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epigenetics compound library l1200  (Topscience Co Ltd)
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Topscience Co Ltd epigenetics compound library l1200
<t>Epigenetic</t> compound library screen identifies DNMT inhibitors as synthetic lethal drugs in PBRM1-deficient renal cancer cells. (A) Western Blot analysis showing loss of PBRM1 expression in the three PBRM1−/− clones. (B) The genomic Sanger sequencing of PBRM1 locus in 786-O PBRM1+/+ and PBRM1-/-(#1) cells. PBRM1−/− clone#1 lost 25 nucleotides in exon 3. (C) A compound inhibition rate plot of the first round screen data are shown. (D) A log10-IC50 plot of the second round screen data are shown. The IC50 values of the compounds against 786-O PBRM1+/+ and PBRM1-/- cells was plotted. Compounds with selectivity index (SI) > 2 for PBRM1−/− cells were chosen as synthetic lethality candidates. (E–H) Cell viability assay was done to certify the synthetic lethality effect by Fdcyd in 786-O isogenic pairs (E) and CAKI-1 isogenic pairs (F) . The other two DNMTis 5-Azacytidine (G) and Decitabine (H) were also used to test the IC50 in 786-O isogenic pairs. Error bars represent s.d. (n = 9) from three independent experiments. ANOVA P value of <0.001 for Fdcyd, 5-Azacytidine and Decitabine.
Epigenetics Compound Library L1200, supplied by Topscience Co Ltd, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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Epigenetic compound library screen identifies DNMT inhibitors as synthetic lethal drugs in PBRM1-deficient renal cancer cells. (A) Western Blot analysis showing loss of PBRM1 expression in the three PBRM1−/− clones. (B) The genomic Sanger sequencing of PBRM1 locus in 786-O PBRM1+/+ and PBRM1-/-(#1) cells. PBRM1−/− clone#1 lost 25 nucleotides in exon 3. (C) A compound inhibition rate plot of the first round screen data are shown. (D) A log10-IC50 plot of the second round screen data are shown. The IC50 values of the compounds against 786-O PBRM1+/+ and PBRM1-/- cells was plotted. Compounds with selectivity index (SI) > 2 for PBRM1−/− cells were chosen as synthetic lethality candidates. (E–H) Cell viability assay was done to certify the synthetic lethality effect by Fdcyd in 786-O isogenic pairs (E) and CAKI-1 isogenic pairs (F) . The other two DNMTis 5-Azacytidine (G) and Decitabine (H) were also used to test the IC50 in 786-O isogenic pairs. Error bars represent s.d. (n = 9) from three independent experiments. ANOVA P value of <0.001 for Fdcyd, 5-Azacytidine and Decitabine.

Journal: Frontiers in Oncology

Article Title: PBRM1 Deficiency Sensitizes Renal Cancer Cells to DNMT Inhibitor 5-Fluoro-2’-Deoxycytidine

doi: 10.3389/fonc.2022.870229

Figure Lengend Snippet: Epigenetic compound library screen identifies DNMT inhibitors as synthetic lethal drugs in PBRM1-deficient renal cancer cells. (A) Western Blot analysis showing loss of PBRM1 expression in the three PBRM1−/− clones. (B) The genomic Sanger sequencing of PBRM1 locus in 786-O PBRM1+/+ and PBRM1-/-(#1) cells. PBRM1−/− clone#1 lost 25 nucleotides in exon 3. (C) A compound inhibition rate plot of the first round screen data are shown. (D) A log10-IC50 plot of the second round screen data are shown. The IC50 values of the compounds against 786-O PBRM1+/+ and PBRM1-/- cells was plotted. Compounds with selectivity index (SI) > 2 for PBRM1−/− cells were chosen as synthetic lethality candidates. (E–H) Cell viability assay was done to certify the synthetic lethality effect by Fdcyd in 786-O isogenic pairs (E) and CAKI-1 isogenic pairs (F) . The other two DNMTis 5-Azacytidine (G) and Decitabine (H) were also used to test the IC50 in 786-O isogenic pairs. Error bars represent s.d. (n = 9) from three independent experiments. ANOVA P value of <0.001 for Fdcyd, 5-Azacytidine and Decitabine.

Article Snippet: Epigenetics Compound Library (L1200, 773 epigenetics compounds) was purchased from Topscience.

Techniques: Drug discovery, Western Blot, Expressing, Clone Assay, Sequencing, Inhibition, Viability Assay