Unknown

Dataset Information

0

Identification of novel pyrrolopyrimidine and pyrrolopyridine derivatives as potent ENPP1 inhibitors.

ABSTRACT: 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.

SUBMITTER: Jeong HJ 

PROVIDER: S-EPMC9467556 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Identification of novel pyrrolopyrimidine and pyrrolopyridine derivatives as potent ENPP1 inhibitors.

Jeong Hee Jin HJ   Lee Hye Lim HL   Kim Sung Joon SJ   Jeong Jeong Hyun JH   Ji Su Hyun SH   Kim Han Byeol HB   Kang Miso M   Chung Hwan Won HW   Park Chan Sun CS   Choo Hyunah H   Yoon Hyo Jae HJ   Kim Nam-Jung NJ   Lee Duck-Hyung DH   Lee Sang Hee SH   Han Seo-Jung SJ  

Journal of enzyme inhibition and medicinal chemistry 20221201 1

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 <b>18p</b> possessed high potency (IC<sub>50</sub> = 25.0 nM) against ENPP1, and activated STING pathway in a concentration dependent manner. Also, in r  ...[more]

Similar Datasets

Unknown Computer aided designing of novel pyrrolopyridine derivatives as JAK1 inhibitors.
| S-EPMC8630053 | biostudies-literature
Unknown Identification of novel piperazinylquinoxaline derivatives as potent phosphoinositide 3-kinase (PI3K) inhibitors.
| S-EPMC3419191 | biostudies-literature
Unknown Identification of Novel Thiazolo[5,4-b]Pyridine Derivatives as Potent Phosphoinositide 3-Kinase Inhibitors.
| S-EPMC7594053 | biostudies-literature
Unknown Potent Pyrimidine and Pyrrolopyrimidine Inhibitors of Testis-Specific Serine/Threonine Kinase 2 (TSSK2).
| S-EPMC5962959 | biostudies-literature
Unknown Identification of novel phenylalanine derivatives bearing a hydroxamic acid moiety as potent quorum sensing inhibitors.
| S-EPMC11042162 | biostudies-literature
Unknown QSAR modelling, molecular docking, molecular dynamic and ADMET prediction of pyrrolopyrimidine derivatives as novel Bruton's tyrosine kinase (BTK) inhibitors.
| S-EPMC10788635 | biostudies-literature
Unknown Novel amino-β-lactam derivatives as potent cholesterol absorption inhibitors.
| S-EPMC4237514 | biostudies-literature
Unknown Novel curcumin derivatives as potent inhibitors of amyloid β aggregation.
| S-EPMC5669405 | biostudies-literature
Unknown Optimization of a Novel Mandelamide-Derived Pyrrolopyrimidine Series of PERK Inhibitors.
| S-EPMC9611727 | biostudies-literature
Unknown Synthesis and Identification of Novel Berberine Derivatives as Potent Inhibitors against TNF-α-Induced NF-κB Activation.
| S-EPMC6152030 | biostudies-literature