Designing multi-targeted agents: An emerging anticancer drug discovery paradigm

Fu, Rong-Geng; Sun, Yuan; Sheng, Wen‐Bing; Liao, Duan‐Fang

doi:10.1016/j.ejmech.2017.05.016

Cited by 172 publications

(105 citation statements)

References 83 publications

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“…12,13 Well-designed DMLs can reduce drug-drug interactions and side effects, and simplify drug pharmacokinetics. 14,15 In search of novel treatment strategies for cancer, we aim to develop dual inhibitors of MET and WNT signaling.…”

Section: Introductionmentioning

confidence: 99%

Towards dual inhibitors of the MET kinase and WNT signaling pathway; design, synthesis and biological evaluation

et al. 2019

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Section: Introductionmentioning

confidence: 99%

Towards dual inhibitors of the MET kinase and WNT signaling pathway; design, synthesis and biological evaluation

et al. 2019

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“…Further, the simplified dosing regimen would greatly aid in enhancing the therapeutic efficacy and exert minimal side effects. 257 These findings clearly indicate that the use of more unspecific agents with ability to modulate different targets simultaneously offer high prospect. 259 Increasing lines of evidence suggest that "natural products" such as isoflavones, indole-3-carbinol, and curcumin inhibited the growth and induced apoptosis of cancer cells effectively by targeting multiple signaling pathways in vitro without causing much toxicity to the normal cells.…”

Section: Multi-targeted Agentsmentioning

confidence: 96%

“…Interestingly, one leading paradigm in drug discovery is to develop regimens with high selectivity to act on individual drug targets. 257,258 With this mono-targeted approach, many novel entities have been designed and further got approval as drugs. 257 However, these drugs had hardly exerted efficacy against cancer as it is a complex disease characterized by diverse molecular and genetic variations.…”

Section: Multi-targeted Agentsmentioning

confidence: 99%

“…In addition, the use of a single agent is generally much more cost-effective than two separate agents. 257,261 Some other important yet added advantages of using a single multi-targeted agent include the avoidance of different bio-availabilities as well as pharmacokinetics and metabolism of each component within the combination regimen. Further, the simplified dosing regimen would greatly aid in enhancing the therapeutic efficacy and exert minimal side effects.…”

Section: Multi-targeted Agentsmentioning

confidence: 99%

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Cancer drug development: The missing links

Kunnumakkara

Bordoloi

Sailo

et al. 2019

Exp Biol Med (Maywood)

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Although better science and technology has been linked with better health care, however, reality is much different. Although America and most of Europe are equipped with most advanced science and technology, paradoxically cancer incidence is highest in the world. This indicates that science and technology alone is not sufficient in treating diseases like cancer. It is also now well recognized that more than 95% of the drugs/compounds that kill either cancer cells in culture or regress the tumors in animals, fail in phase I clinical trials in humans, indicating that most pre-clinical models of cancer are inadequate. In addition, most of the anticancer drugs that are approved by the regulatory agencies such as FDA either has no effect on the overall survival of the cancer patient or may provide an increase in few months in overall survival. This is despite the fact that most targeted therapies that are currently available are highly expensive; thus suggesting the lack of affordability. This review is meant to focus on some of these problems in detail and then provide potential solutions since most cancers are caused by multiple genes, and thus multi-targeted therapies are needed such as natural products which are inexpensive, safe and have been used for thousands of years for both prevention and treatment of cancer. Impact statement The success rate for cancer drugs which enter into phase 1 clinical trials is utterly less. Why the vast majority of drugs fail is not understood but suggests that pre-clinical studies are not adequate for human diseases. In 1975, as per the Tufts Center for the Study of Drug Development, pharmaceutical industries expended 100 million dollars for research and development of the average FDA approved drug. By 2005, this figure had more than quadrupled, to $1.3 billion. In order to recover their high and risky investment cost, pharmaceutical companies charge more for their products. However, there exists no correlation between drug development cost and actual sale of the drug. This high drug development cost could be due to the reason that all patients might not respond to the drug. Hence, a given drug has to be tested in large number of patients to show drug benefits and obtain significant results.

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“…Co‐delivery strategy, where nanomedicine contains multiple therapeutic drugs with similar or different acting mechanisms, is a very promising way to improve the anticancer clinical performance [Sun et al, ; Fu et al, ]. With the decoration of targeting RGD peptide, liposomal doxorubicin can also accommodate additional anticancer drugs to enhance tumor inhibition responses.…”

Section: Liposome Nanoparticlesmentioning

confidence: 99%

RGD Peptide‐Based Target Drug Delivery of Doxorubicin Nanomedicine

Sun

Chen

Liu

et al. 2017

Drug Development Research

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101

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Preclinical Research Doxorubicin (DOX) is commonly used for the treatment of breast cancer and lymphoma. However, its clinical use has been severely limited due to cardiotoxicity, requiring the development of safer and more efficient pharmaceutical formulations of DOX. Advances in nanotechnology have provided new ways to administer chemotherapeutic drugs like DOX are conveyed into the body and to tumor sites. These Nanotechnology approaches have aided in the selective accumulation of DOX into tumor sites via the enhanced permeability and retention. However, the absence of active targeting ligands still hinders the effective delivery of DOX. Among all active targeting ligands developed to date, RGD peptide (Arginylglycylaspartic acid) occupies a unique position owing to its inherent safety, biocompatibility, and targeting ability. Accordingly, modification of DOX with RGD ligand is anticipated to improve transport of DOX into tumor cells. In this review, we discuss using RGD peptide for improving the therapeutic efficacy of DOX nanomedicine. Drug Dev Res 78 : 283–291, 2017. © 2017 Wiley Periodicals, Inc.

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Designing multi-targeted agents: An emerging anticancer drug discovery paradigm

Cited by 172 publications

References 83 publications

Towards dual inhibitors of the MET kinase and WNT signaling pathway; design, synthesis and biological evaluation

Towards dual inhibitors of the MET kinase and WNT signaling pathway; design, synthesis and biological evaluation

Cancer drug development: The missing links

RGD Peptide‐Based Target Drug Delivery of Doxorubicin Nanomedicine

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