![]() Currently, a large number of protein kinase inhibitors have been reported. ![]() Protein kinases are the most widely studied tumor therapeutic targets. Dysregulation of protein kinases is linked to various diseases, particularly cancer. 6 According to the substrate residues, protein kinases can be classified as tyrosine kinases (including both receptor and non-receptor tyrosine kinases), serine/threonine kinases, and tyrosine kinase-like enzymes. 5 The human kinome comprises ~535 protein kinases. ![]() It has an important role in cell growth, proliferation, and differentiation (Fig. Protein kinase is a kind of enzyme that catalyzes the transfer of γ-phosphate group from ATP to protein residues containing hydroxyl groups. It is undeniable that small-molecule targeted anti-cancer drugs still face many challenges such as low response rate and drug resistance. The targets of these drugs cover a large scope including kinases, epigenetic regulatory proteins, DNA damage repair enzymes, and proteasomes. Figure 1 summarizes the small-molecule anti-cancer drugs approved by the US FDA and National Medical Products Administration (NMPA) of China since 2001. To date, there are a total of 89 anti-cancer small molecules approved in the United States and China. Despite challenged by macromolecule drugs represented by monoclonal antibodies in recent years, small-molecule targeted drugs still gain great development. 3, 4 Compared with macromolecule drugs, small-molecule targeted drugs have advantages in some aspects such as the pharmacokinetic (PK) properties, costs, patient compliance, and drug storage and transportation (Supplementary Table S1). Targeted drugs can be roughly classified into two categories: small molecules and macromolecules (e.g., monoclonal antibodies, polypeptides, antibody–drug conjugates, and nucleic acids). In the past 20 years, there has been a significant increase in FDA-approved targeted drugs for cancer treatment. Encouraged by the approval of the first small-molecule tyrosine kinase inhibitor (TKI) imatinib for clinical use by the US Food and Drug Administration (FDA) in 2001, 2 targeted drugs have rapidly developed and entered a golden period of development. 1 Compared with traditional chemotherapy drugs, targeted drugs can specifically target cancer cells but spare normal cells, hence having high potency and low toxicity. Over the past two decades, there has been a tremendous shift in cancer treatment, from broad-spectrum cytotoxic drugs to targeted drugs. The biggest characteristic of chemotherapy is the inability to distinguish between cancer cells and normal cells, resulting in significant toxicity and side effects. For a long time, chemotherapy, which is a method of killing tumor cells and/or inhibiting the growth and proliferation of tumor cells by chemical drugs, was the only approach to cancer drug therapy. We present all the approved drugs as well as important drug candidates in clinical trials for each target, discuss the current challenges, and provide insights and perspectives for the research and development of anti-cancer drugs.ĭrug treatment together with surgical operation, radiotherapy and biotherapy constitute the main approaches to cancer treatment. To better promote the development of targeted anti-cancer drugs, we conducted a comprehensive review of small-molecule targeted anti-cancer drugs according to the target classification. Despite great progress, small-molecule targeted anti-cancer drugs still face many challenges, such as a low response rate and drug resistance. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments.
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