Jeong, Hee Jin Lee, Hye Lim Kim, Sung Joon Jeong, Jeong Hyun Ji, Su Hyun Kim, Han Byeol Kang, Miso Chung, Hwan Won Park, Chan Sun Choo, Hyunah Yoon, Hyo Jae Kim, Nam-Jung Lee, Duck-Hyung Lee, Sang Hee Han, Seo-Jung 2024-01-19T10:33:45Z 2024-01-19T10:33:45Z 2022-09-15 2022-12 1475-6366 https://pubs.kist.re.kr/handle/201004/114270 In an effort to discover novel scaffolds of non-nucleotide-derived Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) inhibitors to stimulate the Stimulator of Interferon Genes (STING) pathway, we designed and synthesised pyrrolopyrimidine and pyrrolopyridine derivatives and performed structure-activity relationship (SAR) study. We found 18p possessed high potency (IC50 = 25.0 nM) against ENPP1, and activated STING pathway in a concentration dependent manner. Also, in response to STING pathway activation, cytokines such as IFN-beta and IP-10 were induced by 18p in a concentration dependent manner. Finally, we discovered that 18p causes inhibition of tumour growth in 4T1 syngeneic mouse model. This study provides new insight into the designing of novel ENPP1 inhibitors and warrants further development of small molecule immune modulators for cancer immunotherapy. English Taylor & Francis Identification of novel pyrrolopyrimidine and pyrrolopyridine derivatives as potent ENPP1 inhibitors Article 10.1080/14756366.2022.2119566 1 Journal of Enzyme Inhibition and Medicinal Chemistry, v.37, no.1, pp.2434 - 2451 Journal of Enzyme Inhibition and Medicinal Chemistry 37 1 2434 2451 Y scie scopus 000850701000001 Biochemistry & Molecular Biology Chemistry, Medicinal Biochemistry & Molecular Biology Pharmacology & Pharmacy Article PROTEIN NPP1 ENPP1 STING innate immunity cancer immunotherapy