ANNOUNCEMENT!! New Product Released!!
ReLeaf™ Pain Reliever - a unique natural pain reliever that is more effective, non-addicting and natural!
E Pluribus Unum - "Out of Many, One"
You should all recognize this phrase, it is on most currency in the United States. It is a perfect start to our new pain reliever product.
In fact, our first series is more "Out of 1 million, One"
One of the ingredients in our new ReLeaf® product had rigorous testing to be found, incarvillea sinensis.
A study was performed on 1,000,00 compounds to screen out top pain relief candidates via a pain relief "score."
Getting technical, hang in there. Traditionally, many screening programs such as "DOCK", employ a simple two-term scoring function (score) consisting of intermolecular van der Waals and electrostatic terms to rank-order compatibility of ligands with a target. Van der What? Google it.
In this work, they utilized a new scoring function termed molecular footprint similarity (FPS) score in which the standard DOCK energy score is decomposed into per-residue
contributions. The method was recently employed in the successful discovery of novel HIVgp41 inhibitors. The procedure can be used to identify which compounds are most energetically similar to a known reference. In human speak, is there something similar to morphine, that say, doesn't have addiction properties.
Fatty acid binding proteins (FABPs), in particular FABP5 and FABP7, have recently been identified by us as intracellular transporters for the endocannabinoid anandamide (AEA). Animal studies by others have shown that elevated levels of endocannabinoids resulted in beneficial pharmacological effects on stress, pain and inflammation and also ameliorate the effects of drug withdrawal (precursor to addiction). Based on these observations, the study investigators hypothesized that FABP5 and FABP7 would provide excellent pharmacological targets. Thus, they performed a virtual screening of over one million compounds using DOCK and employed a novel footprint similarity scoring function, that we talked about earlier, to identify lead compounds with binding profiles similar to oleic acid, a natural FABP substrate.
Out of 1 million compounds, Forty-eight were shown to have significant activity with this score and were purchased based on their footprint similarity scores (FPS) and assayed for biological activity against purified human FABP5 employing a fluorescent displacement-binding assay for a deeper look. Four compounds were found to exhibit approximately 50% inhibition or greater at 10 mM, as good as or better inhibitors of FABP5 than BMS309403, a commercially available inhibitor. Down to the final four!
The most potent inhibitor, c-truxillic acid 1-naphthyl ester (ChemDiv 8009-2334), was determined to have Ki value of 1.1960.01 mM. Accordingly a novel a-truxillic acid 1-naphthyl mono-ester (named "SB-FI-26" - cause scientists can't name things using easy terminology like "Herman" or "Shiny Object" compound) was synthesized and assayed for its inhibitory activity against FABP5.
Amazingly, SB-FI-26 exhibited strong binding (Ki 0.9360.08 mM), stronger than all other 999,999 compounds!
Truxillic acids and their derivatives were also shown by others to have anti-inflammatory and anti-nociceptive ("anti pain") effects in mice and to be the active component of a Chinese a herbal medicine (using a plant called, incarvillea sinensis) used to treat rheumatism and pain in humans.
For over 5000 years, this was used in hot tea and drank in a timeframe of 30 mins. The compound found to be the potent extract in this plant, is the exact structure of "SB-Fl-26" - known today as incarvillateine.
Incarvillea sinensis, as the whole plant, and incarvillateine as the key extract, is one of our lead patent pending formulations for our new Releaf™ Pain reliever!
"Supporting ReLeaf™ from chronic pain, muscle aches, and headaches!"
"E decies centena, unum!!" | "Out of 1 Million, One!"
References
(pdf download below for reference)
DOCK6.5 (2011) San Francisco, CA: University of California at San Francisco.
Balius TE, Mukherjee S, Rizzo RC (2011) Implementation and evaluation of a docking-rescoring method using molecular footprint comparisons. J Comput Chem 32: 2273–2289.
Holden PM, Kaur H, Gochin M, Rizzo RC (2012) Footprint-based identification of HIVgp41 inhibitors. Bioorg Med Chem Lett ss: 3011–3016.