Pharmaceuticals & Vitamin D

Most Recent Inventions

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.

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.

New and More Potent UGM Inhibitors for Treating Tuberculosis, Other Microbial Infections

UW–Madison researchers have developed a new set of UGM inhibitors to fight tuberculosis and other diseases caused by microbial infections. The compounds feature an N-acylsulfonamide motif and are more potent in vitro than inhibitors previously identified by the researchers.

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.

Inhibiting Metadherin/SND1 Interaction to Treat Cancer

UW–Madison researchers and collaborators have developed a method to fight tumor growth and metastasis using novel peptides that inhibit interaction between MTDH and a protein called SND1.

The researchers found that MTDH-SND1 protein interaction is important for the expansion and function of prostate tumors as well as luminal and basal breast tumor initiating cells. Their work provides novel peptides that target this protein complex to help control tumor initiation, recurrence and metastasis by combating tumor initiating cells, with minimal impact on normal tissues.

Most Recent Patents

Stable Collagen Mimics

UW-Madison researchers have developed several new collagen mimics that use steric, rather than stereoelectronic, effects to achieve increased stability. The collagen mimics consist of a tripeptide unit with the formula (Xaa-Yaa-Gly)n, where either Xaa or Yaa is a bulky, non-electron withdrawing, 4-substituted proline derivative that contains an alkyl or thiol group, and n is a positive integer of at least 3.

Replacing a proline derivative at the Xaa or Yaa position results in steric effects that increase the stability of the helix. Specifically, three collagen variants that are more stable than native collagen are (Pro-Mep-Gly)7, (mep-Pro-Gly)7 and (mep-Mep-Gly)7, where Mep is (2S,4S)-4-methylproline and mep is (2S,4R)-4-methylproline. In addition, a fluoroproline may be substituted at the Xaa or Yaa position to further increase the strength and stability of the collagen.

Non-Natural Peptides for Treating Diabetes

UW–Madison researchers have developed a new approach for designing GLP-1 receptor agonists that could be used to treat diabetes. The agonists retain GLP-1-like function but have prolonged activity in vivo.

The method includes strategically replacing native α-amino acid residues with conformationally constrained β-amino acid resides. The new α/β peptides mimic GLP-1 in terms of interacting with pancreatic beta cells and regulating blood glucose levels. The peptides are less susceptible to enzyme degradation due in part to the multiple β residue replacements.

Enhanced HIV Treatments: Boronic Acid Group Improves Drug Potency

UW–Madison researchers have developed new, more potent protease inhibitors, particularly aspartyl protease inhibitors such as those that inhibit HIV protease.

To make the new inhibitors, certain aryl groups in existing inhibitors are replaced with aryl boronic acid groups, leading to significantly enhanced activity. The boronic acid group may be protected with a protecting group that can be removed in vivo to provide an HIV protease inhibitor prodrug.