2. Academic Validation
  3. Discovery and optimization of pyrazolopyrimidine sulfamates as ATG7 inhibitors

Discovery and optimization of pyrazolopyrimidine sulfamates as ATG7 inhibitors

  • Bioorg Med Chem. 2020 Oct 1;28(19):115681. doi: 10.1016/j.bmc.2020.115681.
Shih-Chung Huang 1,  Sharmila Adhikari 2,  James E Brownell 2,  Emily F Calderwood 2,  Jouhara Chouitar 2,  Natalie Roy D'Amore 2,  Dylan B England 2,  Klaudia Foley 2,  Sean J Harrison 2,  Patrick J LeRoy 2,  David Lok 2,  Anna Lublinsky 2,  Li-Ting Ma 2,  Saurabh Menon 2,  Yu Yang 2,  Ji Zhang 2,  Alexandra E Gould 2
Affiliations

Affiliations

  • 1 Takeda Pharmaceuticals International Co., 40 Landsdowne Street, Cambridge, MA 02139, United States. Electronic address: sampson.huang@takeda.com.
  • 2 Takeda Pharmaceuticals International Co., 40 Landsdowne Street, Cambridge, MA 02139, United States.
PMID: 32912429 DOI: 10.1016/j.bmc.2020.115681
Abstract

Autophagy is postulated to be required by Cancer cells to survive periods of metabolic and/or hypoxic stress. Atg7 is the E1 Enzyme that is required for activation of Ubl conjugation pathways involved in autophagosome formation. This article describes the design and optimization of pyrazolopyrimidine sulfamate compounds as potent and selective inhibitors of Atg7. Cellular levels of the Autophagy markers, LC3B and NBR1, are regulated following treatment with these compounds.

Keywords

ATG7; ATG7 inhibitor; Autophagy; E1 enzyme.

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