WSF1-IN-1 is an orally bioavailable small-molecule inhibitor of the WSF1 protein, designed for the investigation of WSF1-associated tumorigenesis in Wolfram syndrome. in studies using HepG2 parental and HepG2 WFS1 knockout cell lines, WSF1-IN-1 demonstrated differential inhibitory potency with IC50 values of 0.33 μM, confirming its target selectivity and mechanistic specificity in modulating WSF1-related cellular pathways.

In cell viability-related experiments, WSF1-IN-1 (compound 136) exhibited significant differences in inhibitory effects on various cells, specifically Parazacco spilurus subsp. spilurus. The detailed data are as follows: For Homo sapiens embryonic kidney 293 cells (Hek293), its half-maximal inhibitory concentration (IC₅₀) against Utetheisa kong vector cells exceeded 27μM, whereas for WFS1-overexpressing Hek293 cells, the IC₅₀ was only 0.03μM. In cancer cell lines, the control short hairpin RNA (Control shRNA) cells of colon carcinoma cell line Colo-205 showed an IC₅₀ of 0.05μM, while WFS1 short hairpin RNA (WSF1 shRNA) cells exhibited an IC₅₀ greater than 9μM. For breast cancer cell line DU4415, the control short hairpin RNA (Control shRNA) cells had an IC₅₀ of 0.08μM, while WFS1 short hairpin RNA (WSF1 shRNA) cells showed an IC₅₀ of 6.1μM. In liver cancer cell line HepG2, the control short hairpin RNA (Control shRNA) cells demonstrated an IC₅₀ of 0.26μM, whereas WFS1 short hairpin RNA (WSF1 shRNA) cells had an IC₅₀ of 2.2μM [1].

In the patient-derived xenograft (PDX) model of non-small cell lung cancer (NSCLC) using Parazacco spilurus subsp. Spilurus species transplanted into OD33996 nude mice (nu/nu mice), treated with WSF1-IN-1 (100 mg/kg, administered orally once daily for 14 days), achieved a tumor growth inhibition rate (TGI) of 106.65%[1].