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In the single-dose pharmacokinetic experiments, compound 2b could be absorbed efficiently and metabolized smoothly in Wistar rats after oral administration.
Both broadly accessible data, such as Medline and Chembank, in addition to internal proprietary data of the company in the form of gene chip experiments, compound screening databases, and clinical trial information play an important role in the success of drug repositioning.
In these experiments, compound 16 showed a fairly strong inhibitory effect on thrombin-induced platelet aggregation, and demonstrated potent activity for inhibiting arteriovenous thrombosis with an inhibition rate of (73 ± 6) %, which was comparable to that of dabigatran etexilate (76 ± 2) %.
In further experiments, compound 25b having a beta configuration of the thymine moiety showed relatively strong growth inhibitory activity against cancer cell lines, and was more potent against all cancer cell lines than compound 26b, which carries a thymine moiety in the alpha configuration.
In these experiments, compound concentrations were expressed as a fraction of the IC50s of the compounds alone.
For in vivo experiments, compound purity was further analyzed by ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-MS), with all compounds found to be of ≥99% purity.
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In laboratory experiments, compounds based on similar cube-shaped molecules have shown some ability to bind to cancer cells and destroy them.
In test tube experiments, compounds that bind to these heavy metals dissolve the plaques.
In all experiments, compounds were used in concentrations below the minimal inhibitory concentration.
For replication experiments, compounds were cherry-picked from thawed DMSO stocks, spotted manually onto assay plates and processed as above.
In these experiments, compounds are assayed in serial blood samples in the minutes following either feeding or injection of a solution containing the compounds.
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