2. Academic Validation
  3. Discovery of KBD4466, a Selective TLR 7/8 Inhibitor, for the Treatment of Autoimmune Diseases

Discovery of KBD4466, a Selective TLR 7/8 Inhibitor, for the Treatment of Autoimmune Diseases

  • J Med Chem. 2025 Jul 24;68(14):14537-14554. doi: 10.1021/acs.jmedchem.5c00656.
Yonghai Yuan 1,  Yonggang Wei 1,  Zhilong Jia 1,  Hongzhu Chu 1,  Dejiang Kong 1,  Feiquan Lei 1,  Fei Ye 1,  Xinying Qian 1,  Jing Zhang 1,  Xibing Zhou 1,  Xinying Zhu 1,  Zhiyong Li 1,  Xueya Liang 1,  Wei Chen 1
Affiliations

Affiliation

  • 1 Kangbaida (Sichuan) Biotechnology Co., Ltd., No. 14, Tianshun Street, Huayang Street, Tianfu New District, Chengdu 610213, China.
PMID: 40591919 DOI: 10.1021/acs.jmedchem.5c00656
Abstract

The Toll-like Receptor (TLR) family comprises a class of proteins that play a critical role in the innate immune system. Toll-like receptors TLR7 and TLR8 are transmembrane receptors that recognize single-stranded RNA. Aberrant activation of TLR7/8 is associated with the progression of certain autoimmune diseases, such as lupus. Therefore, highly selective inhibitors of TLR7/8 would be an effective therapeutic approach. Here, we have discovered a small molecule inhibitor, KBD4466 (19), which demonstrates excellent cellular activity, favorable pharmacokinetic properties, potent inhibition of cytokine production in mouse pharmacodynamic studies, and outstanding therapeutic efficacy in an SLE animal model. Furthermore, we have developed an efficient synthetic route to access a [3.1.0] bicyclic system featuring chiral contiguous quaternary carbon centers.

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