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Identification of novel pyrrolopyrimidine and pyrrolopyridine derivatives as potent ENPP1 inhibitors

التفاصيل البيبلوغرافية
العنوان: Identification of novel pyrrolopyrimidine and pyrrolopyridine derivatives as potent ENPP1 inhibitors
المؤلفون: Hee Jin Jeong, Hye Lim Lee, Sung Joon Kim, Jeong Hyun Jeong, Su Hyun Ji, Han Byeol Kim, Miso Kang, Hwan Won Chung, Chan Sun Park, Hyunah Choo, Hyo Jae Yoon, Nam-Jung Kim, Duck-Hyung Lee, Sanghee Lee, Seo-Jung Han
المصدر: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 37, Iss 1, Pp 2434-2451 (2022)
بيانات النشر: Taylor & Francis Group, 2022.
سنة النشر: 2022
المجموعة: LCC:Therapeutics. Pharmacology
مصطلحات موضوعية: ENPP1, STING, innate immunity, cancer immunotherapy, Therapeutics. Pharmacology, RM1-950
الوصف: 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-β 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 14756366
1475-6374
1475-6366
Relation: https://doaj.org/toc/1475-6366; https://doaj.org/toc/1475-6374
DOI: 10.1080/14756366.2022.2119566
URL الوصول: https://doaj.org/article/d4014599d664477e9c2a28b353c2de49
رقم الأكسشن: edsdoj.4014599d664477e9c2a28b353c2de49
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:14756366
14756374
DOI:10.1080/14756366.2022.2119566