An updated patent review of stimulator of interferon genes agonists (2021 - present).

INTRODUCTION: Stimulator of Interferon Genes (STING) is an innate immune sensor. Activation of STING triggers a downstream response that results in the expression of proinflammatory cytokines (TNF-α, IL-1ß) via nuclear factor kappa-B (NF-κB) or the expression of type I interferons (IFNs) via an interferon regulatory factor 3 (IRF3). IFNs can eventually result in promotion of the adaptive immune response including activation of tumor-specific CD8+ T cells to abolish the tumor. Consequently, activation of STING has been considered as a potential strategy for cancer treatment. AREAS COVERED: This article provides an overview on structures and pharmacological data of CDN-like and non-nucleotide STING agonists acting as anticancer agents (January 2021 to October 2023) from a medicinal chemistry perspective. The data in this review come from EPO, WIPO, RCSB PDB, CDDI. EXPERT OPINION: In recent years, several structurally diverse STING agonists have been identified. As an immune enhancer, they are used in the treatment of tumors, which has received extensive attention from scientific community and pharmaceutical companies. Despite the multiple challenges that have appeared, STING agonists may offer opportunities for immunotherapy.

Development of Orally Bioavailable Amidobenzimidazole Analogues Targeting Stimulator of Interferon Gene (STING) Receptor.

Stimulator of interferon gene (STING) is a critical adaptor protein that has a pivotal role in triggering inherent immune responses to infection. STING-linked interferon production has been involved in anti-inflammation, anti-infection, and antitumor immunity. Herein, a series of amidobenzimidazole analogues as STING agonists were profiled for potency and drug-like properties. By structure-based modification and optimization based on mono-aminobenzimidazole (ABZI), analogues with nanomolar STING agonistic activities were obtained. Among them, compounds D59 and D61 significantly increased the transcription of IFN-ß and proinflammatory cytokine CXCL10, as well as dramatically induced the phosphorylation of STING downstream proteins in THP1 cells. Furthermore, compound D61 exhibited favorable pharmacokinetic properties and metabolic stabilities. In a CT-26 syngeneic mice-bearing tumor model, D61 effectively inhibited tumor growth with good tolerance when administered via intratumoral, intravenous, intraperitoneal, and oral routes. This research on orally bioavailable amidobenzimidazole analogues expands the diversity of chemical structures of agonists for STING-mediated immunotherapy.

[Effects of different proportions of red and blue light on the growth and photosynthesis of tomato seedlings]. / ä¸åŒæ¯”ä¾‹çº¢è“å ‰å¯¹ç•ªèŒ„å¹¼è‹—ç”Ÿé•¿å’Œå ‰åˆä½œç”¨çš„å½±å“.

In order to explore the mechanism of response of growth and development of tomato seedlings to the combination of red and blue light, the light-emitting-diodes (LEDs) as precision modulation light sources were used in this study with 7 treatments including red (R) light, blue (B) light and combination of R+B light (9R1B, 6R1B, 3R1B, 1R1B, 1R3B), white (W) light as control, and the effects of different proportions of R and B light on the growth, photosynthetic pigment content, photosynthetic characteristics, chlorophyll fluorescence and root activity of tomato seedlings with variety of 'SV0313TG' as experiment material were studied. The results showed that there were significant differences in growth of tomato seedlings under treatments of different proportions of R and B light. The plant height, specific leaf area and intercellular CO2 concentration of tomato seedlings were significantly promoted by R light, while Fv/Fm and χPS2 were decreased, the root growth was inhibited as the root activity declined, so that the seedling index was reduced. The seedling growth was significantly suppressed under B light and the chlorophyll content was decreased, while the chlorophyll a/b was enhanced. Furthermore, combination of R+B light was be-neficial to the growth and development of tomato seedlings, and the plant dry mass, chlorophyll content and photosynthetic performance were significantly increased under 3R1B. In addition, seedlings grew strongly and had the highest value of seedling index under this treatment. In conclusion, the combination of R+B light could promote photosynthetic pigment content and photosynthetic efficiency in leaves of tomato seedlings, as well as plant growth, especially for treatment of 3R1B.