Identification of novel pyrrolopyrimidine and pyrrolopyridine derivatives as potent ENPP1 inhibitors

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, Sang Hee Lee, Seo Jung Han

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


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.

Original languageEnglish
Pages (from-to)2434-2451
Number of pages18
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Issue number1
Publication statusPublished - 2022


  • ENPP1
  • cancer immunotherapy
  • innate immunity

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery


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