DDP-38003(DDP-38003) - 药物靶点：KDM1A_在研适应症：肿瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

KDM1A

作用机制

KDM1A抑制剂(赖氨酸特异性组蛋白脱甲基酶-1抑制剂)

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

Istituto Europeo di Oncologia SRL

在研机构

Istituto Europeo di Oncologia SRL

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C21H26N4O

InChIKeySSWIQIUOBLUKHT-VQTJNVASSA-N

CAS号1831167-97-5

关联

100 项与 DDP-38003 相关的临床结果

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100 项与 DDP-38003 相关的转化医学

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100 项与 DDP-38003 相关的专利（医药）

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1

项与 DDP-38003 相关的文献（医药）

2022-02-04·Oncogene1区 · 医学

Pharmacological inhibition of LSD1 triggers myeloid differentiation by targeting GSE1 oncogenic functions in AML

1区 · 医学

Article

作者: Ravasio, Roberto ; Pallavicini, Isabella ; Ceccacci, Elena ; Boffo, Francesca Ludovica ; Minucci, Saverio ; Nicosia, Luciano ; Bedin, Fabio ; Conforti, Fabio ; Somervaille, Tim C P ; Massignani, Enrico ; Bonaldi, Tiziana

AbstractThe histone demethylase LSD1 is over-expressed in hematological tumors and has emerged as a promising target for anticancer treatment, so that several LSD1 inhibitors are under development and testing, in preclinical and clinical settings. However, the complete understanding of their complex mechanism of action is still unreached. Here, we unraveled a novel mode of action of the LSD1 inhibitors MC2580 and DDP-38003, showing that they can induce differentiation of AML cells through the downregulation of the chromatin protein GSE1. Analysis of the phenotypic effects of GSE1 depletion in NB4 cells showed a strong decrease of cell viability in vitro and of tumor growth in vivo. Mechanistically, we found that a set of genes associated with immune response and cytokine-signaling pathways are upregulated by LSD1 inhibitors through GSE1-protein reduction and that LSD1 and GSE1 colocalize at promoters of a subset of these genes at the basal state, enforcing their transcriptional silencing. Moreover, we show that LSD1 inhibitors lead to the reduced binding of GSE1 to these promoters, activating transcriptional programs that trigger myeloid differentiation. Our study offers new insights into GSE1 as a novel therapeutic target for AML.

100 项与 DDP-38003 相关的药物交易

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