From magic bullets to designed multiple ligands

Morphy, Richard; Kay, Corinne; Rankovic, Zoran

doi:10.1016/s1359-6446(04)03163-0

Cited by 673 publications

(510 citation statements)

References 49 publications

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“…Extensive research over the last half century has made clear that most chronic illnesses can only be cured by multitargeted, as opposed to mono-targeted, therapy [204][205][206] and that promiscuous targeting of a disease cell's multiple bypass mechanisms is a therapeutic virtue [207]. Consequently, agents that can modulate multiple cellular targets are now attractive objects of research.…”

Section: Discussionmentioning

confidence: 99%

Curcumin as “Curecumin”: From kitchen to clinic

Goel

Kunnumakkara

Aggarwal

2008

Biochemical Pharmacology

1,919

1,290

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Section: Discussionmentioning

confidence: 99%

Curcumin as “Curecumin”: From kitchen to clinic

Goel

Kunnumakkara

Aggarwal

2008

Biochemical Pharmacology

1,919

1,290

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“…Depression is one of these multi-target diseases, and various hypothesis or protein factors participate in its pathogenesis, such as monoaminergic hypothesis, HPA axis hypothesis, BDNF, CREB and ERK signaling pathways. It is suggested that a balanced modulation of several targets can offer a better therapeutic effect with less side effects compared to a single selective ligand, significantly in the treatment of chronic and complex diseases (Morphy et al, 2004). In recent years, the development of new drugs aimed at a single molecular target has showed a down trend (Firman et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity

Gao

et al. 2017

Journal of Ethnopharmacology

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Ethnopharmacological relevance: There are many plants of genus Piper which have been reported to induce antidepressant-like effects, Piper sarmentosum (PS) is one of them. PS is a Chinese herbal medicine and a traditional edible vegetable. Materials and Methods:In the present study, the antidepressant-like effects of PS extracts and the ethyl acetate fraction of PS extracts (PSY) were assessed using the open field test (OFT), forced swimming test (FST), and tail suspension test (TST) in mice. Furthermore, we applied a 4 consecutive weeks of chronic unpredictable mild stress (CUMS) as a model of depression in rats, followed by a sucrose preference test. Then we examined the possible mechanisms of this action.The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the serum corticosterone (CORT) concentrations, and the protein expression levels of brain-derived neurotrophic factor (BDNF), the phosphorylated form CREB and ERK1/2 were detected by qRT-PCR or Western blot. Results:The results showed that PS extracts (100, 200 mg/kg) and PSY (12.5, 25, 50 mg/kg) treatment produced antidepressant-like effects in mice similar to fluoxetine (20 mg/kg), indicated by the reduced immobility time in the FST and TST, while both had no influence on the locomotor activity in the OFT. PSY treatment significantly increased sucrose preference and reduced serum CORT levels in CUMS rats. Moreover, PSY up-regulated BDNF protein levels, and increased CREB and ERK phosphorylation levels in the hippocampus on CUMS rats. Conclusions:These findings suggest that the antidepressant-like effects of PS extracts and PSY are mediated, at least in part, by modulating HPA axis, BDNF, CREB and ERK phosphorylation and expression in the hippocampus.

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“…[1][2][3][4] There has already been a move by some companies in the pharmaceutical industry to combine two compounds into one formulation, an expansion of the earlier concept inherent in polypharmacy (i.e., administering two or more drugs as separate medicines). Examples include the combination of a ␤-adrenergic agonist salmeterol with a steroid fluticasone (Advair, GlaxoSmithKline, London, UK) in the treatment of asthma or combining the cholesterol absorption inhibitor ezetimibe (Zetia, Merck & Co., Inc., NJ) with the HMG-CoA reductase enzyme inhibitor simvastatin (Zocor, Merck & Co., Inc.) to render Vytorin (Merck & Co., Inc./Schering-Plough Corporation, NJ).…”

Section: Introductionmentioning

confidence: 99%

“…Although none of these designed drugs have reached the market yet, recent literature suggests this approach to be very promising. 3,4 One question for the medicinal chemist becomes "where to start?" In a review by Morphy and Rankovic, 3,4 the authors describe mechanisms of designing multifunctional drugs.…”

Section: Introductionmentioning

confidence: 99%

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Polycyclic Compounds: Ideal Drug Scaffolds for the Design of Multiple Mechanism Drugs?

Schyf

Geldenhuys

2009

Neurotherapeutics

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Summary:Recently there has been a resurging interest in developing multi-functional drugs to treat diseases with complex pathological mechanisms. Such drug molecules simultaneously target multiple etiologies that have been found to be important modulators in specific diseases. This approach has significant promise and may be more effective than using one compound specific for one drug target or, by a polypharmaceutical approach, using a cocktail of two or more drugs. Polycyclic ring structures are useful as starting scaffolds in medicinal chemistry programs to develop multi-functional drugs, and may also be useful moieties added to existing structures to improve the pharmacokinetic properties of drugs currently used in the clinic or under development. This review attempts to provide a synopsis of current published research to exemplify the use of polycyclic compounds as starting molecules to develop multi-functional drugs.

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From magic bullets to designed multiple ligands

Cited by 673 publications

References 49 publications

Curcumin as “Curecumin”: From kitchen to clinic

Curcumin as “Curecumin”: From kitchen to clinic

Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity

Polycyclic Compounds: Ideal Drug Scaffolds for the Design of Multiple Mechanism Drugs?

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