10.1021/acs.jmedchem.7b01655
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446