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Development of Small-Molecule STING Activators for Cancer Immunotherapy
- Source :
- Biomedicines, Vol 10, Iss 1, p 33 (2021)
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- In cancer immunotherapy, the cyclic GMP–AMP synthase–stimulator of interferon genes (STING) pathway is an attractive target for switching the tumor immunophenotype from ‘cold’ to ‘hot’ through the activation of the type I interferon response. To develop a new chemical entity for STING activator to improve cyclic GMP-AMP (cGAMP)-induced innate immune response, we identified KAS-08 via the structural modification of DW2282, which was previously reported as an anti-cancer agent with an unknown mechanism. Further investigation revealed that direct STING binding or the enhanced phosphorylation of STING and downstream effectors were responsible for DW2282-or KAS-08-mediated STING activity. Furthermore, KAS-08 was validated as an effective STING pathway activator in vitro and in vivo. The synergistic effect of cGAMP-mediated immunity and efficient anti-cancer effects successfully demonstrated the therapeutic potential of KAS-08 for combination therapy in cancer treatment.
Details
- Language :
- English
- ISSN :
- 10010033 and 22279059
- Volume :
- 10
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Biomedicines
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.beb9309e5e44ec4b35bde18670bf92a
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/biomedicines10010033