Chemical moieties associated with CYP inhibition.

<p>Chemical moieties associated with CYP inhibition.</p

A Design Approach for Collaboration Processes: A Multi-Method Design Science Study in Collaboration Engineering

Collaboration Engineering is an approach for the design and deployment of repeatable collaboration processes that can be executed by practitioners without the support of collaboration professionals such as facilitators. A critical challenge in Collaboration Engineering concerns how the design activities have to be executed and which design choices have to be made to create a process design. We report on a four year design science study, in which we developed a design approach for Collaboration Engineering thatincorporates existing process design methods, pattern based design principles, and insights from expert facilitators regarding design challenges and choices. The resulting approach was evaluated and continuously improved in four trials with 37 students. Our findings suggest that this approach is useful to support the design of repeatable collaboration processes. Our study further serves as an example of how a design approach can be developed and improved following a multi-method design science approach.Multi Actor SystemsTechnology, Policy and Managemen

Trends of control 1 (closed circles, solvent only control, 0% inhibition), control 2 (open circles, reaction in absence of bactosomes, 100% inhibition) and Z’ (grey squares) of representative high-throughput screening runs of <i>T</i>. <i>cruzi</i> CYP51 FLINT (a) and cytochrome c reductase absorbance (b) assays in 384 well format.

<p>Error bars are the standard deviations of 16 replicates for each control and plate.</p

IC₅₀ Determination of a test set of compounds.

<p>^<b>a</b> Coefficient of variation for all IC₅₀’s were lower than 1%</p><p>IC₅₀ Determination of a test set of compounds.</p

A Focused Screen Identifies Antifolates with Activity on Mycobacterium tuberculosis

Antifolates are widely used to treat several diseases but are not currently used in the first-line treatment of tuberculosis, despite evidence that some of these molecules can target Mycobacterium tuberculosis (Mtb) bacilli in vitro. To identify new antifolate candidates for animal-model efficacy studies of tuberculosis, we paired knowledge and tools developed in academia with the infrastructure and chemistry resources of a large pharmaceutical company. Together we curated a focused library of 2508 potential antifolates, which were then tested for activity against live Mtb. We identified 210 primary hits, confirmed the on-target activity of potent compounds, and now report the identification and characterization of 5 hit compounds, representative of 5 different chemical scaffolds. These antifolates have potent activity against Mtb and represent good starting points for improvement that could lead to in vivo efficacy studies