Delving into the Latest Updates on Neornat, Inc. with Synapse

概览

疾病领域	数量

肿瘤	6
内分泌与代谢疾病	1

排名前五的药物类型	数量

miRNA	6

排名前五的靶点	数量

THBS1(血小板1)	2
microRNA let-7i-5p	1
IRAK1(白细胞介素-1受体相关激酶-1)	1

关联

6

项与 Neornat, Inc. 相关的药物

NRT-YHD_002

靶点

THBS1

作用机制

THBS1调节剂

在研机构

Neornat, Inc.

原研机构

Neornat, Inc.

在研适应症

肺癌

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期-

NRT-NMJ_002

靶点-

作用机制-

在研机构

Neornat, Inc.

原研机构

Neornat, Inc.

在研适应症

实体瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期-

NRT-NMJ_001

靶点-

作用机制-

在研机构

Neornat, Inc.

原研机构

Neornat, Inc.

在研适应症

肝细胞癌

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期-

100 项与 Neornat, Inc. 相关的临床结果

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0 项与 Neornat, Inc. 相关的专利（医药）

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6

项与 Neornat, Inc. 相关的文献（医药）

2024-03-01·Anticancer Research

Co-treatment With Aripiprazole and Vincristine Sensitizes P-Glycoprotein-Overexpressing Drug-resistant MCF-7/ADR Breast Cancer Cells

Article

作者: Yoon, Sungpil ; Kim, Hyung Sik ; Shin, Joo Kyung

BACKGROUND/AIMEvidence supports that use of aripiprazole sensitizes drug-resistant oral cancer cells. The aim of the study was to investigate whether aripiprazole can achieve sensitization of highly drug-resistant breast cancer cells, as well as identify its relevant mechanisms of action.MATERIALS AND METHODSMCF-7/ADR, KB, and KBV20C breast cancer cells were treated with aripiprazole, vincristine (VIC), vinorelbine, vinblastine and their combination. Cell viability assay, annexin V analyses, cellular morphology and density observation with a microscope, western-blotting, fluorescence-activated cell sorting (FACS), and analysis for P-gp inhibitory activity were performed to investigate the drugs' mechanism of action.RESULTSWe found that high drug resistance in MCF-7/ADR cells results from high P-gp inhibitory activity via overexpression of P-gp. Aripiprazole reduced cell viability, increased G₂ arrest, and upregulated apoptosis when used as a co-treatment with VIC. Furthermore, we demonstrated that co-treatment with vinorelbine and vinblastine increased the sensitization of MCF-7/ADR breast cancer cells to aripiprazole. We confirmed that VIC-aripiprazole combination has much higher sensitization effects than either VIC-thioridazine or VIC-trifluoperazine co-treatment in MCF-7/ADR cells, since the previously known bipolar drugs (thioridazine and trifluoperazine) has lower P-gp inhibitory activity. However, aripiprazole-induced sensitization was not observed in VIC-treated MDA-MB-231 breast cancer cells suggesting that combination therapy with aripiprazole is specific for P-gp-overexpressing drug-resistant breast cancer cells.CONCLUSIONCo-treatment with low doses of aripiprazole sensitized MCF-7/ADR cells to VIC. Combination therapy with aripiprazole may be a valuable tool for delaying or reducing cancer recurrence by targeting P-gp-overexpressing drug-resistant breast cancer cells.

2021-07-15·Oncogene1区 · 医学

SMARCA4 oncogenic potential via IRAK1 enhancer to activate Gankyrin and AKR1B10 in liver cancer

1区 · 医学

Article

作者: Jeong, Seung Min ; Kim, Sang Yean ; Shen, Qingyu ; Nam, Suk Woo ; Park, Won Sang ; Yu, Kyung-Rok ; Na, Min Jeong ; Kim, Hyung Seok ; Shin, Eunbi ; Yang, Hee Doo ; Son, Keunhong ; Ahn, Young Min ; Kang, Keunsoo ; Lee, Eun Kyung ; You, Jueng Soo ; Yu, Suji

SWItch/Sucrose Non-Fermentable (SWI/SNF) is a multiprotein complex essential for the regulation of eukaryotic gene expression. SWI/SNF complex genes are genetically altered in over 20% of human malignancies, but the aberrant regulation of the SWI/SNF subunit genes and subsequent dysfunction caused by abnormal expression of subunit gene in cancer, remain poorly understood. Among the SWI/SNF subunit genes, SMARCA4, SMARCC1, and SMARCA2 were identified to be overexpressed in human hepatocellular carcinoma (HCC). Modulation of SMARCA4, SMARCC1, and SMARCA2 inhibited in vitro tumorigenesis of HCC cells. However, SMARCA4-targeting elicited remarkable inhibition in an in vivo Ras-transgenic mouse HCC model (Ras-Tg), and high expression levels of SMARCA4 significantly associated with poor prognosis in HCC patients. Furthermore, most HCC patients (72-86%) showed SMARCA4 overexpression compared to healthy controls. To identify SMARCA4-specific active enhancers, mapping, and analysis of chromatin state in liver cancer cells were performed. Integrative analysis of SMARCA4-regulated genes and active chromatin enhancers suggested 37 genes that are strongly activated by SMARCA4 in HCC. Through chromatin immunoprecipitation-qPCR and luciferase assays, we demonstrated that SMARCA4 activates Interleukin-1 receptor-associated kinase 1 (IRAK1) expression through IRAK1 active enhancer in HCC. We then showed that transcriptional activation of IRAK1 induces oncoprotein Gankyrin and aldo-keto reductase family 1 member B10 (AKR1B10) in HCC. The regulatory mechanism of the SMARCA4-IRAK1-Gankyrin, AKR1B10 axis was further demonstrated in HCC cells and in vivo Ras-Tg mice. Our results suggest that aberrant overexpression of SMARCA4 causes SWI/SNF to promote IRAK1 enhancer to activate oncoprotein Gankyrin and AKR1B10, thereby contributing to hepatocarcinogenesis.

ADAR1-dependent miR-3144-3p editing simultaneously induces MSI2 and suppresses SLC38A4 in liver cancer

作者: Ha, Jin Woong ; Jeon, Soyoung ; Nam, Suk Woo ; Yang, Hee Doo ; Shin, Eunbi ; Park, Won Sang ; Na, Min Jeong ; Kang, Keunsoo ; Moon, Kiho ; Kim, Sang Yean ; Kim, Hyung Seok ; Son, Keun Hong

AbstractAberrant adenosine-to-inosine (A-to-I) RNA editing, catalyzed by adenosine deaminase acting on double-stranded RNA (ADAR), is implicated in various cancers, but the mechanisms by which microRNA (miRNA) editing contributes to cancer development are currently largely unknown. Our multi-step hepatocellular carcinogenesis transcriptome data analyses, together with publicly available data, indicated that ADAR1 is the most dysregulated gene among the RNA editing enzyme families in liver cancer. Targeted inactivation of ADAR1 inhibits in vitro tumorigenesis of liver cancer cells. Integrative computational analyses of RNA editing hotspots and the editing frequency of miRNAs suggested miR-3144-3p a potential mRNA edited by ADAR1 in liver cancer progression. ADAR1 promoted A-to-I editing of the canonical miR-3144-3p to change position 3 adenosine in the seed region to guanine (ED_miR-3144-3p(3_A < G)) in liver cancer cells. We then demonstrated that Musashi RNA-binding protein 2 (MSI2) is a specific target of miR-3144-3p, and that MSI2 overexpression is due to ADAR1-dependent over-editing of the canonical miR-3144-3p in liver cancer. In addition, target prediction analyses and validation experiments identified solute carrier family 38 member 4 (SLC38A4) as specific target gene for ED_miR-3144-3p(3_A < G). Ectopic expressions of both ADAR1 and ED_miR-3144-3p(3_A < G) mimics enhanced mitotic activities and that ADAR1 suppressed SLC38A4 in liver cancer cells. Treatments with mouse-specific ADAR1-, MSI2-siRNA or SLC39A4-expressing plasmids suppressed tumor incidence and growth in a spontaneous mouse liver cancer model. Our findings suggest that aberrant regulation of ADAR1 augments oncogenic MSI2 via overediting the canonical miR-3144-3p, and the resultant ED_miR-3144-3p(3_A < G) simultaneously suppresses tumor suppressor SLC38A4, thereby contributing to hepatocellular carcinogenesis.

100 项与 Neornat, Inc. 相关的药物交易

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100 项与 Neornat, Inc. 相关的转化医学

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药物发现

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当前项目

药物(靶点)	适应症	全球最高研发状态

NRT-YHD_003 ( THBS1 )	胰腺癌更多	药物发现
NRT-NMJ_001	肝细胞癌更多	药物发现
NRT-YHD_002 ( THBS1 )	肺癌更多	药物发现
NRT-KSY_001 ( IRAK1 )	肝细胞癌更多	药物发现
NRT-NMJ_002	实体瘤更多	药物发现