Dr. Sarlah from the University of Illinois has synthesized novel analogs and isotopologs of the anticancer isocarbostyril alkaloids lycoricidine and narciclasine. Currently, isocarbostyril alkaloids are low in natural abundance and have poor aqueous solubility. These new synthetic compounds exhibit improved metabolic activity, stability, and/or aqueous solubility.
Enantioselective Synthesis of Isocarbostyril Alkaloids and Analogs Using Catalytic Dearomative Functionalization of Benzene. Bingham, et al. Dec 6, 2018.
Dr. Paul Hergenrother fhas developed a new series of broad spectrum fusidic acid derivatives. Designed using two distinct methodologies, these fusidic acid derivatives...
Dr. Paul Hergenrother fhas developed a new series of broad spectrum fusidic acid derivatives. Designed using two distinct methodologies, these fusidic acid derivatives feature unique side chains and demonstrate improved MIC values when compared with fusidic acid. One series of derivatives displays antibiotic activity against Gram-negative ESKAPE pathogens, including in clinical isolates of P. aeruginosa. The prodrug displays low toxicity in mammalian cells and human serum experiments suggest that it is less protein bound than Fusidic Acid. A second series of derivatives displays potent activity against clinical isolates of Staphylococcus aureus and Enterococcus faecium and an improved resistance profile in vitro and in vivo when compared to fusidic acid. Additionally, these derivatives display in vivo efficacy against an FA-resistant strain of Staphylococcus aureus in a mouse infection model.
This cancer treatment material and approach is a less invasive, more targeted alternative for treating radiation-sensitive tumors. A novel mechanophore-containing hydrogel...
This cancer treatment material and approach is a less invasive, more targeted alternative for treating radiation-sensitive tumors. A novel mechanophore-containing hydrogel is deposited at the tumor site and high-intensity focused ultrasound (HIFU) is used to locally generate cytotoxic reactive oxygen species (ROS) through an approach we call mechanochemical dynamic therapy (MDT). MDT dramatically decreases non-tumor cytotoxicity caused by conventional radiation treatments, which have to deliver damaging radiation through layers of healthy tissue to reach a tumor. Since HIFU can penetrate deep into and through tissues—including bone—MDT has the potential to significantly increase the number of tumors that are candidates for minimally invasive treatment. These combined features of targeted treatment (inaccessible through sonodynamic therapies) and the ability to treat deep-seated tumors (inaccessible through photodynamic therapy) makes MDT an extremely promising new approach for effective tumor treatment with minimal side effects.
Benefits:
Reduces side effects compared to photodynamic and sonodynamic therapies
Immune therapy is a revolutionary cancer treatment that has significantly developed in the last decade. Breast tumors are highly immune-suppressive with a limited number...
Immune therapy is a revolutionary cancer treatment that has significantly developed in the last decade. Breast tumors are highly immune-suppressive with a limited number of therapies available leading to high recurrence and mortality. T-cells naturally maintain an immune-suppressed cell environment which further reduce successful patient outcomes. These are small molecules targeting the NR0B2 transcriptional regulator for treatment of solid tumors. These compounds lead to reduction of T regulatory cells (Treg) expansion and shows strong efficacy against metastatic mammary, lung and sarcoma tumors in mouse models (e.g., inhibits induction of the ABCA1 gene, affects T cell expansion, attenuates IL-1beta mRNA, and retains cell viability).
Benefits
Effective against solid tumors, which are often treatment resistant.
Significantly reduced the outgrouth of metastatic lesions.
Elicits a reduction in T cell expansion using a lower dose.
Orally available.
Crosses the brain blood barrier.
Publications
Hashni Epa Vidana Gamage, Sayyed Hamed Shahoei, Yu Wang, Elise Jacquin, Erin Weisser, Rafael O. Bautista, Madeline A. Henn, Claire P. Schane, Adam T. Nelczyk, Liqian Ma, Anasuya Das Gupta, Shruti V. Bendre, Tiffany Nguyen, Srishti Tiwari, Evelyn Tjoanda, Natalia Krawczynska, Sisi He, Samuel T. Albright, Rachel Farmer, Amanda J. Smith, Emma C. Fink, Hong Chen, Maria Sverdlov, Peter H. Gann, Romain Boidot, Frederique Vegran, Sean W. Fanning, Paul J. Hergenrother, Lionel Apetoh, Erik R. Nelson, NR0B2 re-educates myeloid immune cells to reduce regulatory T cell expansion and progression of breast and other solid tumors, Cancer Letters, Volume 597, 2024, 217042, ISSN 0304-3835, https://doi.org/10.1016/j.canlet.2024.217042.
Hashni Epa Vidana Gamage, Samuel T. Albright, Amanda J. Smith, Rachel Farmer, Sayyed Hamed Shahoei, Yu Wang, Emma C. Fink, Elise Jacquin, Erin Weisser, Rafael O. Bautista, Madeline A. Henn, Claire P. Schane, Adam T. Nelczyk, Liqian Ma, Anasuya Das Gupta, Shruti V. Bendre, Tiffany Nguyen, Srishti Tiwari, Natalia Krawczynska, Sisi He, Evelyn Tjoanda, Hong Chen, Maria Sverdlov, Peter H. Gann, Romain Boidot, Frederique Vegran, Sean W. Fanning, Lionel Apetoh, Paul J. Hergenrother, Erik R. Nelson, Development of NR0B2 as a therapeutic target for the re-education of tumor associated myeloid cells, Cancer Letters, Volume 597, 2024, 217086, ISSN 0304-3835, https://doi.org/10.1016/j.canlet.2024.217086.
