Identification of a Selective Inhibitor of Human NFS1, a Cysteine Desulfurase Involved in Fe-S Cluster Assembly, via Structure-Based Virtual Screening.

ABSTRACT: Human cysteine desulfurase (NFS1) participates in numerous critical cellular processes, including iron-sulfur (Fe-S) cluster biosynthesis and tRNA thiolation. NFS1 overexpression has been observed in a variety of cancers, and thus it has been considered a promising anti-tumor therapeutic target. To date, however, no inhibitors targeting NFS1 have been identified. Here, we report the identification of the first potent small-molecule inhibitor (Compound 53, PubChem CID 136847320) of NFS1 through a combination of virtual screening and biological validation. Compound 53 exhibited good selectivity against two other pyridoxal phosphate (PLP)-dependent enzymes. Treatment with Compound 53 inhibited the proliferation of lung cancer (A549) cells (IC₅₀ = 16.3 ± 1.92 μM

SUBMITTER: Zhu Z 

PROVIDER: S-EPMC11942905 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature