The discovery of potent small molecule cyclic urea activators of STING

  • Eur J Med Chem. 2022 Feb 5;229:114087. doi: 10.1016/j.ejmech.2021.114087.
Sourav Basu  1 ,  Sandip Middya  1 ,  Monali Banerjee  1 ,  Rajib Ghosh  1 ,  David C Pryde  2 ,  Dharmendra B Yadav  1 ,  Ritesh Shrivastava  1 ,  Arjun Surya  3
Affiliations
  • 1. Curadev Pharma Pvt. Ltd., B-87, Sector 83, Noida, 201305, Uttar Pradesh, India.
  • 2. Curadev Pharma Ltd., Innovation House, Discovery Park, Ramsgate Road, Sandwich, Kent, CT13 9ND, UK.
  • 3. Curadev Pharma Pvt. Ltd., B-87, Sector 83, Noida, 201305, Uttar Pradesh, India. Electronic address: [email protected].
PMID: 34998056 DOI: 10.1016/j.ejmech.2021.114087
Abstract

STING mediates innate immune responses that are triggered by the presence of cytosolic DNA. Activation of STING to boost antigen recognition is a therapeutic modality that is currently being tested in Cancer patients using nucleic-acid based macrocyclic STING ligands. We describe here the discovery of 3,4-dihydroquinazolin-2(1H)-one based 6,6-bicyclic heterocyclic agonists of human STING that activate all known human variants of STING with high potency.

Keywords
Immune oncology; Innate immunity; Interferon; STING; cGAS.
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