A Sivachenko

AL Harvey

B Fantin

B Papp

BA Larder

Chu Qin

Chun Yan Tan

CM Overall

Cun Long Zhang

Daniel S. Sem

DJ Newman

DM Eisenberg

DX Kong

EF Carvalho-Netto

EM Williamson

EW Sayers

F Zhu

FR Stermitz

GA Cordell

GG Zhang

GR Zimmermann

GT Lewith

GV Georgakis

H Quach

H Wagner

H Xiong

H Yang

HA Junio

HS Kim

J Gertsch

J Jia

J Kaiser

JE Dancey

JH MacIndoe

JI Johnson

JW Li

K Hayashi

Kai Leng Tan

KS Smalley

L Dinan

L Xie

LJ Li

LL Silver

M Shabbir

M Thanou

NV Sergina

P Csermely

PH Chiu

R Barker Bausell

R Muller

R Staud

RH Shoemaker

T Efferth

TC Chou

TF Molinski

TI Oprea

W Kassouf

X Tong

XH Ma

XM Zhou

Y Pilpel

Yu Yang Jiang

Yu Zong Chen

PLoS ONE

PubMed

Qin Chu

Tan Kai Leng

Zhang Cun Long

Tan Chun Yan

Chen Yu Zong

Jiang Yu Yang

Public Library of Science (PLOS)

What Does It Take to Synergistically Combine Sub-Potent Natural Products into Drug-Level Potent Combinations?

<div><p>There have been renewed interests in natural products as drug discovery sources. In particular, natural product combinations have been extensively studied, clinically tested, and widely used in traditional, folk and alternative medicines. But opinions about their therapeutic efficacies vary from placebo to synergistic effects. The important questions are whether synergistic effects can sufficiently elevate therapeutic potencies to drug levels, and by what mechanisms and at what odds such combinations can be assembled. We studied these questions by analyzing literature-reported cell-based potencies of 190 approved anticancer and antimicrobial drugs, 1378 anticancer and antimicrobial natural products, 99 natural product extracts, 124 synergistic natural product combinations, and 122 molecular interaction profiles of the 19 natural product combinations with collective potency enhanced to drug level or by >10-fold. Most of the evaluated natural products and combinations are sub-potent to drugs. Sub-potent natural products can be assembled into combinations of drug level potency at low probabilities by distinguished multi-target modes modulating primary targets, their regulators and effectors, and intracellular bioavailability of the active natural products.</p> </div

Chu Qin (115759)

Kai Leng Tan (115760)

Cun Long Zhang (115763)

Chun Yan Tan (115766)

Yu Zong Chen (113383)

Yu Yang Jiang (115770)

The Francis Crick Institute

Crossref

There have been renewed interests in natural products as drug discovery sources. In particular, natural product combinations have been extensively studied, clinically tested, and widely used in traditional, folk and alternative medicines. But opinions about their therapeutic efficacies vary from placebo to synergistic effects. The important questions are whether synergistic effects can sufficiently elevate therapeutic potencies to drug levels, and by what mechanisms and at what odds such combinations can be assembled. We studied these questions by analyzing literature-reported cell-based potencies of 190 approved anticancer and antimicrobial drugs, 1378 anticancer and antimicrobial natural products, 99 natural product extracts, 124 synergistic natural product combinations, and 122 molecular interaction profiles of the 19 natural product combinations with collective potency enhanced to drug level or by >10-fold. Most of the evaluated natural products and combinations are sub-potent to drugs. Sub-potent natural products can be assembled into combinations of drug level potency at low probabilities by distinguished multi-target modes modulating primary targets, their regulators and effectors, and intracellular bioavailability of the active natural products

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Younes A

Yuryev A

http://dx.doi.org/10.1371/journal.pone.0049969

What Does It Take to Synergistically Combine Sub-Potent Natural Products into Drug-Level Potent Combinations?

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Public Library of Science (PLOS)

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Directory of Open Access Journals