Ji, Su Hyun Kang, Miso Ahn, Hyomin Baek, Soo Yeon Lee, In-Gyun Jeon, Janul Chung, Hwan Won Han, Dong Kyun Yang, Seoyeong Lee, Hyebin Kim, Yeseul Wi, Ji Hun Lee, Jee Hee Yoo, Younghoon Kang, Sungbae Jang, Mihue Jeon, Byungsun Kim, Nam-Jung Song, Chiman Lee, Sanghee Han, Seo-Jung 2025-07-28T05:00:06Z 2025-07-28T05:00:06Z 2025-07-26 2025-08 0022-2623 https://pubs.kist.re.kr/handle/201004/152845 A novel small-molecule ENPP1 inhibitor, compound 31 featuring a pyrrolopyrimidinone core, was identified. Compound 31 exhibited potent ENPP1 inhibition with an IC50 of 14.68 nM and effectively activated the STING pathway in cell lines. In addition, 31 promoted cytokine release, thereby enhancing innate immune response. Moreover, 31 demonstrated favorable ADMET properties. Compound 31 displayed significant antitumor efficacy in 4T1 and CT26 syngeneic mouse models without notable toxicity. These findings highlight the potential of 31 as a promising compound for cancer immunotherapy by enhancing STING-mediated immune activation and improving responses to immune checkpoint inhibitors. English American Chemical Society Identification of 5,7-Dihydro-6 H-pyrrolo[2,3- d]pyrimidin-6-one Derivatives as ENPP1 Inhibitors for STING Pathway-Mediated Immunotherapy Article 10.1021/acs.jmedchem.5c01021 1 Journal of Medicinal Chemistry, v.68, no.15, pp.16059 - 16075 Journal of Medicinal Chemistry 68 15 16059 16075 N scie scopus 001537086000001 Chemistry, Medicinal Pharmacology & Pharmacy Article