ENPP1, an Old Enzyme with New Functions, and Small Molecule Inhibitors—A STING in the Tale of ENPP1
Ectonucleotide pyrophosphatase/phosphodiesterase I (ENPP1) was identified several decades ago as a type II transmembrane glycoprotein with nucleotide pyrophosphatase and phosphodiesterase enzymatic activities, critical for purinergic signaling. Recently, ENPP1 has emerged as a critical phosphodieste...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-11-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/24/22/4192 |
| _version_ | 1817993770086432768 |
|---|---|
| author | Kenneth I. Onyedibe Modi Wang Herman O. Sintim |
| author_facet | Kenneth I. Onyedibe Modi Wang Herman O. Sintim |
| author_sort | Kenneth I. Onyedibe |
| collection | DOAJ |
| description | Ectonucleotide pyrophosphatase/phosphodiesterase I (ENPP1) was identified several decades ago as a type II transmembrane glycoprotein with nucleotide pyrophosphatase and phosphodiesterase enzymatic activities, critical for purinergic signaling. Recently, ENPP1 has emerged as a critical phosphodiesterase that degrades the stimulator of interferon genes (STING) ligand, cyclic GMP−AMP (cGAMP). cGAMP or analogs thereof have emerged as potent immunostimulatory agents, which have potential applications in immunotherapy. This emerging role of ENPP1 has placed this “old” enzyme at the frontier of immunotherapy. This review highlights the roles played by ENPP1, the mechanism of cGAMP hydrolysis by ENPP1, and small molecule inhibitors of ENPP1 with potential applications in diverse disease states, including cancer. |
| first_indexed | 2024-04-14T01:44:11Z |
| format | Article |
| id | doaj.art-a57e8569383f45d8a62bf2d3c65d0e91 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-14T01:44:11Z |
| publishDate | 2019-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a57e8569383f45d8a62bf2d3c65d0e912022-12-22T02:19:37ZengMDPI AGMolecules1420-30492019-11-012422419210.3390/molecules24224192molecules24224192ENPP1, an Old Enzyme with New Functions, and Small Molecule Inhibitors—A STING in the Tale of ENPP1Kenneth I. Onyedibe0Modi Wang1Herman O. Sintim2Chemistry Department, Institute for Drug Discovery, Purdue University, West Lafayette, IN 47907, USAChemistry Department, Institute for Drug Discovery, Purdue University, West Lafayette, IN 47907, USAChemistry Department, Institute for Drug Discovery, Purdue University, West Lafayette, IN 47907, USAEctonucleotide pyrophosphatase/phosphodiesterase I (ENPP1) was identified several decades ago as a type II transmembrane glycoprotein with nucleotide pyrophosphatase and phosphodiesterase enzymatic activities, critical for purinergic signaling. Recently, ENPP1 has emerged as a critical phosphodiesterase that degrades the stimulator of interferon genes (STING) ligand, cyclic GMP−AMP (cGAMP). cGAMP or analogs thereof have emerged as potent immunostimulatory agents, which have potential applications in immunotherapy. This emerging role of ENPP1 has placed this “old” enzyme at the frontier of immunotherapy. This review highlights the roles played by ENPP1, the mechanism of cGAMP hydrolysis by ENPP1, and small molecule inhibitors of ENPP1 with potential applications in diverse disease states, including cancer.https://www.mdpi.com/1420-3049/24/22/4192cyclic dinucleotidecgampenpp1cancer |
| spellingShingle | Kenneth I. Onyedibe Modi Wang Herman O. Sintim ENPP1, an Old Enzyme with New Functions, and Small Molecule Inhibitors—A STING in the Tale of ENPP1 Molecules cyclic dinucleotide cgamp enpp1 cancer |
| title | ENPP1, an Old Enzyme with New Functions, and Small Molecule Inhibitors—A STING in the Tale of ENPP1 |
| title_full | ENPP1, an Old Enzyme with New Functions, and Small Molecule Inhibitors—A STING in the Tale of ENPP1 |
| title_fullStr | ENPP1, an Old Enzyme with New Functions, and Small Molecule Inhibitors—A STING in the Tale of ENPP1 |
| title_full_unstemmed | ENPP1, an Old Enzyme with New Functions, and Small Molecule Inhibitors—A STING in the Tale of ENPP1 |
| title_short | ENPP1, an Old Enzyme with New Functions, and Small Molecule Inhibitors—A STING in the Tale of ENPP1 |
| title_sort | enpp1 an old enzyme with new functions and small molecule inhibitors a sting in the tale of enpp1 |
| topic | cyclic dinucleotide cgamp enpp1 cancer |
| url | https://www.mdpi.com/1420-3049/24/22/4192 |
| work_keys_str_mv | AT kennethionyedibe enpp1anoldenzymewithnewfunctionsandsmallmoleculeinhibitorsastinginthetaleofenpp1 AT modiwang enpp1anoldenzymewithnewfunctionsandsmallmoleculeinhibitorsastinginthetaleofenpp1 AT hermanosintim enpp1anoldenzymewithnewfunctionsandsmallmoleculeinhibitorsastinginthetaleofenpp1 |