A Mitochondria-Targeting SIRT3 Inhibitor with Activity against Diffuse Large B Cell Lymphoma.

ABSTRACT: Diffuse large B-cell lymphomas (DLBCLs) are heterogeneous cancers that still require better and less toxic treatments. SIRT3, a member of the sirtuin family of NAD⁺-dependent protein deacylase, is critical for DLBCL growth and survival. A mitochondria-targeted SIRT3 small-molecule inhibitor, YC8-02, exhibits promising activity against DLBCL. However, YC8-02 has several limitations including poor solubility. Here, we report our medicinal chemistry efforts that led to an improved mitochondria-targeted SIRT3 inhibitor, SJ-106C, achieved by using a triethylammonium group, which helps to increase both solubility and SIRT3 inhibition potency. SJ-106C, while still inhibiting SIRT1 and SIRT2, is enriched in the mitochondria to help with SIRT3 inhibition. It is more active against DLBCL

SUBMITTER: Jana S 

PROVIDER: S-EPMC11403614 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature