Applications of macrocyclic molecules in cancer therapy: Target cancer development or overcome drug resistance
Xiaoling Song,
Yifan Wu,
Xiaojuan Qu
et al.
Abstract:Cancer is a worldwide leading cause of cancer‐related death due to a lack of efficient disease control by drugs. With the increasing unmet needs in cancer treatment, developing novel effective cancer drugs is in great demand. Macrocyclic molecules represent a group of drug molecules with a cyclic skeleton which endows them with unique drug properties such as improved bioavailability, enhanced metabolic stability, increased binding affinity, and favorable pharmacokinetics parameters. The Food and Drug Administr… Show more
“…This is because several drug targets that are crucial for the development of cancer are also involved in the drug resistance for other target proteins. For instance, patients who have drug resistance from EGFR-targeted therapy may benefit from a combination of mTOR inhibitors due to enhanced mTOR signaling [36].…”
Section: Macrocyclic Compounds Targeting Cancer Development and To Ov...mentioning
confidence: 99%
“…Lorlatinib is a small, compact drug with good brain penetration that potently suppresses the growth of resistant malignancies that have relapsed after earlier-generation therapy. In order to overcome resistance to the previous generation of acyclic ALK-specific inhibitor medicines, lorlatinib was licensed (2018) for the treatment of ALK-positive NSCLC [36]. SB1578 and zotiraciclib, two novel JAK2 inhibitors that target the development of cancer, as well as novel inhibitors of ALK, TRK, and EGFR that target the development of drug resistance to targeted therapy, are now in the exploratory stage.…”
Section: Macrocyclic Compounds Targeting Cancer Development and To Ov...mentioning
The profound pharmacological attributes of macrocyclic compounds have spurred their transformation into pharmaceutical drugs. Within conformationally pre-organized ring structures, the macrocycle’s intricate functions and stereochemical complexity contribute to a heightened affinity and selectivity for protein targets. Simultaneously, they maintain sufficient bioavailability to penetrate intracellular locations. As a result, the construction of macrocycles emerges as an optimal strategy for addressing the challenge of “undruggable” targets like cancer. Cancer stands as the second most prevalent and formidable threat to human life, prompting researchers to channel their efforts toward the extraction and synthesis of effective therapeutic drugs designed on macrocyles to combat various types of cancer cells. Many macrocyclic drugs have been licensed by the Food and Drug Administration (FDA) for the treatment of cancer patients. Nonetheless, the significance of these compounds in the production of cancer therapeutics is still undervalued. According to recent research, macrocyclic compounds can be a useful tactic in the fight against drug resistance in the treatment of cancer. This chapter aims to present bits of evidence about the uses of macrocyclic compounds as potential cancer treatments. By providing more innovative approaches to aid cancer patients and society as a whole, this chapter will hopefully stimulate greater interest in the development of macrocyclic medicines for cancer therapy.
“…This is because several drug targets that are crucial for the development of cancer are also involved in the drug resistance for other target proteins. For instance, patients who have drug resistance from EGFR-targeted therapy may benefit from a combination of mTOR inhibitors due to enhanced mTOR signaling [36].…”
Section: Macrocyclic Compounds Targeting Cancer Development and To Ov...mentioning
confidence: 99%
“…Lorlatinib is a small, compact drug with good brain penetration that potently suppresses the growth of resistant malignancies that have relapsed after earlier-generation therapy. In order to overcome resistance to the previous generation of acyclic ALK-specific inhibitor medicines, lorlatinib was licensed (2018) for the treatment of ALK-positive NSCLC [36]. SB1578 and zotiraciclib, two novel JAK2 inhibitors that target the development of cancer, as well as novel inhibitors of ALK, TRK, and EGFR that target the development of drug resistance to targeted therapy, are now in the exploratory stage.…”
Section: Macrocyclic Compounds Targeting Cancer Development and To Ov...mentioning
The profound pharmacological attributes of macrocyclic compounds have spurred their transformation into pharmaceutical drugs. Within conformationally pre-organized ring structures, the macrocycle’s intricate functions and stereochemical complexity contribute to a heightened affinity and selectivity for protein targets. Simultaneously, they maintain sufficient bioavailability to penetrate intracellular locations. As a result, the construction of macrocycles emerges as an optimal strategy for addressing the challenge of “undruggable” targets like cancer. Cancer stands as the second most prevalent and formidable threat to human life, prompting researchers to channel their efforts toward the extraction and synthesis of effective therapeutic drugs designed on macrocyles to combat various types of cancer cells. Many macrocyclic drugs have been licensed by the Food and Drug Administration (FDA) for the treatment of cancer patients. Nonetheless, the significance of these compounds in the production of cancer therapeutics is still undervalued. According to recent research, macrocyclic compounds can be a useful tactic in the fight against drug resistance in the treatment of cancer. This chapter aims to present bits of evidence about the uses of macrocyclic compounds as potential cancer treatments. By providing more innovative approaches to aid cancer patients and society as a whole, this chapter will hopefully stimulate greater interest in the development of macrocyclic medicines for cancer therapy.
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