Results 61 to 70 of about 644,957 (254)

Beyond Nature's Blueprint: Macrocyclic Peptides Containing Unnatural Amino Acids in Therapeutic Development

Angewandte Chemie, EarlyView.
Strategic incorporation of unnatural amino acids transforms macrocyclic peptides into drug‐like molecules capable of engaging challenging targets. These building blocks enhance stability, permeability, and bioavailability, accelerating the development of next‐generation peptide therapeutics.
Krishna K. Sharma, Komal Sharma, Anku Sharma, Kamya Rao, Rahul Jain, Brett VanVeller   +5 more
wiley   +2 more sources

Insights into the Interaction Mechanisms of Peptide and Non-Peptide Inhibitors with MDM2 Using Gaussian-Accelerated Molecular Dynamics Simulations and Deep Learning

Molecules
Inhibiting MDM2-p53 interaction is considered an efficient mode of cancer treatment. In our current study, Gaussian-accelerated molecular dynamics (GaMD), deep learning (DL), and binding free energy calculations were combined together to probe the ...
Wanchun Yang, Jian Wang, Lu Zhao, Jianzhong Chen   +3 more
doaj   +1 more source

Synergistic p53 Pathway Activation Through Sono‐Gene Therapy Induced by Ultrasound‐Triggered Theranostic Mesoporous Nanoparticles

Advanced Science, EarlyView.
Schematic representation of ultrasound‐mediated ICG/siCD24@MSN‐LCD from nanostructure to synergistic sono‐gene therapy. This nanoplatform targets ASGPR via the LCD shell, which dissociates to release loaded ICG and siCD24. The core mechanism involves ultrasound‐guided sonodynamic therapy by ICG and CD24 knockdown by siCD24, both activating the p53 axis
Yading Zhao, Lu Guo, Dandan Shi, Xiao Sun, Mengmeng Shang, Song Ning, Shuting Huang, Xiaoxuan Wang, Rui Liu, Yuye Fu, Suyun Li, Jie Li   +11 more
wiley   +1 more source

Backbone Steric Constraints Underlie High Passive Membrane Permeability of N‐Alkyl Peptides

Angewandte Chemie, EarlyView.
Beyond amide hydrogen removal, steric constraints encoded in N/Cα‐dually substituted backbones are uncovered as a key determinant of passive membrane permeability in N‐alkyl peptides. These constraints restrict conformational freedom and sterically limit backbone hydration during membrane permeation.
Ayumi Inayoshi, Mariko Akiba, Marin Yokomine, Masatake Sugita, Koji Umezawa, Yuto Hirota, Yutaka Akiyama, Jumpei Morimoto, Shinsuke Sando   +8 more
wiley   +2 more sources

Targeting Mouse Double Minute 2: Current Concepts in DNA Damage Repair and Therapeutic Approaches in Cancer

Frontiers in Pharmacology, 2020
Defects in DNA damage repair may cause genome instability and cancer development. The tumor suppressor gene p53 regulates cell cycle arrest to allow time for DNA repair.
Wen Li, Xinhao Peng, Xinhao Peng, Jinyi Lang, Jinyi Lang, Chuan Xu   +5 more
doaj   +1 more source

Fibrillarin Resists Cellular Senescence Via SIRT1‐Dependent Nicotinamide Metabolism and Its Inhibition Sensitizes Senolytic Therapy in Esophageal Squamous Cell Carcinoma

Advanced Science, EarlyView.
FBL directly binds to and stabilizes SIRT1 by blocking its ubiquitin‐proteasome degradation, thereby sustaining nicotinamide metabolism and redox homeostasis to counteract cellular senescence in ESCC. Genetic and pharmacological suppression of FBL sensitizes tumor cells to senolytic therapy.
Xing Jin, Hong Liu, Ling Gao, Lei Liu, Ji‐Bin Liu, Xiaoxia Jin, Ming‐Song Wang, Dan Liu, Li Feng, Wen‐Lian Chen   +9 more
wiley   +1 more source

Beyond Simple Mimicry: Next‐Generation Geometric Architectures and Future Paradigms in Small‐Molecule and Macrocyclic Peptidomimetics

Angewandte Chemie, EarlyView.
Peptide‐to‐Small Molecule Paradigm: Peptidomimetics have evolved from simple mimicry toward drug‐like scaffolds supported by increasing clinical successes. This Perspective highlights the geometric design principles—linear repetition, convergent fusion, and cyclization—defining the next‐generation peptidomimetic architectures capable of targeting ...
Jesang Lee, Sumin Son, Jeong Yeon Yoo, Ji Hyae Lee, Meehyun Chun, Seung Bum Park   +5 more
wiley   +2 more sources

MDM2 Protein Inhibitors Therapeutics Clinical Trials & Results

, 2019
MDM2 protein are powerful oncogene which is overexpressed in various cancers, including breast cancer and sarcoma. There are many small molecule drug candidates that are being developed as MDM2 protein inhibitors as monotherapy or combination therapy for
Pharma Proff
core   +1 more source

TRIM28‐Derived Peptide Exerts Anti‐Tumor Roles by Stabilizing Tumor Suppressive BRD7 Protein in Multiple Cancers

Advanced Science, EarlyView.
An α‐helical peptide, TAB12, designed to mimic the TRIM28 binding interface, competitively disrupts the TRIM28‐BRD7 interaction, thereby blocking ubiquitin‐mediated degradation of the tumor suppressor BRD7. This stabilization unleashes potent anti‐tumor effects across multiple tumor types with a favorable safety profile, offering a feasible strategy ...
Qingqing Wei, Changning Xue, Mengna Li, Jianxia Wei, Lemei Zheng, Shipeng Chen, Yijie Wang, Yumei Duan, Yanwei Luo, Wei Xiong, Ming Zhou   +10 more
wiley   +1 more source

Inhibitors of the MDM2-p53 interaction as anticancer drugs

The normal functioning of the important tumor suppressor protein p53 is regulated by its binding to the MDM2 protein. Overexpression of MDM2 in some tumors is responsible for the inactivation of p53. Drugs designed to inhibit the MDM2-p53 protein-protein
Hardcastle IR
core   +5 more sources