Azurin-p28(Azurin-p28) - 药物靶点：p53_在研适应症：肿瘤_专利_临床

概要

基本信息

药物类型

合成多肽

别名

Azurin p28

靶点

p53

作用方式

调节剂

作用机制

p53调节剂(p53蛋白调节剂)

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症

脑癌中枢神经系统肿瘤脉络丛肿瘤+ [7]

原研机构

University of Illinois

在研机构

Southern Research Institute

非在研机构

National Cancer Institute

CDG Therapeutics, Inc.

University of Illinois

+ [1]

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

登录后查看时间轴

结构/序列

分子式C122H197N31O47S2

InChIKeyRFGPECAMUVWTJN-AWHPYGDNSA-N

CAS号897026-25-4

Sequence Code 165904

来源: *****

关联

2

项与 Azurin-p28 相关的临床试验

NCT01975116

/ Completed临床1期IIT

A Phase I Trial of p28 (NSC745104), a Non-HDM2 Mediated Peptide Inhibitor of p53 Ubiquitination in Pediatric Patients With Recurrent or Progressive CNS Tumors

This phase I trial studies the side effects and best dose of azurin-derived cell-penetrating peptide p28 (p28) in treating patients with recurrent or progressive central nervous system tumors. Drugs used in chemotherapy, such as azurin-derived cell-penetrating peptide p28, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

开始日期2013-08-01

申办/合作机构

National Cancer Institute

NCT00914914

/ Completed临床1期

A Phase I Trial of p28 (Cell Penetrating Peptide) in the Treatment of Refractory Solid Tumors

The purpose of this study is to evaluate the safety of an experimental drug (p28) as a treatment for certain advanced cancers which express a protein called p53 and which have not responded to prior treatment.

开始日期2009-04-01

申办/合作机构

CDG Therapeutics, Inc.

100 项与 Azurin-p28 相关的临床结果

登录后查看更多信息

100 项与 Azurin-p28 相关的转化医学

登录后查看更多信息

100 项与 Azurin-p28 相关的专利（医药）

登录后查看更多信息

44

项与 Azurin-p28 相关的文献（医药）

2024-09-02·Toxicology Research

Design and computational analysis of a novel Leptulipin-p28 fusion protein as a multitarget anticancer therapy in breast cancer

Article

作者: Nadeem, Tariq ; Bashir, Hamid ; Rehman, Hafiz Muhammad ; Khalid, Sania ; Al-Qassab, Yasamin ; Fatima, Tehreem ; Mubasher, Mian Muhammad ; Ahmad, Irfan ; Kalsoom, Maria

AbstractThe search for novel therapeutic agents to treat breast cancer has compelled the development of fusion proteins that synergize the functional benefits of different bioactive peptides. Leptulipin, derived from scorpion venom, exhibits antitumor properties. On the other hand, p28, a peptide from the bacterial protein azurin, enhances cell penetration. The current study investigated the design and computational evaluation of a Leptulipin-p28 fusion protein for breast cancer treatment. The amino acid sequences of Leptulipin and p28 were joined via a rigid linker to maintain structural and functional integrity. Secondary and tertiary structure predictions were performed using online servers of GOR-IV and I-TASSER. Physicochemical properties and solubility were analyzed using ProtParam and Protein-Sol. Validation and quality assessment of the fusion protein were confirmed through Rampage and ERRAT2. Finally, the fusion protein was docked with 2 receptors (VEGFR and Cadherin) and docked complexes were simulated on GROMACS. The Leptulipin-p28 fusion protein exhibited a stable structure exhibiting a high quality score of 92 on ERRAT and Ramachandran plot analysis highlighting 76.3% of residues in the favorable region. Docking studies with VEGFR and Cadherin receptors followed by 100 ns simulations on GROMACS showed stable complex formation. Molecular dynamics simulations confirmed the stability and robust interaction of the fusion protein-receptor complexes over time. The computational analysis indicates that the Leptulipin-p28 fusion protein holds promise as a multitarget therapeutic agent in breast cancer. The current findings warrant further investigation through in vitro and in vivo studies to validate the current outcomes.

2023-10-13·ACS Pharmacology & Translational Science

Novel Inhibitor of Mixed-Lineage Kinase Domain-Like Protein: The Antifibrotic Effects of a Necroptosis Antagonist

Article

作者: Bae, Sang Hyun ; Kwon, Ye-Mi ; Park, Sunyou ; Jun, Dae Won ; Lee, Jung Yeol ; Choi, Myeong A. ; Kim, Hye Young ; Hong, Eunmi ; Lee, Seung Min ; Lee, Ju Yeon ; Lee, A. Hyeon ; Park, Gye Ryeol ; Lee, Ji Hoon ; Oh, Ju Hee ; Park, Jin-wan

The pseudokinase mixed-lineage kinase domain-like protein plays a crucial role in programmed cell death via necroptosis. We developed a novel mixed-lineage kinase domain-like inhibitor, P28, which demonstrated potent necroptosis inhibition and antifibrotic effects. P28 treatment directly inhibited mixed-lineage kinase domain-like phosphorylation and oligomerization after necroptosis induction, inhibited immune cell death after necroptosis, and reduced the expression of adhesion molecules. Additionally, P28 treatment reduced the level of activation of hepatic stellate cells and the expression of hepatic fibrosis markers induced by necroptosis stimulation. Unlike the necrosulfonamide treatment, the P28 treatment did not induce cytotoxicity. Finally, the cysteine covalent bonding of P28 was confirmed by liquid chromatography-tandem mass spectrometry.

2023-07-01·Molecular Cell

Glucose-induced CRL4COP1-p53 axis amplifies glycometabolism to drive tumorigenesis

Article

作者: Chen, Xing ; Huang, Niu ; Wang, Fengchao ; Zhang, Xiaozhe ; Zhao, Li ; Chen, Hao ; Luo, Yifan ; Su, Yang ; Xiao, Yihang ; Chow, Billy Kwok Chong ; Rao, Feng ; Wu, Mingxuan ; Wei, Xiayun ; Jin, Wenfei ; Zhang, Hongyun ; Fu, Qiuyu ; Nie, Siyue ; Zhang, Peitao ; Ren, Yan ; Wang, Huifang ; Pu, Weijie ; Hao, Yi ; Lin, Hong ; Zhang, Keren

The diabetes-cancer association remains underexplained. Here, we describe a glucose-signaling axis that reinforces glucose uptake and glycolysis to consolidate the Warburg effect and overcome tumor suppression. Specifically, glucose-dependent CK2 O-GlcNAcylation impedes its phosphorylation of CSN2, a modification required for the deneddylase CSN to sequester Cullin RING ligase 4 (CRL4). Glucose, therefore, elicits CSN-CRL4 dissociation to assemble the CRL4^COP1 E3 ligase, which targets p53 to derepress glycolytic enzymes. A genetic or pharmacologic disruption of the O-GlcNAc-CK2-CSN2-CRL4^COP1 axis abrogates glucose-induced p53 degradation and cancer cell proliferation. Diet-induced overnutrition upregulates the CRL4^COP1-p53 axis to promote PyMT-induced mammary tumorigenesis in wild type but not in mammary-gland-specific p53 knockout mice. These effects of overnutrition are reversed by P28, an investigational peptide inhibitor of COP1-p53 interaction. Thus, glycometabolism self-amplifies via a glucose-induced post-translational modification cascade culminating in CRL4^COP1-mediated p53 degradation. Such mutation-independent p53 checkpoint bypass may represent the carcinogenic origin and targetable vulnerability of hyperglycemia-driven cancer.

100 项与 Azurin-p28 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
脉络丛肿瘤	药物发现	美国	National Cancer Institute	2013-08-01
神经胶质肉瘤	药物发现	美国	National Cancer Institute	2013-08-01
髓母细胞瘤	药物发现	美国	National Cancer Institute	2013-08-01
少突神经胶质瘤	药物发现	美国	National Cancer Institute	2013-08-01
实体瘤	药物发现	美国	CDG Therapeutics, Inc.	2009-04-01
实体瘤	药物发现	美国	Dr. Tapas K. Das Gupta	2009-04-01
脑癌	药物发现	-	National Cancer Institute	-
脑癌	药物发现	-	University of Illinois	-
脑癌	药物发现	-	CDG Therapeutics, Inc.	-
中枢神经系统肿瘤	药物发现	美国	-	-