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LSD1 pharmacological inhibition in SET-2 containing wild type and mutant LSD1

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE121426 | GEO | 2019/01/23

REPOSITORIES: GEO

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LSD1 pharmacological inhibition in SET-2 containing wild type and mutant LSD1 [RNA-Seq]

Project description:We characterized the effect of GSK-LSD1 treatment on gene expression for both wt SET-2 and drug-resistant SET-2 LSD1 (Leu659_Asn660insArg)

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LSD1 pharmacological inhibition in SET-2 containing wild type and mutant LSD1 [ChIP-Seq]

Project description:We characterized the changes in histone modifications as well as the localization of LSD1 and GFI1B for both wt SET-2 and drug-resistant SET-2 LSD1 (Leu659_Asn660insArg) treated with GSK-LSD1

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LSD1 pharmacological inhibition in SET-2 containing wild type and mutant LSD1

Project description:LSD1 pharmacological inhibition in SET-2 containing wild type and mutant LSD1

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LSD1 pharmacological inhibition in SET-2 containing wild type and mutant LSD1 [ChIP-Seq]

Project description:LSD1 pharmacological inhibition in SET-2 containing wild type and mutant LSD1 [ChIP-Seq]

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LSD1 pharmacological inhibition in SET-2 containing wild type and mutant LSD1 [RNA-Seq]

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Pharmacological LSD1 inhibition in MCC

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-09-04 | GSE147817 | GEO

Pharmacological Inhibition of LSD1 for Cancer Treatment.

Project description:Lysine-specific demethylase 1A (LSD1, also named KDM1A) is a demethylase that can remove methyl groups from histones H3K4me1/2 and H3K9me1/2. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, and is associated with inferior prognosis. Pharmacological inhibition of LSD1 has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. This review will present the structural aspects of LSD1, its role in carcinogenesis, a comparison of currently available approaches for screening LSD1 inhibitors, a classification of LSD1 inhibitors, and its potential as a drug target in cancer therapy.

| S-EPMC6320820 | biostudies-literature

Impact of genetic depletion or pharmacological inhibition of LSD1 on gene expression in ovarian cancer cells

Project description:This SuperSeries is composed of the SubSeries listed below.

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Pharmacological LSD1 inhibition in MCC

Project description:Pharmacological LSD1 inhibition in MCC

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Pharmacological inhibition of LSD1 for the treatment of MLL-rearranged leukemia.

Project description:BACKGROUND:Mixed lineage leukemia (MLL) gene translocations are found in ~75% infant and 10% adult acute leukemia, showing a poor prognosis. Lysine-specific demethylase 1 (LSD1) has recently been implicated to be a drug target for this subtype of leukemia. More studies using potent LSD1 inhibitors against MLL-rearranged leukemia are needed. METHODS:LSD1 inhibitors were examined for their biochemical and biological activities against LSD1 and MLL-rearranged leukemia as well as other cancer cells. RESULTS:Potent LSD1 inhibitors with biochemical IC50 values of 9.8-77 nM were found to strongly inhibit proliferation of MLL-rearranged leukemia cells with EC50 of 10-320 nM, while these compounds are generally non-cytotoxic to several other tumor cells. LSD1 inhibition increased histone H3 lysine 4 (H3K4) methylation, downregulated expression of several leukemia-relevant genes, induced apoptosis and differentiation, and inhibited self-renewal of stem-like leukemia cells. Moreover, LSD1 inhibitors worked synergistically with inhibition of DOT1L, a histone H3 lysine 79 (H3K79) methyltransferase, against MLL-rearranged leukemia. The most potent LSD1 inhibitor showed significant in vivo activity in a systemic mouse model of MLL-rearranged leukemia without overt toxicities. Mechanistically, LSD1 inhibitors caused significant upregulation of several pathways that promote hematopoietic differentiation and apoptosis. CONCLUSIONS:LSD1 is a drug target for MLL-rearranged leukemia, and LSD1 inhibitors are potential therapeutics for the malignancy.

| S-EPMC4789278 | biostudies-literature

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