2025/07/27 by Emma Scaletti Hutchinson, Robert Gustafsson Westergren, Ingrid Almlöf +5 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Estrogen and related hormone effects #RNA and protein synthesis mechanisms #Steroid Chemistry and Biochemistry
paper · doi:10.1002/1873-3468.70116
openalex publication_date 2025/07/27 · openalex created_date 2025/07/28 · openalex updated_date 2026/08/01
Human MutT homolog 1 (hMTH1) removes damaged nucleotides from the nucleotide pool, preventing their incorporation into DNA. Due to its potential as an anticancer drug target, hMTH1 has been the focus of several inhibitor development studies. Unexpectedly, we show that the anabolic steroid stanozolol (Stz) is a potent nanomolar inhibitor of hMTH1. We present the structure of hMTH1 in complex with Stz, which indicates a unique core scaffold that could be exploited for future inhibitor development. Comparison with human protein structures bound with dihydrotestosterone (DHT) shows hMTH1 is entirely unrelated in terms of its structure. As these DHT binding proteins are all involved in steroid regulation, this makes the identification of Stz as a potent hMTH1 inhibitor all the more unusual.