Computational and Experimental Approaches in Multi-target Pharmacology

Editorial

30 June 2017

Editorial: Computational and Experimental Approaches in Multi-target Pharmacology

Thomas J. Anastasio

4,809 views

13 citations

Editors

Thomas J. Anastasio

University of Illinois at Urbana-Champaign

Impact

Frequency of hydrophobic contacts (green) and hydrogen bonding (orange) between ursolic acid + GluN1a (A), ursolic acid + GluN2B (B), memantine + GluN1a (C), and memantine + GluN2B (D).

Original Research

22 May 2017

Antinociceptive Activity of Borreria verticillata: In vivo and In silico Studies

Rosa H. M. Silva

, 9 more and

João B. S. Garcia

6,011 views

16 citations

Effects of gemcitabine and gemcitabine plus fragments on the viability of SH-SY5Y cells. Apart from fragments 10 and 20, the effects of the fragments were not statistically significant at the P < 0.05 level, n = 3 per experiment.

Original Research

27 March 2017

Enhancing Drug Efficacy and Therapeutic Index through Cheminformatics-Based Selection of Small Molecule Binary Weapons That Improve Transporter-Mediated Targeting: A Cytotoxicity System Based on Gemcitabine

Justine M. Grixti

, 2 more and

Douglas B. Kell

7,790 views

27 citations

Protocatechuic aldehyde prevented cisplatin-induced renal injury and decline of renal function in vivo. (A) PAS staining and score. Results of PAS staining and score of severity indicate that treatment of a set concentrations of PA alleviated tubular necrosis, tubular dilation, and cast formation in cisplatin nephropathy; (B) Serum Creatinine; (C) BUN. Results of serum creatinine and BUN show that treatment of PA restored renal function in cisplatin nephropathy. Data represent the mean ± SEM for 6–8 mice. ∗∗p < 0.01, ∗∗∗p < 0.001 compared to control. ##p < 0.01, ###p < 0.001 compared to model. Cis, cisplatin; PA, protocatechuic aldehyde.

Original Research

06 December 2016

Protocatechuic Aldehyde Attenuates Cisplatin-Induced Acute Kidney Injury by Suppressing Nox-Mediated Oxidative Stress and Renal Inflammation

Li Gao

, 15 more and

Xiao-Ming Meng

5,844 views

80 citations

Distinct dynamics in in physiological, dystonia, and latch-up simulations. (A) Average E5P firing rate vector (FV) similarity vs. average E5P firing rate for individual simulations. (B) E5P MUA Beta oscillation amplitude vs. E5P synchrony for individual simulations. (A,B) [light blue: physiological, purple: dystonia, orange: epileptiform, black: remaining Active simulations, large circles represent simulations shown in (C) and Figure 3]. (C) Pearson correlations between all pairs of E5P FVs. Solid black lines demarcate FVs from example physiological, dystonia, and epileptiform simulations. All FVs used 50 ms intervals, forming 40 FVs per 2 s of simulation.

Original Research

14 June 2016

Multitarget Multiscale Simulation for Pharmacological Treatment of Dystonia in Motor Cortex

Samuel A. Neymotin

, 3 more and

William W. Lytton

4,846 views

33 citations

Two strategies for anti-cancer therapy. (A) Node killing strategy kills sub-clones of cancer cells through chemo-, targeted-, and immuno-therapy. The adaptive evolution of the cancer often leads to drug resistance. The cancer often turns into a more aggressive form. (B) Edge perturbation strategy aims to disturb the cell-cell interactions of the cancer ecosystem. It may have bigger impact on the cancer as a whole. It is less likely for the cancer to evolve into a drug resistance phenotype, as no sub-clone can gain particular evolutionary advantage.

Opinion

24 September 2015

Developing multi-target therapeutics to fine-tune the evolutionary dynamics of the cancer ecosystem

Lei Xie

and

Philip E. Bourne

6,767 views

55 citations

Complex pharmacology of antipsychotics and their major metabolites (forming the active moiety of currently used antipsychotic medication) illustrated by the pKa (−10logKi) against the human receptors, where Ki is the affinity of the drug determined by tracer displacement studies. More peripheral readouts correspond to higher affinities. Data are derived from the standardized PDSP database (http://pdsp.med.unc.edu/indexR.html). It is clear that many antipsychotics have complex pharmacologies leading to non-linear interactions in the human networks. (A) pharmacology of active moiety of aripiprazole, haldoperidol, and olanzapine, (B) pharmacology of risperidone and quetiapine.

Original Research

22 September 2015

Assessing the synergy between cholinomimetics and memantine as augmentation therapy in cognitive impairment in schizophrenia. A virtual human patient trial using quantitative systems pharmacology

Hugo Geerts

, 1 more and

Athan Spiros

4,734 views

30 citations

Perspective

22 September 2015

Multi-target pharmacology: possibilities and limitations of the “skeleton key approach” from a medicinal chemist perspective

Alan Talevi

Multi-target drugs have raised considerable interest in the last decade owing to their advantages in the treatment of complex diseases and health conditions linked to drug resistance issues. Prospective drug repositioning to treat comorbid conditions is an additional, overlooked application of multi-target ligands. While medicinal chemists usually rely on some version of the lock and key paradigm to design novel therapeutics, modern pharmacology recognizes that the mid- and long-term effects of a given drug on a biological system may depend not only on the specific ligand-target recognition events but also on the influence of the repeated administration of a drug on the cell gene signature. The design of multi-target agents usually imposes challenging restrictions on the topology or flexibility of the candidate drugs, which are briefly discussed in the present article. Finally, computational strategies to approach the identification of novel multi-target agents are overviewed.

22,901 views

315 citations