2020
DOI: 10.1101/2020.03.30.017244
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Systematic Chemogenetic Library Assembly

Abstract: The assembly of chemogenetic libraries composed of chemical probes provides tremendous value to biomedical research, but requires substantial effort to ensure diversity as well as quality of the contents. We are assembling a chemogenetic library by data mining and crowdsourcing institutional expertise. We are sharing our methodology, lessons learned, and disclosing our current collection of 4186 compounds with their primary annotated gene targets.

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Cited by 18 publications
(24 citation statements)
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“…To find target proteins whose functions might be modulated to enhance T-cell-mediated tumor cytotoxicity, we employed the spheroid-killing IO platform in a chemical genomics screen of 1770 annotated compounds with known or suspected targets or mechanisms of action (MoAs) 20 . The compound collection screened during this initiative was a subset of the library described in 20 and consisted of low molecular weight targeted perturbagens covering more than 16 different protein and enzyme classes ( Supplementary Fig. 4a).…”
Section: Screen For Enhancers Of T-cell-mediated Anti-tumor Functionmentioning
confidence: 99%
“…To find target proteins whose functions might be modulated to enhance T-cell-mediated tumor cytotoxicity, we employed the spheroid-killing IO platform in a chemical genomics screen of 1770 annotated compounds with known or suspected targets or mechanisms of action (MoAs) 20 . The compound collection screened during this initiative was a subset of the library described in 20 and consisted of low molecular weight targeted perturbagens covering more than 16 different protein and enzyme classes ( Supplementary Fig. 4a).…”
Section: Screen For Enhancers Of T-cell-mediated Anti-tumor Functionmentioning
confidence: 99%
“…High-throughput screening identifies modulators of naive human pluripotency in minimal conditions Our prior study, which resulted in the identification of the 5i/L/A cocktail, screened a library of 230 kinase inhibitors to identify compounds that can sustain naive-specific reporter activity in combination with 2i/LIF (Theunissen et al, 2014). Here, we considered whether alternative modulators of naive human pluripotency may be identified by repeating this screen on a highthroughput scale and applying a dynamic chemogenetic library of $3,000 chemical probes in which a well-defined target is known for each of the compounds (Novartis Mechanism of Action Box) (Canham et al, 2020) either in the presence or absence of 2i. Similar to our prior study, we used naive hESCs that were generated with doxycycline (Dox)-inducible transgenes driving exogenous KLF2 and NANOG transgenes (Theunissen et al, 2014).…”
Section: Resultsmentioning
confidence: 99%
“…However, a detailed understanding of the signaling requirements for inducing and maintaining naive human pluripotency has remained elusive. In an effort to expand the known repertoire of factors regulating naive human pluripotency, we performed high-throughput chemical screening using a library of $3,000 well-annotated compounds (Canham et al, 2020) to identify alternative compounds that can maintain naive hESCs in the absence of MEK and GSK3 inhibitors that are commonly included in naive stem cell protocols.…”
Section: Discussionmentioning
confidence: 99%
“…Briefly, the primary screen identified compounds that resulted in disproportional changes in either cell size or G1 length (off-axis compounds) 12 . We further investigated these compounds using internal Novartis libraries sourced from the publicly known subset of compounds in the Mechanism-of-Action (MOA) Box (Canham et al, 2020). The screen was performed in 384-well μclear microplates (Greiner Bio-one, Monroe, NC).…”
Section: Chemical Screenmentioning
confidence: 99%