MTHFD Inhibitor Crystal Structures For Acute Myeloid Leukemia

Featuring X-ray crystallography structures of novel MTHFD inhibitors, including a highly selective MTHFD2 inhibitor (compound 31) and a dual MTHFD1/2 inhibitor (compound 34), bound to their targets. The data underpins the discovery of these compounds as potential treatments for acute myeloid leukemia (AML), with structural analysis revealing design principles for isoform selectivity.

Use Cases

• Analyze the cocrystal structure of DS18561882 bound to MTHFD2 to understand the binding site interactions.
• Compare the structural modifications of the aminosulfonamide motif between compounds 31 and 34 to study isoform selectivity determinants.
• Use the PDB files of compounds 31 and 34 for molecular docking studies against MTHFD1 and MTHFD2 targets.
• Validate the hydrogen bond and hydrophobic network reshaping observed in the MTHFD active site from the structural analysis.

Strengths

• Includes solved X-ray crystallography structures of inhibitor-target complexes.
• Provides structural data for two distinct inhibitor types: a selective MTHFD2 inhibitor and a dual MTHFD1/2 inhibitor.
• Data is directly linked to in vitro and in vivo efficacy results, including tumor regression in xenograft models.

Limitations

• The dataset is small in scale, consisting of only 745.8 KB of PDB files, limiting broad statistical analysis.
• No explicit columnar or tabular data is provided, restricting use to structural biology and computational chemistry applications.
• The dataset focuses on a specific chemical scaffold (Tetrahydrochromeno[3,4‑c]pyridin-5-one derivatives), which may limit generalizability.

Provenance

Source

Hao Lin via figshare.

Collection Method

Generated through systematic structure–activity optimization and X-ray crystallography.

Freshness

Last updated in March 2026.