Unknown

Dataset Information

0

N-quinoline-benzenesulfonamide derivatives exert potent anti-lymphoma effect by targeting NF-κB.


ABSTRACT: We previously identified the N-quinoline-benzenesulfonamide (NQBS) scaffold as a potent inhibitor of nuclear factor-κB (NF-κB) translocation. Now, we report the structure-activity relationship of compounds with the NQBS scaffold in models of diffuse large B-cell lymphoma (DLBCL). We identified CU-O42, CU-O47, and CU-O75 as NQBS analogs with the most potent cytotoxic activity in DLBCL lines. Their anti-lymphoma effect was mediated by NF-κB sequestration to the cytoplasm of DLBCL cells. Internal Coordinates Mechanics analysis suggested direct binding between CU-O75 and IκBα/p50/p65 which leads to the stabilization of the NF-κB trimer. A whole cellular thermal shift assay confirmed direct binding of the NQBS to IκBα, an inhibitory component of the IκBα/p50/p65 trimer. Lymphoma cell line sequencing revealed CU-O75 induced downregulation of NF-κB-dependent genes and DeMAND analysis identified IκBα as one of the top protein targets for CU-O75. CU-O42 was potent in inhibiting tumor growth in two mouse models of aggressive lymphomas.

SUBMITTER: Kalac M 

PROVIDER: S-EPMC7744703 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

2020-11-18 | GSE161677 | GEO
| PRJNA679056 | ENA
| S-EPMC4018120 | biostudies-literature
| S-EPMC6084461 | biostudies-literature
| S-EPMC6152673 | biostudies-literature
| S-EPMC8588554 | biostudies-literature
| S-EPMC10272839 | biostudies-literature
| S-EPMC6152030 | biostudies-literature
| S-EPMC7225962 | biostudies-literature
| S-EPMC8234599 | biostudies-literature