Nef-directed PROTACs(University of Pittsburgh School of Medicine)(Nef-directed PROTACs(University of Pittsburgh School of Medicine))

概要

基本信息

药物类型

蛋白水解靶向嵌合体（PROTAC）

别名-

靶点

HIV-1 nef

作用机制

HIV-1 nef调节剂(HIV-1 Nef蛋白调节剂)

治疗领域

免疫系统疾病感染泌尿生殖系统疾病

在研适应症

HIV感染

非在研适应症-

原研机构

The Fox Chase Cancer Center

University of Pittsburgh School of Medicine

在研机构

University of Pittsburgh School of Medicine

The Fox Chase Cancer Center

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 Nef-directed PROTACs(University of Pittsburgh School of Medicine) 相关的临床结果

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100 项与 Nef-directed PROTACs(University of Pittsburgh School of Medicine) 相关的转化医学

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100 项与 Nef-directed PROTACs(University of Pittsburgh School of Medicine) 相关的专利（医药）

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1

项与 Nef-directed PROTACs(University of Pittsburgh School of Medicine) 相关的文献（医药）

2025-01-01·Bioactive Materials

Self-assembled PROTACs enable protein degradation to reprogram the tumor microenvironment for synergistically enhanced colorectal cancer immunotherapy

Article

作者: Ren, Maomao ; Luan, Xin ; Chen, Hongzhuan ; Zhang, Chunling ; Jin, Jinmei ; Zhang, Weidong ; Lu, Xinchen ; Wu, Ye ; Lin, Jiayi ; Lu, Shengxin ; Zhang, Xiaokun ; Zhang, Jiyuan

Both β-catenin and STAT3 drive colorectal cancer (CRC) growth, progression, and immune evasion, and their co-overexpression is strongly associated with a poor prognosis. However, current small molecule inhibitors have limited efficacy due to the reciprocal feedback activation between STAT3 and β-catenin. Inspired by the PROteolysis TArgeting Chimera (PROTAC), a promising pharmacological modality for the selective degradation of proteins, we developed a strategy of nanoengineered peptide PROTACs (NP-PROTACs) to degrade both β-catenin and STAT3 effectively. The NP-PROTACs were engineered by coupling the peptide PROTACs with DSPE-PEG via disulfide bonds and self-assembled into nanoparticles. Notably, the dual degradation of β-catenin and STAT3 mediated by NP-PROTACs led to a synergistic antitumor effect compared to single-target treatment. Moreover, NP-PROTACs treatment enhanced CD103⁺ dendritic cell infiltration and T-cell cytotoxicity, alleviating the immunosuppressive microenvironment induced by β-catenin/STAT3 in CRC. These results highlight the potential of NP-PROTACs in facilitating the simultaneous degradation of two pathogenic proteins, thereby providing a novel avenue for cancer therapy.

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