The efficiency of multi-target drugs: the network approach might help drug design

Csermely, Péter; Ágoston, Vilmos; Pongor, Sándor

doi:10.1016/j.tips.2005.02.007

Cited by 719 publications

(553 citation statements)

References 34 publications

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“…Multitarget therapeutic strategy can be used to inhibit two or more enzymes, act on an enzyme and a receptor, or affect an ion channel and a transporter 17 . Using this strategy, a single molecule hits multiple targets, which participate in pathways implicated to a given disease 18 . Therefore, it is evident that the treatment of AD could benefit from the use of multipotent drugs that present free radical scavenging, anti-inflammatory and AChE inhibitory activity.…”

Section: Introductionmentioning

confidence: 99%

Simple chalcones and bis-chalcones ethers as possible pleiotropic agents

Liargkova

Hadjipavlou‐Litina

Koukoulitsa

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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The synthesis, the antioxidative properties and the lipoxygenase (LOX) and acetylcholinesterase (AChE) inhibition of a number of 4-hydroxy-chalcones diversely substituted as well as of a series of bis-chalcones ether derivatives are reported. The chalcones derivatives were readily produced using a Claisen-Schmidt condensation in a ultra sound bath in good yields. The structures of the synthesized compounds were confirmed by spectral and elemental analysis. Their lipophilicity is experimentally determined by reversed-phase thin-layer chromatography method. Most of them are potent in vitro inhibitors of lipid peroxidation and of LOX. Compounds b2 and b3 were found to be the most potent LOX and AChE inhibitors among the tested derivatives with a significant anti-lipid peroxidation profile. The results led us to propose these enone derivatives as new multifunctional compounds against Alzheimer's disease. The results are discussed in terms of structural and physicochemical characteristics of the compounds. Moreover, the pharmacokinetic profile of these compounds was investigated using computational methods.

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Section: Introductionmentioning

confidence: 99%

Simple chalcones and bis-chalcones ethers as possible pleiotropic agents

Liargkova

Hadjipavlou‐Litina

Koukoulitsa

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…They applied network efficiency measure [38] to compute pathway cross-talk inhibition (PCI). PCI is the reduction of network efficiency after a pharmacologic intervention.…”

Section: Systems Biology Based Methodsmentioning

confidence: 99%

In-Silico Methodologies for Cancer Multidrug Optimization

Hasan¹,

Eldin

Khedr

et al. 2018

IJCT

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Drug combinations is considered as an effective strategy designed to control complex diseases like cancer. Combinations of drugs can effectively decrease side effects and enhance adaptive resistance. Therefore, increasing the likelihood of defeating complex diseases in a synergistic way. This is due to overcoming factors such as off-target activities, network robustness, bypass mechanisms, cross-talk across compensatory escape pathways and the mutational heterogeneity which results in alterations within multiple molecular pathways. The plurality of effective drug combinations used in clinic were found out through experience. The molecular mechanisms underlying these drug combinations are often not clear. It is not easy to suggest new drug combinations. Computational approaches are proposed to reduce the search space for defining the most promising combinations and prioritizing their experimental evaluation. In this paper, we review methods, techniques and hypotheses developed for in silico methodologies for drug combination discovery in cancer and discuss the limitations and challenges of these methods.

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“…Some models indeed indicate that partial inhibition of a few targets is more effective than full inhibition of a single target (Csermely et al 2005). Targeting NB cells and tumours as a system instead of targeting single molecules might allow the discovery of a novel class of multi-target drugs, which would have fewer adverse effects and less toxicity.…”

Section: Future Prospectsmentioning

confidence: 99%

Neuroblastoma therapy: what is in the pipeline?

Veríssimo¹,

Molenaar²,

Fitzsimons³

et al. 2011

Endocrine-Related Cancer

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Despite the expansion of knowledge about neuroblastoma (NB) in recent years, the therapeutic outcome for children with a high-risk NB has not significantly improved. Therefore, more effective therapies are needed. This might be achieved by aiming future efforts at recently proposed but not yet developed targets for NB therapy. In this review, we discuss the recently proposed molecular targets that are in clinical trials and, in particular, those that are not yet explored in the clinic. We focus on the selection of these molecular targets for which promising in vitro and in vivo results have been obtained by silencing/inhibiting them. In addition, these selected targets are involved at least in one of the NB tumorigenic processes: proliferation, anti-apoptosis, angiogenesis and/or metastasis. In particular, we will review a recently proposed target, the microtubule-associated protein (MAP) encoded by doublecortin-like kinase gene (DCLK1). DCLK1-derived MAPs are crucial for proliferation and survival of neuroblasts and are highly expressed not only in NB but also in other tumours such as gliomas. Additionally, we will discuss neuropeptide Y, its Y2 receptor and cathepsin L as examples of targets to decrease angiogenesis and metastasis of NB. Furthermore, we will review the micro-RNAs that have been proposed as therapeutic targets for NB. Detailed investigation of these not yet developed targets as well as exploration of multi-target approaches might be the key to a more effective NB therapy, i.e. increasing specificity, reducing toxicity and avoiding long-term side effects.

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The efficiency of multi-target drugs: the network approach might help drug design

Cited by 719 publications

References 34 publications

Simple chalcones and bis-chalcones ethers as possible pleiotropic agents

Simple chalcones and bis-chalcones ethers as possible pleiotropic agents

In-Silico Methodologies for Cancer Multidrug Optimization

Neuroblastoma therapy: what is in the pipeline?

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