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

A facile route for the synthesis of sub-micron sized hollow and multiporous organosilica spheres

We present a facile route for the synthesis of sub-micron sized hollow and multiporous organosilica spheres, which is based on an oil-in-water emulsion and merely uses one organosilica precursor-phenyl trimethoxysilane-that serves as monomer, precursor for a surface active species and oil phase. This journal is © the Partner Organisations 2014

Synthesis of sub-micron sized hollow, and nanoporous phenylsiloxane spheres through use of phenyltrimethoxysilane as surfmer: Insights into the surfactant and factors influencing the particle architecture

Recently, our group reported synthesis routes for sub-micron sized hollow, and nanoporous phenylsiloxane spheres, in which phenyltrimethoxysilane is applied as surfmer. Here, we present insights into the surfactant formed through hydrolytic conversion of phenyltrimethoxysilane, and factors influencing the particle architecture. cop. 2016 Elsevier B.V

Synthesis and characterization of hybrid particles obtained in a one-pot process through simultaneous sol-gel reaction of (3-mercaptopropyl)trimethoxysilane and emulsion polymerization of styrene

Hybrid particles consisting of an organic polymer and silica or polyorganosiloxanes are interesting building blocks for nanocomposites. The synthesis of such particles typically requires multiple reaction steps involving the formation of polymer colloids and the subsequent deposition of silicon-containing material either inside or on the surface of these colloids, or vice versa. In 2014, we reported a facile method for the one-pot synthesis of sub-micron sized hybrid particles based on simultaneous sol-gel conversion of organotrimethoxysilanes and emulsion polymerization of a vinylic monomer, illustrated by the synthesis of polystyrene-polyphenylsiloxane particles from the monomers styrene and phenyltrimethoxysilane (Segers et al (2014). In this process, the required surface active species was formed in situ through hydrolytic conversion of phenyltrimethoxysilane to phenylsilanolate oligomers. Introduction of thiol groups in such hybrid particles should yield particles suited for functionalization with small metal nanoparticles, e.g., Au. Here, we present the synthesis of thiol-containing hybrid particles consisting of poly(3-mercaptopropyl)siloxane and polystyrene using the one-pot synthesis method based on simultaneous conversion of (3-mercaptopropyl)trimethoxysilane and styrene. We prepared particles from different volume ratios of (3-mercaptopropyl)trimethoxysilane and styrene, ranging from 1:99 to 80:20. The resulting spherical hybrid particles displayed different sizes, compositions, and architectures (including core-shell), which were studied in detail using scanning electron microscopy, thermogravimetric analysis, and scanning transmission electron microscopy combined with energy dispersive x-ray spectroscopy. The composition of these particles, and consequently the number of thiol groups available for further functionalization such as metal anchoring, was tunable

Stranding of pygmy sperm whale, Kogia breviceps (de Blainville, 1838), in eastern French Guiana

This short communication presents the first stranding record for pygmy sperm whale in French Guiana

Facile and Versatile Platform Approach for the Synthesis of Submicrometer-Sized Hybrid Particles with Programmable Size, Composition, and Architecture Comprising Organosiloxanes and/or Organosilsesquioxanes

We present a facile and versatile platform approach for the synthesis of submicrometer-sized hybrid particles based on an oil-in-water emulsion. These particles comprise organosiloxanes and/or organosilsesquioxanes formed via hydrolysis and polycondensation of alkyl- or aryltrimethoxysilane, and polystyrene or poly­(methyl methacrylate) formed through radical polymerization of styrene and methyl methacrylate, respectively. In this synthesis, the alkyl- or aryltrimethoxysilane fulfills three different roles: (i) it is part of the oil phase, (ii) serves as monomer for the formation of the organosiloxane network, and (iii) forms a surface active species that stabilizes the emulsion. Size, composition and architecture of the resulting hybrid particles are programmable in this synthetic approach, as demonstrated for the combination phenyltrimethoxysilane/styrene. The versatility of the approach is demonstrated by preparing hybrid particles based on following precursor/monomer combinations: phenyltrimethoxysilane/methyl methacrylate, methyltrimethoxysilane/styrene, (3-acryloxypropyl)­trimethoxysilane/styrene and (3-mercaptopropyl)­trimethoxysilane/styrene. Latter combination yields hybrid spheres with thiol groups suited for further functionalization

Apixaban for Extended Treatment of Venous Thromboembolism

BACKGROUND Apixaban, an oral factor Xa inhibitor that can be administered in a simple, fixed-dose regimen, may be an option for the extended treatment of venous thromboembolism. METHODS In this randomized, double-blind study, we compared two doses of apixaban (2.5 mg and 5 mg, twice daily) with placebo in patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy and for whom there was clinical equipoise regarding the continuation or cessation of anticoagulation therapy. The study drugs were administered for 12 months. RESULTS A total of 2486 patients underwent randomization, of whom 2482 were included in the intention-to-treat analyses. Symptomatic recurrent venous thromboembolism or death from venous thromboembolism occurred in 73 of the 829 patients (8.8%) who were receiving placebo, as compared with 14 of the 840 patients (1.7%) who were receiving 2.5 mg of apixaban (a difference of 7.2 percentage points; 95% confidence interval [CI], 5.0 to 9.3) and 14 of the 813 patients (1.7%) who were receiving 5 mg of apixaban (a difference of 7.0 percentage points; 95% CI, 4.9 to 9.1) (P <0.001 for both comparisons). The rates of major bleeding were 0.5% in the placebo group, 0.2% in the 2.5-mg apixaban group, and 0.1% in the 5-mg apixaban group. The rates of clinically relevant nonmajor bleeding were 2.3% in the placebo group, 3.0% in the 2.5-mg apixaban group, and 4.2% in the 5-mg apixaban group. The rate of death from any cause was 1.7% in the placebo group, as compared with 0.8% in the 2.5-mg apixaban group and 0.5% in the 5-mg apixaban group. CONCLUSIONS Extended anticoagulation with apixaban at either a treatment dose (5 mg) or a thromboprophylactic dose (2.5 mg) reduced the risk of recurrent venous thromboembolism without increasing the rate of major bleeding. (Funded by Bristol-Myers Squibb and Pfizer; AMPLIFY-EXT ClinicalTrials.gov number, NCT00633893.