The Ecstasy and Agony of Assay Interference Compounds

Predicted Biological Activity of Purchasable Chemical Space

“…Based on our experience with these encounters, we changed the baseline affinity threshold to 1 μM and further required activities of at least 100 nM for compounds containing PAINS patterns or being Tc 0.70 to any compound observed to aggregate. 48 − 50 …”

LEGO‐Inspired Drug Design: Unveiling a Class of Benzo[d]thiazoles Containing a 3,4‐Dihydroxyphenyl Moiety as Plasma Membrane H+‐ATPase Inhibitors

“…As the compoundsi nhibit Pma1p activity both in assays of ATPh ydrolytic activity as well as H + pumping, we are confident that they are Pma1pi nhibitors and do not act as pan-assay interference compounds (PAINS). [22] In conclusion, our present work demonstrated al ibrary of 2-(benzo[d]thiazol-2-ylthio)-1-(3,4-dihydroxyphenyl)ethanones as potentialf ungal protonp ump (Pma1p)i nhibitors and paved a new route for drug discovery towardtargets with limited structural information. Overall, we believe the workflow described for our approach could be ag uideline for medicinalc hemists in other studies of drug discovery and development pursuing less-well-described targets.…”

“…The precipitate was filtered and washed (3 10 mL) with CH 3 CN, EtOH, hot acetone, followed by recrystallization in EtOH to afford clean 1-15 as hydrochloride salts. General synthetic procedure for compounds [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30].Am ixture of 1-(substituted phenyl)ethan-1-one (1 equiv), copper(II) bromide (1 equiv), and 8mLo famixture of ethyl acetate/dichloromethane (1:1) was added to a2 0mLm icrowave reaction vial (Biotage). The vial was sealed and irradiated in am icrowave apparatus at 60 8C, high absorption for 15 min.…”

“…The crude product above was dissolved in 20 mL of CH 3 CN and the appropriately substituted heterocyclic thiol (1 equiv) was added and stirred at room temperature for 30 min until the appearance of as olid precipitate. The precipitate was then filtered and fast washed (3 10 mL) with each of CH 3 CN, EtOH, and hot acetone, followed by recrystallization in EtOH to afford clean [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] [1,4]dioxin-6-yl)-2-(quinolin-2-ylthio)ethan-1-one (16) Synthesis of 32-46:C ompounds 32-46 were synthesized using the same procedure as described for 1-15 from 31 a-o using microwave methodology (exception to workup procedure:a cidified to pH 4b yc onc. HBr instead of HCl, and products were collected as hydrobromide salts).…”

Scouting around 1,2,3,4‐Tetrahydrochromeno[3,2‐c]pyridin‐10‐ones for Single‐ and Multitarget Ligands Directed towards Relevant Alzheimer's Targets

“…In order to rule out artifacts in the screening protocol, an in-silico analysis was computed in the search for pan assay interference compounds (PAINS). [13] Two computational tools (ZINC15 pattern identifier [14] and PAINS remover [15] ) did not alert for any PAINS or aggregators. All compounds (1 de, 2 a) passed the filter "A, B, C" in FAF-Drugs4 web service, [16] whereas 2 a was discriminated as undesirable moiety embedding the risk of covalent attachment to nucleophiles, as could be expected from the presence of Michael acceptor functionality.…”