GSK4418959 (IDE275) is a selective small-molecule inhibitor of Werner syndrome helicase (WRN), a RecQ family DNA helicase critical for maintaining genome stability, especially in microsatellite instability-high (MSI-H) tumors. WRN dependency is a synthetic lethal vulnerability in MSI-H cancers, and GSK4418959 exploits this by targeting WRN ATPase activity. In biochemical assays, GSK4418959 inhibits WRN with IC₅₀ values in the low nanomolar range (~10–50 nM). In MSI-H cancer cell lines, it exhibits potent antiproliferative activity (e.g., GI₅₀ values <100 nM) while sparing microsatellite-stable (MSS) cells, confirming selectivity. In vivo, GSK4418959 shows tumor growth inhibition in MSI-H xenograft models without significant toxicity. These findings support its development as a targeted therapy for MSI-H tumors, particularly colorectal and endometrial cancers.
MedKoo Cat#: 128834
Name: GSK4418959
CAS#: 3064599-36-3
Chemical Formula: C31H30F4N4O5S
Exact Mass: 646.1873
Molecular Weight: 646.66
Elemental Analysis: C, 57.58; H, 4.68; F, 11.75; N, 8.66; O, 12.37; S, 4.96
The following data is based on the product molecular weight 646.66 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
