Inverse AGONIST

women than men. People not diagnosed make up the majority of thyroid patients. There is a need to find novel and safe
ways to change the underlying disease processes, rather than merely stop excess thyroid hormone production as in
hyperthyroidism.
Metadichol® is a nano emulsion of an extract of long-chain alcohols from food that is an inverse agonist of VDR
(Vitamin D receptor), AHR (Aryl Hydrocarbon Receptor), and RORC (RAR Related Orphan Receptor C). The work
presented here shows that Metadichol® is an inverse agonist of THRA (Thyroid Receptor Alpha) and THRB (Thyroid
Receptor Beta). Case studies are presented that show how it can safely treat a multitue of thyroid related diseases.
Network and pathway enrichment studies are presented that show how Metadichol® may be involved in action on
multiple receptors and exerting its effects through multiple pathways. Metadichol® is the first of a breed of molecules
that moves the goal post from the concept of ‘one drug, one target’ toward simultaneously targeting multiple targets, that
can potentially lead to successful treatment of many diseases. Given the safety profile of Metadichol®, it would not only
mitigate thyroid disease but prevent it and reducing the burden on healthcare budgets worldwide.

The novel imidazothienodiazepine inverse agonist RO19-4603 has been reported to attenuate EtOH intake in home cage drinking tests for at least 24 h post-drug administration after systemic administration. In the present study, selectively bred alcohol-preferring (P) ...

Selective cyclooxygenase-2 (COX-2) inhibitors have been shown to be potent antiinflammatory agents with fewer side effects than currently marketed nonsteroidal antiinflammatory drugs (NSAIDs). Initial mass screening and subsequent structure-activity relationship (SAR) studies have identified 4b (PD138387) as the most potent and selective COX-2 inhibitor within the thiazolone and oxazolone series of di-tert-butylphenols. Compound 4b has an IC50 of 1.7 microM against recombinant human COX-2 and inhibited COX-2 activity in the J774A.1 cell line with an IC50 of 0.17 microM. It was inactive against purified ovine COX-1 at 100 microM and did not inhibit COX-1 activity in platelets at 20 microM. Compound 4b was also orally active in vivo with an ED40 of 16 mg/kg in the carrageenan footpad edema (CFE) assay and caused no gastrointestinal (GI) damage in rats at the dose of 100 mg/kg but inhibited gastric prostaglandin E2 (PGE2) production in rats' gastric mucosa by 33% following a dose o...

New pathogenic virus outbreaks with increasing regularity are leading us to explore novel approaches, which will reduce the reliance on a time-consuming vaccine mode to halt the strike. The requirement is to find a universal approach to disarm any new and as yet unknown viruses as they appear. A promising approach could be by targeting the lipids membranes, common to all viruses and bacteria.
The ongoing pandemic of the SARS-coronavirus 2 (SARS-CoV-2) has restated the importance of interactions between components of the host cell plasma membrane and the virus envelope as a critical mechanism of infection. Metadichol ®, a nano lipid emulsion, has been examined and shown to be a strong candidate to help stop the proliferation of the SARS-COV-2.
Naturally derived substances, such as Cyclodextrin and sterols, reduce the infectivity of various types of viruses, including the coronavirus like SARS-COV-2, by modifying the lipid-dependent attachment to human host cells. SARS-COV-2 uses the receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming.
Metadichol®, a nano lipid formulation of long-chain alcohols, has been shown to inhibit TMPRSS2 (EC50 of 96 ng/ml). Compared to the inhibitor Camostat Mesylate (26000 ng/ml), it is 270 times more potent. Also, Metadichol ® is a moderate inhibitor of ACE2 @ 31 µg/ml. In the SARS-COV2 anti-viral assay using CACO2 cells, it has an EC90 of 0.16 µg/ml.

The ability of naltrexone (NTX) to potentiate the propunishment and convulsant properties of DMCM, a benzodiazepine receptor inverse agonist, was studied in mice. Doses (0.39 and 1.56 mg/kg) of DMCM which were below the threshold for propunishment effects showed a marked ability to enhance the suppressive effects of punishment on locomotor activity in the presence of naltrexone (0.5 or 2.5 mg/kg IP), higher doses of DMCM and NTX (3.13 mg/kg and 10 mg/kg, respectively) had a depressant effect of their own on both punished and unpunished locomotor activity. DMCM given alone induced clonic convulsions (ED50: 5.7 mg/kg IP) but this activity was not changed in the presence of naltrexone. These results suggest an interaction of BZ receptors and opioid systems in the control of anxiety.

A novel series of 1-sulfonyl-4-acylpiperazines as selective cannabinoid-1 receptor (CB1R) inverse agonists was discovered through high throughput screening (HTS) and medicinal chemistry lead optimization. Potency and in vivo properties were systematically optimized to afford ...