Recent advances of small-molecule c-Src inhibitors for potential therapeutic utilities.

Bioorg Chem

School of Pharmacy, Key Laboratory of Elemene Class Anticancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China. Electronic address:

Published: October 2023

AI Article Synopsis

  • Proto-oncogene tyrosine-protein kinase Src (c-Src) is a key player in cell processes like division and survival, affecting both healthy and cancerous cells through various signaling pathways.
  • There is a strong link between c-Src and bone-related diseases, such as osteoporosis, because of its role in osteoclasts and inflammation.
  • Recent efforts have led to the development of c-Src inhibitors, with a review highlighting advances in their mechanisms, drug discovery, combination therapies, and ongoing clinical research to inspire further innovation in treatment options.

Article Abstract

Proto-oncogene tyrosine-protein kinase Src, also known as c-Src, belongs to the family of non-receptor tyrosine protein kinases (TKs) called Src kinases. It plays a crucial role in cell division, motility, adhesion, and survival in both normal cells and cancer cells by activating various signaling pathways mediated by multiple cytokines. Additionally, c-Src kinase has been implicated in osteoclasts and bone loss diseases mediated by inflammation and osteoporosis. In recent years, remarkable advancements have been achieved in the development of c-Src inhibitors, with several candidates progressing to the clinical stage. This review focuses on the research progress in several areas, including the mechanism of action, drug discovery, combination therapy, and clinical research. By presenting this information, we aim to provide researchers with convenient access to valuable insights and inspire new ideas to expedite future drug discovery programs.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2023.106934DOI Listing

Publication Analysis

Top Keywords

c-src inhibitors
8
drug discovery
8
advances small-molecule
4
c-src
4
small-molecule c-src
4
inhibitors potential
4
potential therapeutic
4
therapeutic utilities
4
utilities proto-oncogene
4
proto-oncogene tyrosine-protein
4

Similar Publications

Inhibiting de novo lipogenesis identifies a therapeutic vulnerability in therapy-resistant colorectal cancer.

Redox Biol

December 2024

Cell and Tumor Biology, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India. Electronic address:

A significant clinical challenge in patients with colorectal cancer (CRC), which adversely impacts patient survival, is the development of therapy resistance leading to a relapse. Therapy resistance and relapse in CRC is associated with the formation of lipid droplets (LD) by stimulating de novo lipogenesis (DNL). However, the molecular mechanisms underlying the increase in DNL and the susceptibility to DNL-targeted therapies remain unclear.

View Article and Find Full Text PDF

Recent advances of small-molecule c-Src inhibitors for potential therapeutic utilities.

Bioorg Chem

October 2023

School of Pharmacy, Key Laboratory of Elemene Class Anticancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China. Electronic address:

Article Synopsis
  • Proto-oncogene tyrosine-protein kinase Src (c-Src) is a key player in cell processes like division and survival, affecting both healthy and cancerous cells through various signaling pathways.
  • There is a strong link between c-Src and bone-related diseases, such as osteoporosis, because of its role in osteoclasts and inflammation.
  • Recent efforts have led to the development of c-Src inhibitors, with a review highlighting advances in their mechanisms, drug discovery, combination therapies, and ongoing clinical research to inspire further innovation in treatment options.
View Article and Find Full Text PDF

Focal Adhesion Kinase (FAK) and c-Src Dependent Signal Transduction in Cell Adhesion.

Discov Med

October 2024

Laboratory of Human Anatomy and Cell Biology, Faculty of Health Sciences, Tsukuba University of Technology, 305-8521 Tsukuba, Japan.

This review predominantly acquaints the role of focal adhesion kinase (FAK) and cellular-Src (c-Src) in cell adhesion. Cell adhesion is a crucial phenomenon that causes the cells to interact with the extracellular matrix (ECM) or with each other. There are different proteins involved in cell adhesion including cell adhesion molecules (CAMs)/receptors that are present on the cell surface and various cytoplasmic proteins.

View Article and Find Full Text PDF

Structural Basis for Long Residence Time c-Src Antagonist: Insights from Molecular Dynamics Simulations.

Int J Mol Sci

September 2024

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, China.

Article Synopsis
  • c-Src plays a crucial role in various cancer signaling pathways and is a key target for cancer treatment.
  • Research indicates that extending the residence time of drugs can improve their effectiveness, leading to the development of c-Src antagonists with longer residence times.
  • The study utilized molecular dynamics simulations to analyze the binding behavior of different antagonists, identifying a new compound, DFOGS, that enhances binding stability by replacing an unstable amide group, which could lead to better therapeutic outcomes.
View Article and Find Full Text PDF

Applying molecular hybridization to design a new class of pyrazolo[3,4-d]pyrimidines as Src inhibitors active in hepatocellular carcinoma.

Eur J Med Chem

December 2024

Department of Pharmacy, University of Genoa, Viale Benedetto XV 3, 16132, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genova, Largo Rosanna Benzi 10, 16132, Genoa, Italy.

Hepatocellular carcinoma (HCC) is the most common type of liver solid tumor and the second leading cause of cancer-related deaths worldwide. Although new treatment options have been recently approved, the development of tumor resistance and the poor prognosis for advanced HCC make the current standard of care unsatisfying. In this scenario, the non-receptor tyrosine kinase (TK) c-Src emerged as a promising target for developing new anti-HCC agents.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!