Nonpeptidic Propargylamines as Inhibitors of Lysine Specific Demethylase 1 (LSD1) with Cellular Activity

Lysine demethylases play an important role in epigenetic regulation and thus in the development of diseases like cancer or neurodegenerative disorders. As the lysine specific demethylase 1 (LSD1/KDM1) has been strongly connected to androgen and estrogen dependent gene expression, it serves as a promising target for the therapy of hormone dependent cancer. Here, we report on the discovery of new small molecule inhibitors of LSD1 containing a propargylamine warhead, starting out from lysine containing substrate analogues. On the basis of these substrate mimicking inhibitors, we were able to increase potency by a combination of similarity-based virtual screening and subsequent synthetic optimization resulting in more druglike LSD1 inhibitors that led to histone hypermethylation in breast cancer cells

IBLI calculation sheet

This note explains how to derive total value of insured livestock, insurance premium and indemnity payment

Additional file 5: of Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes

Figure S3. ChromHMM model of 15 chromtain states defined by all 8 histone modifications. (PDF 358 kb

Additional file 10: of Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes

Table S7. Subtype gene signatures of active transcription states and active transcription flanking states. (XLSX 23 kb

Additional file 7: of Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes

Table S5. List of genes with subtype specific active enhancer states. (XLS 212 kb

Additional file 15: of Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes

Figure S7. Chromatin state landscape of depleted H3K27me3 signals at NLRP gene cluster in normal-like celllines. (PDF 595 kb

Additional file 11: of Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes

Table S8. Significant pathways of subtype gene signatures of active transcription states and active transcription flanking states. (XLSX 18 kb

Additional file 3: of Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes

Table S2. ChIP-seq sample replicates correlation. (XLSX 61 kb

Additional file 14: of Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes

Table S6. List of genes with subtype specific repressive polycomb domain states. (XLS 10 kb

Additional file 8: of Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes

Figure S5. Spearman correlation of H3K36me3 occupancy and gene expression levels in all samples. (PDF 489 kb