Discovery of Ligands for TRIM58, a Novel Tissue-Selective E3 Ligase.

Redirecting E3 ligases to neo-substrates, leading to their proteasomal disassembly, known as targeted protein degradation (TPD), has emerged as a promising alternative to traditional, occupancy-driven pharmacology. Although the field has expanded tremendously over the past years, the choice of E3 ligases remains limited, with an almost exclusive focus on CRBN and VHL. Here, we report the discovery of novel ligands to the PRY-SPRY domain of TRIM58, a RING ligase that is specifically expressed in erythroid precursor cells.

Discovery of Potent and Selective Antibody-Drug Conjugates with Eg5 Inhibitors through Linker and Payload Optimization.

Targeted antimitotic agents are a promising class of anticancer therapies. Herein, we describe the development of a potent and selective antimitotic Eg5 inhibitor based antibody-drug conjugate (ADC). Preliminary studies were performed using proprietary Eg5 inhibitors which were conjugated onto a HER2-targeting antibody using maleimido caproyl valine-citrulline para-amino benzocarbamate, or MC-VC-PABC cleavable linker.

Natural product drug delivery: A special challenge?

Natural products have a long-standing and critical role in drug development and medical use. The structural and physicochemical properties of natural products, while derived evolutionarily to be effective in living systems, may create challenges in translation to a pharmaceutical product. Molecular complexity, low solubility, functional group reactivity and general instability are among the challenges that typically need to be overcome.

Assessing Private and Public Need for Uniqueness: Validation of French Versions of the Need for Uniqueness (NfU) and Self-Attributed Need for Uniqueness (SANU) Scales.

Need for uniqueness represents the need for people to feel different and distinguish themselves from others. Two major scales exist that measure this need: the Need for Uniqueness scale (NfU; Snyder & Fromkin, 1977 ) and the Self-Attributed Need for Uniqueness scale (SANU; Lynn & Harris, 1997b ). We propose here a French version of both scales.

Performance-based everyday functional competence measures across the adult lifespan: the role of cognitive abilities.

Background: The effects of age on the ability to manage everyday functioning, crucial to ensure a healthy aging process, have been rarely examined and when, self-report measures have been used. The aim of the present study was to examine age effects across the adult lifespan in everyday functioning with two performance-based measures: the Everyday Problems Test (EPT), and the Timed Instrumental Activities of Daily Living (TIADL) tasks. The role of some crucial cognitive abilities, i.