Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021

Wu, Qing; Qian, Wei; Sun, Xiaoli; Jiang, Shaojie

doi:10.1186/s13045-022-01362-9

Cited by 81 publications

(37 citation statements)

References 857 publications

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“…However, in the last decades, many TI agents have entered clinical trials and shown promising anticancer activities and some of these agents were approved to be used for certain kinds of serious cancers. Table 1 shows a list of drugs in clinical developments beside approved drugs that targeted tubulin as an anticancer agent [ 134 ].…”

Section: Approved and Promising Antimitotic Agentsmentioning

confidence: 99%

Recent Advances of Tubulin Inhibitors Targeting the Colchicine Binding Site for Cancer Therapy

Hawash

2022

Biomolecules

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Cancer accounts for numerous deaths each year, and it is one of the most common causes of death worldwide, despite many breakthroughs in the discovery of novel anticancer candidates. Each new year the FDA approves the use of new drugs for cancer treatments. In the last years, the biological targets of anticancer agents have started to be clearer and one of these main targets is tubulin protein; this protein plays an essential role in cell division, as well as in intracellular transportation. The inhibition of microtubule formation by targeting tubulin protein induces cell death by apoptosis. In the last years, numerous novel structures were designed and synthesized to target tubulin, and this can be achieved by inhibiting the polymerization or depolymerization of the microtubules. In this review article, recent novel compounds that have antiproliferation activities against a panel of cancer cell lines that target tubulin are explored in detail. This review article emphasizes the recent developments of tubulin inhibitors, with insights into their antiproliferative and anti-tubulin activities. A full literature review shows that tubulin inhibitors are associated with properties in the inhibition of cancer cell line viability, inducing apoptosis, and good binding interaction with the colchicine binding site of tubulin. Furthermore, some drugs, such as cabazitaxel and fosbretabulin, have been approved by FDA in the last three years as tubulin inhibitors. The design and development of efficient tubulin inhibitors is progressively becoming a credible solution in treating many species of cancers.

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Section: Approved and Promising Antimitotic Agentsmentioning

confidence: 99%

Recent Advances of Tubulin Inhibitors Targeting the Colchicine Binding Site for Cancer Therapy

Hawash

2022

Biomolecules

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“…To overcome functional redundancy and to develop a tunable inhibition strategy, we performed a target based chemical screen for small molecules that inhibit type II metacaspases. Small molecule inhibitors are often used as a means to inhibit therapeutic targets in a clinical setting, including proteases (Wu et al, 2022), but were also successfully applied to unravel biological mechanisms in plants, such as perception of the plant hormones ABA and brassinosteroid, membrane trafficking and primary metabolism (De Rybel et al, 2009;Kim et al, 2011;Kerchev et al, 2015;Dejonghe & Russinova, 2017;Rohzon et al, 2019;Vaidya et al, 2019Vaidya et al, , 2021. In contrast, few examples exist in the literature of small molecules that modulate plant protease activity in vivo.…”

Section: A New Group Of Small Molecules For In Vivo Inhibition Of Met...mentioning

confidence: 99%

Structure-function analysis of a calcium-independent metacaspase reveals a novel proteolytic pathway for lateral root emergence

Stael

Sabljić

Audenaert

et al. 2023

Preprint

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Metacaspases are part of an evolutionarily broad family of multifunctional cysteine proteases, involved in disease and normal development. Despite the extensive study of metacaspases in the two decades since their discovery, the structure-function relationship of metacaspases remains poorly understood. Furthermore, previous studies on their function have been thwarted by the redundancy in gene copy number and potential phenotypic suppression of genetic mutations, especially in plants. Here, we have solved the X-ray crystal structure of an Arabidopsis thaliana type II metacaspase (AtMCA-IIf) that belongs to a particular sub-group that does not require calcium ions for activation. Compared to crystal structures of other metacaspases and caspases, the AtMCA-IIf active site is structurally similar and poses a conundrum for the catalytic mechanism of the cysteine-histidine dyad. To study metacaspase activity in plants, we developed an in vitro chemical screen to identify small molecule metacaspase inhibitors. Several hits with a minimal thioxodihydropyrimidine-dione (TDP) structure were identified, some being specific inhibitors of AtMCA-IIf. We provide a mechanistic basis for inhibition by the TDP-containing compounds through molecular docking onto the AtMCA-IIf crystal structure. Finally, a TDP-containing compound (TDP6) was effective at inhibiting lateral root emergence in vivo, likely through the inhibition of metacaspases that are specifically expressed in the endodermal cells overlaying developing lateral root primordia. In the future, the small compound inhibitors and crystal structure of AtMCA-IIf can be used to study metacaspases in various other species, such as important human pathogens including those causing neglected diseases.

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“…Although a significant number of gene variants specific anti-tumor drugs have been approved by the FDA, the percentage of personalized medicines is less than 10% of all the FDA approved drugs [142]. The development of personalized medicines still confronts some challenges: 1) Interpretation of genetic variations thousands of mutant genes are scattered throughout the genome of cancer cells, and there are hundreds of different mutant genes associated with cancer [143].…”

Section: The Future Challenges Of Personalized Therapymentioning

confidence: 99%

Review of Personalized Medicine and Pharmacogenomics of Anti-Cancer Compounds and Natural Products

Zhou¹,

Peng²,

Wang³

et al. 2023

Preprint

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In recent years, the FDA has approved numerous antitumor drugs that are mutation-based for clinical use. These drugs have improved the precision of treatment and reduced adverse effects and side effects. Personalized therapy is a prominent and hot topic of current medicine and also represents the future direction of development. With the continuous advancements in gene sequencing and high-throughput screening, research and development strategies for personalized clinical drugs have developed rapidly. This review elaborated the recent personalized treatment strategies, which include artificial intelligence, multi-omics analysis, chemical proteomics, and computation aided drug design. These technologies rely on the molecular classification of diseases, the global signaling network within organisms, and new models for all targets, which significantly support the development of personalized medicine. Meanwhile, we summarized chemical drugs such as lorlatinib, osimertinib, and other natural products that deliver personalized therapeutic effects based on genetic mutations. This review also highlights potential challenges in interpreting genetic mutations and combining drugs, while providing new ideas for the development of personalized medicine and pharmacogenomics in cancer study.

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Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021

Cited by 81 publications

References 857 publications

Recent Advances of Tubulin Inhibitors Targeting the Colchicine Binding Site for Cancer Therapy

Recent Advances of Tubulin Inhibitors Targeting the Colchicine Binding Site for Cancer Therapy

Structure-function analysis of a calcium-independent metacaspase reveals a novel proteolytic pathway for lateral root emergence

Review of Personalized Medicine and Pharmacogenomics of Anti-Cancer Compounds and Natural Products

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