2. Academic Validation
  3. M335, a novel small-molecule STING agonist activates the immune response and exerts antitumor effects

M335, a novel small-molecule STING agonist activates the immune response and exerts antitumor effects

  • Eur J Med Chem. 2024 Jan 15:264:116018. doi: 10.1016/j.ejmech.2023.116018.
Man Zhao 1,  Weizhen Fan 2,  Ying Wang 3,  Pengfei Qiang 2,  Zhihua Zheng 2,  Hao Shan 2,  Ming Zhang 2,  Pengyutian Liu 3,  Yao Wang 2,  Guofeng Li 4,  Min Li 5,  Liang Hong 6
Affiliations

Affiliations

  • 1 Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China; School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518055, China.
  • 2 Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
  • 3 School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518055, China.
  • 4 School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518055, China. Electronic address: liguofeng@szu.edu.cn.
  • 5 Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China. Electronic address: limin65@mail.sysu.edu.cn.
  • 6 Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China. Electronic address: hongliang@sysu.edu.cn.
PMID: 38091891 DOI: 10.1016/j.ejmech.2023.116018
Abstract

In the context of antitumor immune responses, the activation of the stimulator of interferon genes (STING) assumes a critical role and imparts enhanced immunogenicity. An effective strategy for exogenously activating the immune system involves the utilization of STING agonists, and prior investigations primarily concentrated on modifying endogenous cyclic dinucleotides (CDNs) to achieve this. Nevertheless, the practical utility of CDNs was restricted due to limitations associated with their physicochemical attributes and administration protocols. In this article, we present the discovery of a novel small-molecule agonist denoted as M335, identified through high-throughput screening using surface plasmon resonance (SPR). M335 demonstrates the ability to activate the TBK1-IRF3-IFN axis in a STING-dependent manner in vitro. Through experimentation on mouse models bearing tumors, we observed that the administration of M335 resulted in the activation of immune cells. Notably, significant antitumor effects were achieved with both intratumoral and intraperitoneal administration of M335. These findings suggest the potential of M335 as a promising agent for Cancer Immunotherapy, which will promote the development of STING agonists in anti-tumor applications.

Keywords

Antitumor effects; Immunotherapy; STING agonist; Small-molecule compounds.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z