9GQL

Human MTH1 in complex with stanozolol

This is a non-PDB format compatible entry.

Summary for 9GQL

• Entry DOI: 10.2210/pdb9gql/pdb
• Descriptor: Oxidized purine nucleoside triphosphate hydrolase, stanozolol, GLYCEROL, ... (5 entities in total)
• Functional Keywords: mth1, stanozolol, steroid, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 18488.11

Authors

Scaletti Hutchinson, E.,Gustafsson Westergren, R.,Stenmark, P. (deposition date: 2024-09-09, release date: 2025-08-13, Last modification date: 2025-09-10)

Primary citation

Scaletti Hutchinson, E.,Gustafsson Westergren, R.,Almlof, I.,Jemth, A.S.,Scobie, M.,Warpman Berglund, U.,Helleday, T.,Stenmark, P.
The anabolic steroid stanozolol is a potent inhibitor of human MutT homolog 1.
Febs Lett., 2025

PubMed Abstract: 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.

PubMed: 40878820
DOI: 10.1002/1873-3468.70116

Experimental method

X-RAY DIFFRACTION (1.401 Å)