Chemical Genetic Screening for Compounds That Preferentially Inhibit Growth of Methylthioadenosine Phosphorylase (MTAP)–Deficient Saccharomyces cerevisiae
SLAS Discovery, ISSN: 2472-5552, Vol: 16, Issue: 1, Page: 44-52
2011
- 6Citations
- 18Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations6
- Citation Indexes6
- CrossRef4
- Captures18
- Readers18
- 18
Article Description
Methylthioadenosine phosphorylase (MTAP), a key enzyme in the methionine salvage pathway, is inactivated in a variety of human cancers. Since all human tissues express MTAP, it would be of potential interest to identify compounds that selectively inhibit the growth of MTAP-deficient cells. To determine if MTAP inactivation could be targeted, the authors have performed a differential chemical genetic screen in isogenic MTAP + and MTAP – Saccharomyces cerevisiae. A low molecular weight compound library containing 30,080 unique compounds was screened for those that selectively inhibit growth of MTAP – yeast using a differential growth assay. One compound, containing a 1,3,4-thiadiazine ring, repeatedly showed a differential dose response, with MTAP – cells exhibiting a 4-fold shift in IC 50 compared to MTAP + cells. Several structurally related derivatives of this compound also showed enhanced growth inhibition in MTAP – yeast. These compounds were also examined for growth inhibition of isogenic MTAP + and MTAP – HT1080 fibrosarcoma cells, and 4 of the 5 compounds exhibited evidence of modest but significant increased potency in MTAP – cells. In summary, these studies show the feasibility of differential growth screening technology and have identified a novel class of compounds that can preferentially inhibit growth of MTAP – cells.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S2472555222077322; http://dx.doi.org/10.1177/1087057110386371; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=78951476128&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/21131597; https://linkinghub.elsevier.com/retrieve/pii/S2472555222077322; http://jbx.sagepub.com/cgi/doi/10.1177/1087057110386371; http://jbx.sagepub.com/content/16/1/44
Elsevier BV
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