scholarly journals Focal adhesion kinase inhibitors, a heavy punch to cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yueling Wu ◽  
Ning Li ◽  
Chengfeng Ye ◽  
Xingmei Jiang ◽  
Hui Luo ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Kinase Inhibitors ◽  
Early Stage ◽  
Perspective View ◽  
Combination Strategy ◽  
Cancer Cell Growth ◽  
Cancer Types ◽  
Chemotherapy Strategy

AbstractKinases are the ideal druggable targets for diseases and especially were highlighted on cancer therapy. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase and its aberrant signaling extensively implicates in the progression of most cancer types, involving in cancer cell growth, adhesion, migration, and tumor microenvironment (TME) remodeling. FAK is commonly overexpressed and activated in a variety of cancers and plays as a targetable kinase in cancer therapy. FAK inhibitors already exhibited promising performance in preclinical and early-stage clinical trials. Moreover, substantial evidence has implied that targeting FAK is more effective in combination strategy, thereby reversing the failure of chemotherapies or targeted therapies in solid tumors. In the current review, we summarized the drug development progress, chemotherapy strategy, and perspective view for FAK inhibitors.

scholarly journals Qualitative Prediction of Ligand Dissociation Kinetics from Focal Adhesion Kinase Using Steered Molecular Dynamics

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 74
Author(s):  
Justin Spiriti ◽  
Chung F. Wong
Keyword(s):  
Molecular Dynamics ◽  
Drug Discovery ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Early Stage ◽  
Steered Molecular Dynamics ◽  
Drug Binding ◽  
Binding Kinetics ◽  
Dissociation Kinetics ◽  
Binding Characteristics

Most early-stage drug discovery projects focus on equilibrium binding affinity to the target alongside selectivity and other pharmaceutical properties. Since many approved drugs have nonequilibrium binding characteristics, there has been increasing interest in optimizing binding kinetics early in the drug discovery process. As focal adhesion kinase (FAK) is an important drug target, we examine whether steered molecular dynamics (SMD) can be useful for identifying drug candidates with the desired drug-binding kinetics. In simulating the dissociation of 14 ligands from FAK, we find an empirical power–law relationship between the simulated time needed for ligand unbinding and the experimental rate constant for dissociation, with a strong correlation depending on the SMD force used. To improve predictions, we further develop regression models connecting experimental dissociation rate with various structural and energetic quantities derived from the simulations. These models can be used to predict dissociation rates from FAK for related compounds.

Design, Synthesis, and Evaluation of Novel Imidazo[1,2-a][1,3,5]triazines and Their Derivatives as Focal Adhesion Kinase Inhibitors with Antitumor Activity

2014 ◽  
Vol 58 (1) ◽  
pp. 237-251 ◽  
Author(s):  
Pascal Dao ◽  
Nikaia Smith ◽  
Céline Tomkiewicz-Raulet ◽  
Expédite Yen-Pon ◽  
Marta Camacho-Artacho ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Kinase Inhibitors ◽  
Design Synthesis

Focal adhesion kinase inhibitors in the treatment of metastatic cancer: a patent review

2014 ◽  
Vol 24 (10) ◽  
pp. 1077-1100 ◽  
Author(s):  
Ekambaram Shanthi ◽  
Mudeenahally H Krishna ◽  
Gubbi M Arunesh ◽  
K Venkateswara Reddy ◽  
Jegatheesan Sooriya Kumar ◽  
...  
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Kinase Inhibitors ◽  
Metastatic Cancer ◽  
Patent Review

Fragment-Based Discovery of New Highly Substituted 1H-Pyrrolo[2,3-b]- and 3H-Imidazolo[4,5-b]-Pyridines as Focal Adhesion Kinase Inhibitors

2013 ◽  
Vol 56 (3) ◽  
pp. 1160-1170 ◽  
Author(s):  
Timo Heinrich ◽  
Jeyaprakashnarayanan Seenisamy ◽  
Lourdusamy Emmanuvel ◽  
Santosh S. Kulkarni ◽  
Jörg Bomke ◽  
...  
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Kinase Inhibitors

Integrins as A New Target for Cancer Treatment

2019 ◽  
Vol 19 (5) ◽  
pp. 580-586 ◽  
Author(s):  
Izabela Łasiñska ◽  
Jacek Mackiewicz
Keyword(s):  
Monoclonal Antibodies ◽  
Cancer Therapy ◽  
Cancer Treatment ◽  
Kinase Inhibitors ◽  
Cancer Cell Death ◽  
Intracellular Signals ◽  
Different Types ◽  
Lung Cancer Therapy ◽  
Cancer Types ◽  
Melanoma Therapy

:Despite the great progress in the development of targeted therapies for different types of cancer utilizing monoclonal antibodies (e.g., cetuximab for colorectal cancer and head and neck cancer therapy), kinase inhibitors (e.g., sorafenib for kidney cancer and gastrointestinal stromal tumours therapy), and immunomodulatory treatments (e.g., nivolumab and pembrolizumab for melanoma therapy and lung cancer therapy), there is still a need to search for new, more effective treatments.:Integrins are responsible for intercellular adhesion and interaction with the cellular matrix. The function of integrins is related to the transduction of intracellular signals associated with adhesion, migration, cell proliferation, differentiation, and apoptosis. Molecules targeting integrins that lead to cancer cell death have been developed. The most advanced molecules studied in clinical trials are abituzumab, intetumumab and cilengitide. There are different groups of anti-integrin drugs: monoclonal antibodies (e.g., abituzumab) and other such as cilengitide, E7820 and MK-0429. These drugs have been evaluated in various cancer types. However, they have shown modest efficacy, and none of them have yet been approved for cancer treatment. Studies have shown that patient selection using biomarkers might improve the efficacy of anti-integrin cancer treatment. Many preclinical models have demonstrated promising results using integrin visualization for cancer detection and treatment efficacy monitoring; however, these strategies require further evaluation in humans.

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