APY0201 / Ajinomoto - LARVOL DELTA

Evaluation of the PIKfyve kinase inhibitor Apilimod against hepatitis E virus infections (EASL-ILC 2024) - "Despite its high risks especially among immunosuppressed patients and pregnant women, the treatment of HEV is limited to the off-label use of nucleoside-analogue ribavirin (RBV) and PEGylated interferon-α... All three tested PIKfyve kinase inhibitors, Apilimod, YM201636 and APY0201 lowered HEV infectivity at nanomolar efficacy in hepatoma cells... Overall, our data suggests that PIKfyve plays a crucial role during the viral entry of HEV. Considering the proven safety profile of Apilimod in previous human clinical trials (unrelated to viral conditions), the pharmacological targeting of PIKfyve kinase activity might guide novel antiviral strategies against HEV infections."

Late-breaking abstract • Ebola Virus Disease • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Infectious Disease • Inflammation • Liver Cancer • Novel Coronavirus Disease • Respiratory Diseases • Solid Tumor

APY0201 Represses Tumor Growth through Inhibiting Autophagy in Gastric Cancer Cells. (PubMed, J Oncol) - "Importantly, APY0201 was also effective in inducing repression of autophagy and cell cycle arrest in the mouse tumor xenograft. Our results suggest that APY0201 could be a new promising therapeutic option for GC."

Journal • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

PIK-001 a Novel Small Molecule Inhibitor of Pikfyve for Treatment of Multiple Myeloma (MM) (ASH 2021) - "One panel drug APY-0201 and related drugs such as apilimod were initially developed as suppressors of production of interleukin (IL)-12 and IL-23 production and entered clinical trials for inflammatory diseases but subsequently were found to be primary inhibitors of PikFyve. Preliminary murine studies with PIK001 have shown high efficacy in preventing myeloma growth using a transplantable VKappa*myc cell line and daily oral delivery of drug. This pre-clinical data sets the stage for future clinical testing."

Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology • Pancreatic Cancer • Solid Tumor • Transplantation • IL12A • MYC • SDC1

Identification of PIKfyve kinase as a target in multiple myeloma. (PubMed, Haematologica) - "The broad anti- multiple myeloma activity of PIKfyve inhibitors was further demonstrated in confirmatory screens and showed the superior potency of APY0201 when compared to the PIKfyve inhibitors YM201636 and apilimod, with a mid-point EC50 at nanomolar concentrations respectively in 65%, 40%, and 5% of the tested cell lines. Furthermore, we established an assay measuring autophagy as a predictive marker of APY0201 sensitivity. Overall, these findings suggest promising activity of PIKfyve inhibitors secondary to disruption of autophagy in multiple myeloma and a strategy to enrich for likely responders."

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