Redwing's video on quack cures

Nelson et al said...
Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead.

Nelson et al said...
Curcumin... is more like a missile that has shown excellent promise in early testing (in vitro), even though this testing may have been bedeviled by design problems that led to several misfires. The structure of [curcumin] suggests that it might be unstable in a biological setting, and in fact, it is: both its in vitro and in vivo stabilities are abysmal (halflife < 5 min)relative to commercial drugs.

To our knowledge, curcumin has never been shown to be conclusively effective in a randomized, placebo-controlled clinical trial for any indication.Curcumin is best typified, therefore, as a missile that continually blows up on the launch pad, never reaching the atmosphere or its intended target(s).

Curcumin is a PAINS, IMP and Poor lead compound. PAINS, or pan-assay interference compounds, are compounds that have been observed to show activity in multiple types of assays by interfering with the assay readout rather than through specific compound/target interactions.

From a collective point of view, IMPS are invalid metabolic panaceas located inside the center of the black hole of natural products that tend to exhaust research resources. As singular elements, IMPS are prototypes of improbable metabolic panaceas that exhibit feeble performance as drug leads.

A prototypical lead compound for therapeutic discovery and development generally has less than 1 μM potency at its desired target(s), evidence of selectivity and tractable mechanism(s) of action, good bioavailability, chemical stability, and ADMET (absorption, distribution, metabolism, excretion, and toxicology) qualities that can be optimized in a reasonable number of synthetic cycles. [Curcumin]has none of these features.

With respect to curcumin/curcuminoids and in vivo studies and clinical trials, we believe there is rather “much ado about nothing”. Certainly, the low systemic exposure levels reported in clinical trials do not support its further investigation as a therapeutic.