AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Recommendations of the Oligonucleotide Safety Working Group’s Formulated Oligonucleotide Subcommittee for the Safety Assessment of Formulated Oligonucleotide-Based Therapeutics

The use of lipid formulations has greatly improved the ability to effectively deliver oligonucleotides and has been instrumental in the rapid expansion of therapeutic development programs employing oligonucleotide drugs. However, the development of such complex, multi-component therapeutics requires the implementation of unique, scientifically sound approaches based upon a hybrid of knowledge and experiences drawn from small-molecule, protein and oligonucleotide therapeutic drug development. The relative paucity of directly applicable regulatory guidance documents for oligonucleotide therapeutics in general has resulted in the generation of multiple white papers from oligonucleotide drug development experts and members of the Oligonucleotide Safety Working Group (OSWG). The members of the Formulated Oligonucleotide Subcommittee of the OSWG have utilized their collective experience working with a variety of formulations and their associated oligonucleotide ‘payloads’, as well as their insights into regulatory considerations and expectations, to generate a series of consensus recommendations for the pharmacokinetic characterization and nonclinical safety assessment of this unique class of therapeutics

Microscopic description of fission in neutron-rich radium isotopes with the Gogny energy density functional

Mean-field calculations, based on the D1S, D1N and D1M parametrizations of the Gogny energy density functional, have been carried out to obtain the potential energy surfaces relevant to fission in several Ra isotopes with the neutron number $144\le N\le 176$. Inner and outer barrier heights as well as first and second isomer excitation energies are given. The existence of a well-developed third minimum along the fission paths of Ra nuclei is analyzed in terms of the energetics of the “fragments” defining such elongated configuration. The masses and charges of the fission fragments are studied as functions of the neutron number in the parent Ra isotope. The comparison between fission and $\alpha$ -decay half-lives, reveals that the former becomes faster for increasing neutron numbers. Though there exists a strong variance of the results with respect to the parameters used in the computation of the spontaneous fission rate, a change in tendency is observed at $N=164$ with a steady increase that makes heavier neutron-rich Ra isotopes stable against fission, diminishing the importance of fission recycling in the r-process