WRN-IN-26 

WRN-IN-26 is an orally active Werner syndrome helicase (WRN) inhibitor with a human K_i value of 58.7 μM and an IC₅₀ value of 0.026 μM. WRN-IN-26 selectively targets the cysteine residues of WRN. WRN-IN-26 induces the expression of p21 protein in MSI-H tumor cells. WRN-IN-26 inhibits the growth of MSI-H tumor cells and exhibits potent in vivo efficacy in MSI-H xenograft tumor models. WRN-IN-26 can be used for the research of microsatellite instability-high (MSI-H) cancers^[1].

WRN-IN-26 (compound 26) inhibits WRN helicase DNA unwinding activity with an IC₅₀ of 0.026 μM^[1].
WRN-IN-26 inhibits wild-type WRN helicase ATPase activity with an IC₅₀ of 0.023 μM^[1].
WRN-IN-26 irreversibly inhibits WRN helicase with an inactivation rate constant (k_inact/K_i) of 459 M^-1s^-1[1].
WRN-IN-26 induces p21 protein expression in HCT116 MSI-H colorectal tumor cells with an EC₅₀ of 1.8 μM^[1].
WRN-IN-26 inhibits viability of HCT116 MSI-H colorectal tumor cells with an IC50 of 0.674 μM, while showing no inhibition of viability in SW620 MSS colorectal tumor cells up to 50 μM, demonstrating synthetic lethality for MSI-H cells^[1].
WRN-IN-26 (2 μM; 2 hours) exclusively engages WRN at residue C727 in HCT116 MSI-H colorectal tumor cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

WRN-IN-26 (compound 26) (300 mg/kg; p.o.; twice daily; 1 or 2 days) induces p21 protein expression in HCT116 MSI-H xenograft tumors, reaching a 4.2-fold increase after 2 days of treatment, demonstrating significant WRN inhibition in vivo^[1].
WRN-IN-26 (300 mg/kg; p.o.; twice daily; 21 days) achieves 90% tumor growth inhibition in HCT116 MSI-H xenograft tumors with good tolerability^[1].
WRN-IN-26 (300 mg/kg; p.o.; twice daily; 18 days) does not inhibit tumor growth in SW620 MSS xenograft tumors, demonstrating synthetic lethality specific to MSI-H tumors in vivo^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

560.58

C₂₈H₂₇F₃N₂O₅S

3059172-54-9

O=C(N([C@H]1CS(=O)(C=C1)=O)CC2=CC=NC(C(C)(O)C)=C2)[C@@H](C3=CC=C(C4=CC=C(F)C(F)=C4)C=C3F)OC

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Caravella JA, et al. Design of Cyclic Vinyl Sulfones as WRN Covalent Inhibitors from Noncovalent Binders. J Med Chem. Published online April 29, 2026.