Crosstalk between innate and adaptive immunities has emerged as a promising anticancer strategy. Notably, the stimulator of interferon genes (STING) pathway and its mediated proteins, including ENPP and PARP (Figure 1), are predominantly involved in innate immune responses, possessing high therapeutic potential for new immunotherapeutics development. And Eurofins Discovery has developed tools to access that potential.
Figure 1. STING pathway activation and regulation. STING agonist cGAMP, a cyclic dinucleotide (CDN), interacts with STING protein to induce the transcription of interferon (IFN) genes and other cytokines. ENPP1 and PARP7 inhibit pathway activation by hydrolyzing cGAMP or inhibiting downstream signaling cascade, respectively.
Eurofins Discovery offers three specialized panels for STING, ENPP, and PARP. These drug screening platforms are well-validated, robust, and reproducible, providing seamless assessments of different variants and broad subtypes.
- STING Human Variant LeadHunter® Panel is a cell-based STING agonist reporter assay covering common human STING variants (Figure 2A). It provides the most efficient way to evaluate potency and selectivity simultaneously.
- ENPP Screen LeadHunter Panel offers the most comprehensive enzymatic ENPP assays in the market, covering all ENPP subtypes from ENPP1 to ENPP7. It enables enabling the assessment of potency and the design of highly selective compounds against specific ENPP targets (Figure 2B).
- PARP Screen LeadHunter Panel contains PARP1, PARP2, PARP3, PARP5A, PARP5B, and PARP7 assays (Figure 2C), which facilitates screening out selective and potent compounds not only targeting innate immunity but also other different cancer treatment strategies.
Figure 2. Demonstrative data of STING variant panel (A.), ENPP panel (B.), and PARP panel (C.). A. The diABZI is a non-CDN STING agonist that has shown different potencies against human STING WT and variants. B. ENPP1 inhibitor ENPP1-IN-1 was validated through the ENPP panel and showed high potency and selectivity against ENPP1 among other ENPP subtypes. C. PARP7 inhibitor RBN-2397 exhibited diverse inhibition profiles with high selectivity against PARP7 and PARP2. *Indicates < 50% inhibition at 100 µM.
