Pharmaceuticals & Vitamin D

Most Recent Inventions

New Hormone Analogs for Treating Hypoparathyroidism

UW–Madison researchers have developed backbone-modified analogs of PTH(1-34). The analogs exhibit advantageous properties; they are biased toward Gs activation/cAMP production relative to β arrestin recruitment.

The analogs were generated via an unconventional strategy in which the backbone of a natural PTHR-1 agonist was altered, rather than the side-chain complement. More specifically, selected α-amino acid residues were systemically replaced with either β-amino acid residues or with unnatural D-stereoisomer α-amino acid residues.

The researchers have shown that backbone-modification can rapidly identify potent agonists with divergent receptor-state selectivity patterns relative to a prototype peptide.

Nylon-3 Polymers to Treat Fungal Infections

UW–Madison researchers have found that nylon-3 polymers developed in their lab display potent antifungal activity against a broad spectrum of common fungal pathogens, with minimal toxicity towards mammalian cells. The polymers have some activity alone, and when used in combination with existing drugs provide synergistic effects against Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus strains, including some resistant strains.

Synergistic combination offers efficacy with significantly reduced amounts of drug and corresponding toxicity, which could potentially expand the relevant patient population.

The polymers were designed to resemble host-defense peptides (HDPs), which are natural molecules that exhibit antimicrobial activities.

Analogs of Diptoindonesin G for Breast Cancer Drug Development

UW–Madison researchers have synthesized analogs of Dip G that have shown a greater ability than the parent molecule to decrease ERα expression and stabilize ERβ in cultured breast cancer cells. The compounds are active for ameliorating, attenuating and halting the growth/metastasis of breast cancers.

Use of Salate Derivatives to Treat Multiple Sclerosis

UW–Madison researchers led by Prof. Hector DeLuca have discovered that two specific salate esters commonly found in sunscreen almost completely prevented experimental autoimmune encephalomyelitis (EAE) development in mice without affecting body weight. Salicylates are well-known nonsteroidal anti-inflammatory drugs (NSAIDs); the complete suppression of EAE by topical administration of homosalate and octyl salicylate is a novel finding.

Efficient In Vitro Assay for Antigen-Specific Tolerance

Building on their work, UW–Madison researchers have now developed a T cell-bound cytokine (T-CBC) assay for detecting and quantifying regulatory T cells specific to self-antigens or donor alloantigens. The new method comprises (a) culturing the subject’s T cells for 24 hours in the presence of one or more target antigens and (b) analyzing the cultured T cells for expression of a marker (EBi3; TGFβ/LAP) indicative of antigen-specific immune suppression.

Most Recent Patents

Compound Combination Targets Bacterial Virulence

The researchers have discovered that two lead compounds (E22/M64) can be combined to target multiple QS pathways at the same time (Rhl/Pqs), resulting in enhanced activity against P. aeruginosa and potentially other pathogens. This new cocktail approach is superior because it attenuates virulence factor production across a range of relevant environments where single compounds fail.

A Novel Series of Antimicrobials Target Bacteria Membranes to Overcome Antibiotic Resistance

UW–Madison researchers have developed a novel series of antimicrobial compounds that target the membranes of Gram-positive and Gram-negative bacteria, and are effective both against actively growing and stationary bacteria.

The series of compounds are analogs and derivatives of DCAP, or (2-((3-(3,6-dichloro-9H-carbazol-9-yl)-2-hydroxypropyl)amino)-2-(hydroxymethyl)propane-1,3-diol).

This series of compounds disrupts the bacterial cell envelope and causes cell death, and has only minor effects on eukaryotic cells. With this discovery, new antimicrobials based on DCAP analogs and derivatives could be used to combat resistant bacterial cells.

Combatting Biofilms by Disrupting Bacteria Quorum Sensing

UW–Madison researchers have developed a set of 2-aminobenzimidazole (2-ABI) derivatives that can almost totally inhibit or disperse biofilms by disrupting QS in Gram-negative bacteria, particularly P. aeruginosa. These small molecules have previously been shown to fight Gram-positive biofilm growth.

The compounds can be developed using known methods and applied in many forms, such as anti-biofilm coatings, hydrogels, disinfectants and pharmaceutical compositions. They work by acting as replacements for naturally occurring QS ligands in the ligand-protein binding system of bacteria. In this way, the compounds disturb coordination signals and thereby impede biofilm formation.