GNS561 | PPT1 inhibitor/STING activator

GNS561 chemical structure

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GNS561 (1914148-73-4) induces lysosomal dysregulation leading to inhibition of autophagy.1 It displayed efficacy against intrahepatic cholangiocarcinoma1 and hepatocellular carcinoma2. GNS561 acted as an anti-fibrotic agent against liver fibrosis in a rat model.3 GNS561-induced cell death is partially caused by inhibition of palmitoyl-protein thioesterase 1 (PPT1) leading to lysosomal dysfunction.4 GNS561 treatment of prostate and ovarian cancer models enhanced STING expression and activation via PPT1 inhibition leading to infiltration of cytotoxic T cells.5  GNS561 represents a potentially novel immunotherapy for cold tumors.

References/Citations:

  1. Brun et al. (2019), GNS561, a new lysosomotropic small molecule, for the treatment of intrahepatic cholangiocarcinoma; Invest. New Drugs, 37 1135
  2. Brun et al. (2021), GNS561, a New Autophagy Inhibitor Active against Cancer Stem Cells in Hepatocellular Carcinoma and Hepatic Metastasis from Colorectal Cancer; J. Cancer, 12 5432
  3. Bestion et al. (2020), GNS561 acts as a potent anti-fibrotic and pro-fibrolytic agent in liver fibrosis through TGF-ß1 inhibition; Adv. Chronic Dis., 11 2040622320942042
  4. Brun et al. (2022), GNS561, a clinical-stage PPT1 inhibitor, is efficient against hepatocellular carcinoma via modulation of lysosomal functions; Autophagy, 18 678
  5. Chowdhury et al. (2025), PPT1 is a negative regulator of STING signaling in cancer cells and its inhibition reactivates immune surveillance in cold tumors; Proc. Natl. Acad. Sci. USA, 122 e2514948122
1914148-72-3, 1914148-73-4, cold tumor immunotherapy, Ezurpimtrostat, GNS-561, GNS561, GNS561 supplier, STING enhancer
Alternate Name:
Ezurpimtrostat

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GNS561 (1914148-73-4) induces lysosomal dysregulation leading to inhibition of autophagy.1 It displayed efficacy against intrahepatic cholangiocarcinoma1 and hepatocellular carcinoma2. GNS561 acted as an anti-fibrotic agent against liver fibrosis in a rat model.3 GNS561-induced cell death is partially caused by inhibition of palmitoyl-protein thioesterase 1 (PPT1) leading to lysosomal dysfunction.4 GNS561 treatment of prostate and ovarian cancer models enhanced STING expression and activation via PPT1 inhibition leading to infiltration of cytotoxic T cells.5  GNS561 represents a potentially novel immunotherapy for cold tumors.

References/Citations:

  1. Brun et al. (2019), GNS561, a new lysosomotropic small molecule, for the treatment of intrahepatic cholangiocarcinoma; Invest. New Drugs, 37 1135
  2. Brun et al. (2021), GNS561, a New Autophagy Inhibitor Active against Cancer Stem Cells in Hepatocellular Carcinoma and Hepatic Metastasis from Colorectal Cancer; J. Cancer, 12 5432
  3. Bestion et al. (2020), GNS561 acts as a potent anti-fibrotic and pro-fibrolytic agent in liver fibrosis through TGF-ß1 inhibition; Adv. Chronic Dis., 11 2040622320942042
  4. Brun et al. (2022), GNS561, a clinical-stage PPT1 inhibitor, is efficient against hepatocellular carcinoma via modulation of lysosomal functions; Autophagy, 18 678
  5. Chowdhury et al. (2025), PPT1 is a negative regulator of STING signaling in cancer cells and its inhibition reactivates immune surveillance in cold tumors; Proc. Natl. Acad. Sci. USA, 122 e2514948122