A Kernel for Open Source Drug Discovery in Tropical Diseases

Open source drug discovery, a promising alternative avenue to conventional patent-based drug development, has so far remained elusive with few exceptions. A major stumbling block has been the absence of a critical mass of preexisting work that volunteers can improve through a series of granular contributions. This paper introduces the results from a newly assembled computational pipeline for identifying protein targets for drug discovery in ten organisms that cause tropical diseases. We have also experimentally tested two promising targets for their binding to commercially available drugs, validating one and invalidating the other. The resulting kernel provides a base of drug targets and lead candidates around which an open source community can nucleate. We invite readers to donate their judgment and in silico and in vitro experiments to develop these targets to the point where drug optimization can begin

CCN3 modulates bone turnover and is a novel regulator of skeletal metastasis

The CCN family of proteins is composed of six secreted proteins (CCN1-6), which are grouped together based on their structural similarity. These matricellular proteins are involved in a large spectrum of biological processes, ranging from development to disease. In this review, we focus on CCN3, a founding member of this family, and its role in regulating cells within the bone microenvironment. CCN3 impairs normal osteoblast differentiation through multiple mechanisms, which include the neutralization of pro-osteoblastogenic stimuli such as BMP and Wnt family signals or the activation of pathways that suppress osteoblastogenesis, such as Notch. In contrast, CCN3 is known to promote chondrocyte differentiation. Given these functions, it is not surprising that CCN3 has been implicated in the progression of primary bone cancers such as osteosarcoma, Ewing’s sarcoma and chondrosarcoma. More recently, emerging evidence suggests that CCN3 may also influence the ability of metastatic cancers to colonize and grow in bone

Production of innovative radionuclides for medical applications at the CERN-MEDICIS facility

Since its commissioning in December 2017, the CERN-MEDICIS facility has been providing non-conventional radionuclides for research in nuclear medicine. Benefitting from decades of experience in the production of radioactive ion beams and in the mass separation process from the ISOLDE facility at CERN, MEDICIS quickly became a worldwide key player in the supply of novel medical isotopes dedicated to research in the fields of cancer imaging, diagnostics, and radiation therapy. After a few years of operation, successful collections have been performed on a large panel of radionuclides such as 128Ba, 149,152,155Tb, 153Sm, 165,167Tm, 169Er, 175Yb, 191Pt, and 225,227Ac. Several milestones have been achieved on the output of the facility, such as the collection of 0.5 GBq of 175Yb, and a total separation efficiency higher than 50% reached for 167Tm in 2020. These collections led to notable recent in-vitro and preclinical results in targeted radionuclide therapy achieved with high molar activity 175Yb and 153Sm products. Constant developments are ongoing, such as innovative target designs, molecular formation to improve the release of some specific isotopes, laser development in the dedicated MELISSA laboratory, study of new implantation foil materials, and post-collection radiochemistry