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

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100 项与 Azurin-p28 相关的转化医学

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100 项与 Azurin-p28 相关的专利（医药）

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项与 Azurin-p28 相关的文献（医药）

2024-11-05·Toxicology Research

Design and computational analysis of a novel Azurin-BR2 chimeric protein against breast cancer

Article

作者: Bashir, Hamid ; Alanzi, Abdullah R ; Ansari, Mushtaq Ahmad ; Rehman, Hafiz Muhammad ; Chaudry, Afeefa ; Hina, Syeda Mahlaqa ; Nadeem, Tariq ; Kafait, Iram ; Yousaf, Numan ; Khalid, Sania

AbstractCancer is one of most lethal diseases worldwide. Chemotherapeutics and surgeries are among the treatment facilities available for curing cancer. However due to their negative impact on normal cells and drug resistance development, new treatment strategies have yet to be developed. Some microbial products exhibit therapeutic potential for treating cancer. Pseudomonas aeruginosa Azurins have shown anticancer effects against breast cancer without affecting normal cells. To enhance its cytotoxic effect and targeted delivery, we fused Azurin with a cell-penetrating peptide (BR2) through a rigid linker and evaluated its anticancer potential via in silico analysis. The prediction of the secondary and the tertiary structures and analysis of physiochemical properties of chimeric proteins were computationally performed. The Azurin-BR2 chimeric protein has a basic nature with a molecular weight of 16.8 kDa. The quality indices and validation of chimeric proteins were performed with ERRAT2 and Ramachandran plot values, respectively. The quality index of the chimeric protein was predicted to be 81% to 84.6%, and residues residing in the most favoured region were identified. The HDOCK bioinformatics tool was used for docking a chimeric protein with a cancer suppressor protein p53. The results of the current study support that an Azurin-BR2 fusion protein has a high binding affinity for p53 can induce apoptosis in cancerous cells, and can be used in tumor-targeting therapy.

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.

100 项与 Azurin-p28 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
实体瘤	临床1期	美国	CDG Therapeutics, Inc.	2009-04-01
实体瘤	临床1期	美国	Dr. Tapas K. Das Gupta	2009-04-01
脑癌	临床1期	-	CDG Therapeutics, Inc.	-
脑癌	临床1期	-	National Cancer Institute	-
脑癌	临床1期	-	University of Illinois	-
中枢神经系统肿瘤	临床1期	美国	-	-
HIV感染	临床1期	美国	-	-
肿瘤	临床前	美国	Southern Research Institute	2008-05-01