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更新于：2026-01-24

PP4(University of Florida)

更新于：2026-01-24

概要

概要

基本信息

药物类型

蛋白水解靶向嵌合体（PROTAC）

别名

PP4

靶点

Bcl-xl

作用方式

降解剂

作用机制

Bcl-xl 降解剂(Bcl-X蛋白降解剂)

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构-

在研机构

University of Florida

非在研机构-

权益机构-

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-

结构/序列

分子式C79H100ClF3N10O11S4

InChIKeyMUEPNUZWMIAHRW-UWPVXNPMSA-N

CAS号-

关联

100 项与 PP4(University of Florida) 相关的临床结果

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100 项与 PP4(University of Florida) 相关的转化医学

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100 项与 PP4(University of Florida) 相关的专利（医药）

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项与 PP4(University of Florida) 相关的文献（医药）

2025-06-01·PLANT FOODS FOR HUMAN NUTRITION

Pea Peptide Modulates Abnormal Aβ Production in PC12 Cells Induced by Lead Exposure

Article

作者: Yang, Huijie ; Cheng, Yongxia ; Cui, Ningning ; Galaverna, Gianni ; Huang, Xianqing ; Song, Lianjun ; Hai, Dan ; Zhao, Guangshan ; Qiao, Mingwu ; Li, Ning ; Bakry, Ibrahim A ; Ma, Yan

Lead (Pb) exposure poses significant health risks, particularly in neurodegenerative diseases such as Alzheimer's disease (AD). This study investigates the neuroprotective effects of pea peptide (PP4) on PC12 cells exposed to Pb. Using Cell Counting Kit-8 (CCK-8), pretreatment with PP4 at 50 and 200 µM concentrations significantly improved cell viability compared to Pb-only treated cells (P < 0.05), indicating a protective effect. Moreover, Pb exposure led to increased Amyloid Precursor Protein (APP) expression at 10 and 20 µM after 24 h (P < 0.05), while β-site amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) levels were elevated across all concentrations tested (P < 0.05). We established that PP4 can mitigate Pb-induced cytotoxicity and reduce the expression of APP and BACE1 by activating the Phosphoinositide 3-kinase / Protein Kinase (PI3K/AKT) signaling pathway. This study highlights the potential of PP4 as a therapeutic agent in preventing neurotoxic damage associated with lead exposure, suggesting a novel approach for the management of AD.

2025-03-01·PLANT FOODS FOR HUMAN NUTRITION

Pea Peptides and Heavy Metal Neurotoxicity: Exploring Mechanisms and Mitigation Strategies in PC12 Cells

Article

作者: Cheng, Yongxia ; Li, Qian ; Yang, Huijie ; Cui, Ningning ; Wang, Fangyu ; Galaverna, Gianni ; Bakry, Ibrahim A ; Li, Ning ; Zhao, Peijun ; Li, Tiange

Calsyntenin-1 (Clst1) is a sensitive indicator of lead (Pb) toxicity in neural tissue. This study was designed to investigate the impact of lead exposure on Clst1 expression in PC12 cells and the mitigating effect of pea peptide 4 (PP4) on lead-induced neurotoxicity. Data showed that lead exposure, at varying doses and durations, disrupted the mRNA expression and protein levels of Clstn1 in PC12 cells. However, immunofluorescence results showed that treatment with PP4 significantly increased Clstn1 protein expression in the Pb + PP4 and PP4 groups compared to the Pb groups (P < 0.05). Lead exposure activates the JNK and p38 pathways; at the same time, PP4 treatment enhances ERK pathway activation and reduces JNK and p38 activation.

2021-10-14·Journal of medicinal chemistry1区 · 医学

Discovery of a Novel BCL-X_L PROTAC Degrader with Enhanced BCL-2 Inhibition

1区 · 医学

Article

作者: Poddar, Saikat K. ; Thummuri, Dinesh ; Lv, Dongwen ; Hua, Nan ; Hu, Wanyi ; Zhang, Peiyi ; Yuan, Yaxia ; Pal, Pratik ; Zhang, Xuan ; Khan, Sajid ; Liu, Xingui ; Zheng, Guangrong ; Zhou, Daohong

BCL-X_L and BCL-2 are important targets for cancer treatment. BCL-X_L specific proteolysis-targeting chimeras (PROTACs) have been developed to circumvent the on-target platelet toxicity associated with BCL-X_L inhibition. However, they have minimal effects on cancer cells that are dependent on BCL-2 or both BCL-X_L and BCL-2. Here we report a new series of BCL-PROTACs. The lead PZ703b exhibits high potency in inducing BCL-X_L degradation and in inhibiting but not degrading BCL-2, showing a hybrid dual-targeting mechanism of action that is unprecedented in a PROTAC molecule. As a result, PZ703b is highly potent in killing BCL-X_L dependent, BCL-2 dependent, and BCL-X_L/BCL-2 dual-dependent cells in an E3 ligase (VHL)-dependent fashion. We further found that PZ703b forms stable {BCL-2:PROTAC:VCB} ternary complexes in live cells that likely contribute to the enhanced BCL-2 inhibition by PZ703b. With further optimization, analogues of PZ703b could potentially be developed as effective antitumor agents by co-targeting BCL-X_L and BCL-2.

100 项与 PP4(University of Florida) 相关的药物交易

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