Proposing An Innovative Bond To Increase Investments In Social Drivers Of Health Interventions In Medicaid Managed Care.

Interventions to address social drivers of health (SDH), such as food insecurity, transportation, and housing, can reduce future health care costs but require up-front investment. Although Medicaid managed care organizations have incentives to reduce costs, volatile enrollment patterns and coverage changes may prevent them from realizing the full benefits of their SDH investments. This phenomenon results in the "wrong-pocket problem," in which managed care organizations underinvest in SDH interventions because they cannot capture the full benefit.

First-in-Class Dual Mechanism Ferroptosis-HDAC Inhibitor Hybrids.

HDAC inhibitors are an attractive class of cytotoxic agents for the design of hybrid molecules. Several HDAC hybrids have emerged over the years, but none combines HDAC inhibition with ferroptosis, a combination which is being extensively studied because it leads to enhanced cytotoxicity and attenuated neuronal toxicity. We combined the pharmacophores of and molecules to design the first-in-class dual mechanism hybrid molecules, which induce ferroptosis and inhibit HDAC proteins.

Pharmacophore optimization of imidazole chalcones to modulate microtubule dynamics.

We recently reported a new class of imidazole-based chalcones as potential antimitotic agents. In view of their promising cytotoxic activity, a comprehensive structure-activity relationship (SAR) of these compounds was undertaken focusing on four major structural variations: the length of the molecule, the Michael acceptor character, the nature and substitution pattern of ring B, and the nature of the amide functionality tethering ring B. These second-generation analogs (IBCs) demonstrated a superior bioactivity profile than the previously reported imidazole chalcones (referred to as IPEs).

C9ORF78 partially localizes to centromeres and plays a role in chromosome segregation.

C9ORF78 is a poorly characterized protein found in diverse eukaryotes. Previous work indicated overexpression of C9ORF78 in malignant tissues indicating a possible involvement in growth regulatory pathways. Additional studies in fission yeast and humans uncover a potential function in regulating the spliceosome.

A new class of cytotoxic agents targets tubulin and disrupts microtubule dynamics.

Despite the advances in treatment strategies, cancer is still the second leading cause of death in the USA. A majority of the currently used cancer drugs have limitations in their clinical use due to poor selectivity, toxic side effects and multiple drug resistance, warranting the development of new anticancer drugs of different mechanisms of action. Here we describe the design, synthesis and initial biological evaluation of a new class of antimitotic agents that modulate tubulin polymerization.