氨萘非特马来酸盐(Amonafide Maleate) - 药物靶点：DNA x Top II_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Amonafide L-Malate(USAN)

+ [5]

靶点

DNA x Top II

作用机制

DNA抑制剂(DNA抑制剂)、Top II抑制剂(拓扑异构酶II抑制剂)

治疗领域

肿瘤血液及淋巴系统疾病泌尿生殖系统疾病

在研适应症-

非在研适应症

急性髓性白血病去势抵抗性前列腺癌

原研机构

Antisoma, Inc.

在研机构-

非在研机构

Antisoma Research Ltd.

Antisoma, Inc.

最高研发阶段无进展临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C20H23N3O7

InChIKeyJNZBHHQBPHSOMU-WNQIDUERSA-N

CAS号618863-54-0

关联

6

项与氨萘非特马来酸盐相关的临床试验

NCT01066494 / Unknown status临床2期

A Phase IIa Pharmacokinetic and Efficacy Study of Amonafide L-malate (AS1413) in Combination With Cytarabine in Adult Patients With Acute Myeloid Leukemia (AML)

A phase IIa study to evaluate the pharmacokinetic and efficacy of amonafide L-malate (AS1413) in combination with cytarabine in treating patients with acute myeloid leukemia (AML)

开始日期2010-01-01

申办/合作机构

Antisoma Research Ltd.

EUCTR2007-004427-38-GB / Not yet recruitingN/A

Phase 3 Open-Label Randomized Study of Amonafide L-Malate in Combination withCytarabine Compared to Daunorubicin in Combination with Cytarabine in Patients with Secondary Acute Myeloid Leukemia (AML) - ACCEDE

开始日期2009-07-17

申办/合作机构

Antisoma Research Ltd.

EUCTR2007-004427-38-IT / Not yet recruitingN/A

Phase 3 Open-Label Randomized Study of Amonafide L-Malate in Combination with Cytarabine Compared to Daunorubicin in Combination with Cytarabine in Patients with Secondary Acute Myeloid Leukemia (AML)

开始日期2009-02-09

申办/合作机构

Sarossa Capital Ltd.

100 项与氨萘非特马来酸盐相关的临床结果

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100 项与氨萘非特马来酸盐相关的转化医学

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100 项与氨萘非特马来酸盐相关的专利（医药）

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171

项与氨萘非特马来酸盐相关的文献（医药）

2024-12-01·International Immunopharmacology

Single-cell transcriptomics reveals tumor microenvironment changes and prognostic gene signatures in hepatocellular carcinoma

Article

作者: Li, Xiangqian ; Wu, Yilin ; Liang, Yong ; Xie, Tong ; Lu, Ying ; Ding, Zhilong ; Zhu, WeiJie ; Zhang, Cui ; Hu, Yihuai ; Zhong, Fei ; Ren, Shiying ; Zhai, Yangyang ; Wang, Shiyan ; Chen, Yunli

BACKGROUNDHepatocellular Carcinoma (HCC) is the most common type of primary liver cancer, accounting for the majority of liver cancer cases. Hepatocellular Carcinoma not only exhibits high heterogeneity but also possesses an immune-suppressive tumor microenvironment that promotes tumor evasion, posing substantial difficulties for efficient therapy. Our aim is to utilize single-cell RNA transcriptome data to investigate the dynamic changes in the tumor microenvironment during the malignant progression of HCC, the communication among immune cells, and the marker genes associated with patient prognosis.METHODSWe constructed expression matrices from open single-cell RNA transcriptome data (GSE149614) of HCC patients (representing stages I-IV), establishing single-cell RNA transcriptional atlases for different stages of HCC progression. For each stage, we conducted cell subgroup analysis to identify cell types at each stage. Horizontally, we explored the dynamic changes of the same cell type across different stages, performing trajectory analysis and prognosis analysis. Vertically, we investigated pairwise comparisons of different stages of HCC progression, probing the dynamic alterations in tumor microenvironment immune cell signaling pathways. Finally, potential drugs for the treatment of HCC were predicted based on relevant genes.FINDINGSAs the HCC advances towards increased malignancy, there is a shift in the predominant composition of the tumor microenvironment, with a decline in the dominance of hepatic cells. Tumor-infiltrating immune cells migrate and accumulate within the tumor microenvironment, where T cells and myeloid cells display distinct patterns of change. Genes associated with cancer-associated fibroblasts (CAFs) and T cells are correlated with adverse patient outcomes. In the late stages of HCC, the tumor microenvironment is infiltrated by more myeloid-derived suppressor cells (MDSCs), and a prognostic model constructed based on genes related to myeloid cells can predict patient outcomes. Additionally, in the analysis of transcription factors, YY1 and MYC are found to be highly expressed. Cell communication analysis among tumor-infiltrating immune cells reveals significant differences in the main signaling pathways at different stages of HCC progression. Finally, drug sensitivity analysis based on key genes identifies Acetalax, Allopurinol, and Amonafide as potential candidates for HCC treatment.

2024-09-01·Bioorganic Chemistry

Amonafide-based H2O2-responsive theranostic prodrugs: Exploring the correlation between H2O2 level and anticancer efficacy

Article

作者: Yuan, Ye ; Sun, Wenbin ; Yao, Xueyan ; Yin, Jian ; Fu, Junjie ; Hu, Jing

Leveraging the elevated hydrogen peroxide (H₂O₂) levels in cancer cells, H₂O₂-activated prodrugs have emerged as promising candidates for anticancer therapy. Notably, the efficacy of these prodrugs is influenced by the varying H₂O₂ levels across different cancer cell types. In this context, we have developed a novel H₂O₂-activated prodrug, PBE-AMF, which incorporates a phenylboronic ester (PBE) motif. Upon H₂O₂ exposure, PBE-AMF liberates the fluorescent and cytotoxic molecule amonafide (AMF), functioning as a theranostic agent. Our studies with PBE-AMF have demonstrated a positive correlation between intracellular H₂O₂ concentration and anticancer activity. The breast cancer cell line MDA-MB-231, characterized by high H₂O₂ content, showed the greatest susceptibility to this prodrug. Subsequently, we replaced the PBE structure with phenylboronic acid (PBA) to obtain the prodrug PBA-AMF, which exhibited enhanced stability, aqueous solubility, and tumor cell selectivity. This selectivity is attributed to its affinity for sialic acid, which is overexpressed on the surfaces of cancer cells. In vitro assays confirmed that PBA-AMF potently and selectively inhibited the proliferation of MDA-MB-231 cells, while sparing non-cancerous MCF-10A cells. Mechanistic investigations indicated that PBA-AMF impedes tumor proliferation by inhibiting DNA synthesis, reducing ATP levels, inducing apoptosis, and arresting the cell cycle. Our work broadens the range of small molecule H₂O₂-activated anticancer theranostic prodrugs, which are currently limited in number. We anticipate that the applications of PBA-AMF will extend to a wider spectrum of tumors and other diseases associated with increased H₂O₂ levels, thereby offering new horizons in cancer diagnostics and treatment.

2024-03-01·Bioorganic Chemistry

Rational design and synthesis of triazene-amonafide derivatives as novel potential antitumor agents causing oxidative damage towards DNA through intercalation mode

Article

作者: Gao, Yun-Fei ; Xia, Ya-Mu ; Sun, Ping ; Zhang, Xue ; Zhang, Jia-Yin ; Gao, Wei-Wei ; Yu, Ri-Lei ; Liang, Chen ; Xu, Na ; Zhang, Qi-Ming

In this work, we rationally designed and synthesized two novel triazene-amonafide derivatives 2-(2-(diisopropylamino)ethyl)-5-(3,3-dimethyltriaz-1-en-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (D-11) and 5-(3,3-diethyltriaz-1-en-1-yl)-2-(2-(diisopropylamino)ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (D-12) as potential antitumor agents. The DNA damage induced by the intercalation mode of D-11 (D-12) towards DNA was electrochemically detected through the construction of efficient biosensors. The consecutive processes of reversible redox of naphthylimide ring and irreversible oxidation of triazene moiety were elucidated on the surface of glassy carbon electrode (GCE) by CV, SWV, and DPV methods. Electrochemical biosensors were obtained through the immobilization of ctDNA, G-quadruplexes, poly(dG), and poly(dA), respectively, on the clean surface of GCE. After the incubation of biosensors with D-11 or D-12, the peaks of dGuo and dAdo decreased prominently, and the peak of 8-oxoGua appeared at +0.50 V, suggesting that the interaction between D-11 (D-12) and DNA could result in the oxidative damage of guanine. Unexpected, the as-prepared DNA biosensor possessed satisfactory anti-interference property and good practicability in real samples. UV-vis and fluorescence spectra, and gel electrophoresis assays were employed to further confirm the intercalation mode of D-11 (D-12) towards DNA base pairs. Moreover, D-11 was proved to exhibit stronger anti-proliferation activity than mitionafide and amonafide against both A549 and HeLa cell lines.

100 项与氨萘非特马来酸盐相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	氨萘非特马来酸盐	-	DB05022

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
急性髓性白血病	临床3期	意大利	Antisoma Research Ltd.	2007-06-01
急性髓性白血病	临床3期	波兰	Antisoma Research Ltd.	2007-06-01
急性髓性白血病	临床3期	匈牙利	Antisoma Research Ltd.	2007-06-01
急性髓性白血病	临床3期	捷克	Antisoma Research Ltd.	2007-06-01
急性髓性白血病	临床3期	英国	Antisoma Research Ltd.	2007-06-01
急性髓性白血病	临床3期	阿根廷	Antisoma Research Ltd.	2007-06-01
急性髓性白血病	临床3期	美国	Antisoma Research Ltd.	2007-06-01
急性髓性白血病	临床3期	智利	Antisoma Research Ltd.	2007-06-01
急性髓性白血病	临床3期	澳大利亚	Antisoma Research Ltd.	2007-06-01
急性髓性白血病	临床3期	韩国	Antisoma Research Ltd.	2007-06-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00715637 (Pubmed \| J Urol) 人工标引	临床3期	急性髓性白血病一线	433	cytarabine+amonafide	(鏇願範觸觸繭鏇鬱顧鑰) = 網願繭廠憲醖廠蓋遞積遞齋齋築製鑰築鏇醖糧 (壓遞壓獵餘築鹽鏇鹽鹽 ) 更多	不佳	2015-04-10
NCT00715637 (Pubmed \| J Urol) 人工标引	临床3期	急性髓性白血病一线	433	daunorubicin+cytarabine	(鏇願範觸觸繭鏇鬱顧鑰) = 夢窪夢鏇製淵構鏇鹽網遞齋齋築製鑰築鏇醖糧 (壓遞壓獵餘築鹽鏇鹽鹽 ) 更多	不佳	2015-04-10
ACCEDE (ASCO2011)	临床3期	复发性急性髓细胞白血病	433	AS1413 plus cytarabineAS1413 plus cytarabine	醖構齋蓋願繭範觸壓鹽(網觸衊餘繭膚築糧襯醖) = 醖選淵鹽積觸築顧艱顧願艱夢築構選膚壓網願 (簾簾鹹醖鑰選醖膚鏇選 )	不佳	2011-05-20
ACCEDE (ASCO2011)	临床3期	复发性急性髓细胞白血病	433	Daunorubicin plus cytarabine	醖構齋蓋願繭範觸壓鹽(網觸衊餘繭膚築糧襯醖) = 網網艱積壓鹹糧簾網襯願艱夢築構選膚壓網願 (簾簾鹹醖鑰選醖膚鏇選 )	不佳	2011-05-20
ASCO2010	N/A	急性髓性白血病 \| 治疗相关性急性髓系白血病	88	amonafide (tAML)	(夢餘遞窪鬱淵願憲願遞) = 積鬱範齋襯顧願選醖鑰衊築鑰淵願襯窪齋糧蓋 (淵構繭鹹襯糧構醖網製 ) 更多	-	2010-05-20
ASCO2010	N/A	急性髓性白血病 \| 治疗相关性急性髓系白血病	88	amonafide (MDS→AML)	(夢餘遞窪鬱淵願憲願遞) = 積廠壓窪製憲範膚餘顧衊築鑰淵願襯窪齋糧蓋 (淵構繭鹹襯糧構醖網製 ) 更多	-	2010-05-20
ASCO2008	临床2期	急性髓性白血病	88	Amonafide 600 mg/m2 + ara-C 200 mg/m2	(醖廠壓範鹹範積糧網鹽) = 獵範淵鑰獵構醖窪繭鬱糧觸醖積壓膚膚憲憲蓋 (鹹壓齋獵鹹製遞遞築積 ) 更多	-	2008-05-20
ASCO2007	临床2期	急性髓性白血病	80	Amonafide 600 mg/m2/day + CIV ara-C 200 mg/m2/day	(齋壓餘襯窪壓觸艱廠製) = 築艱憲獵範鏇繭窪顧鹽夢遞選壓夢壓選簾獵顧 (鹹鑰鹹齋鹹衊淵鏇網淵 ) 更多	-	2007-06-20
ASCO2006	临床1期	急性髓性白血病	20	Amonafide	獵艱鹽鏇衊夢壓蓋壓觸(鏇廠製餘觸繭鬱夢壓築) = 製構簾範廠選鑰鏇艱遞簾襯選齋憲醖構顧範廠 (遞範鹽淵蓋遞鏇鑰鹹選 ) 更多	-	2006-06-20
ASCO2005	临床1期	急性髓性白血病	26	Amonafide + Cytosine Arabinoside (AraC)	(壓鏇鹽網顧鑰願廠壓觸) = 鬱鑰鬱襯鑰鬱範艱蓋積繭築構築簾鹹窪餘窪範 (築積夢鬱膚鏇築夢鏇鏇 ) 更多	-	2005-06-01