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

作用方式

抑制剂

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.

权益机构-

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/序列

分子式C20H23N3O7

InChIKeyJNZBHHQBPHSOMU-WNQIDUERSA-N

CAS号618863-54-0

关联

4

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.

NCT00715637

/ Unknown status临床3期

Phase III 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)- The ACCEDE Study

Amonafide is a DNA intercalating agent and inhibitor of topoisomerase II that has been extensively studied in patients with malignant solid tumors. Amonafide has also been studied in patients with AML.
The purpose of this study is to assess the relative efficacy and safety of amonafide in combination with cytarabine compared to daunorubicin with cytarabine in subjects with documented secondary AML.

开始日期2007-06-01

申办/合作机构

Antisoma Research Ltd.

NCT00087854

/ Completed临床1/2期

Dose-Defining Study of a NAT2 Phenotype-Based Dosing Regimen of Intravenous Amonafide L-Malate Administered Weekly in Men With Androgen-Independent Prostate Cancer (AIPC)

The purpose of this study is to assess the safety and efficacy of Amonafide in men with androgen-independent prostate cancer, assigned to individualized doses of Amonafide based on acetylator phenotype information (doses adjusted on individual metabolism).

开始日期2004-03-01

申办/合作机构

Antisoma, Inc.

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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316

项与氨萘非特马来酸盐相关的文献（医药）

2025-02-17·ACS Applied Bio Materials

Deciphering Binding Potential of Naphthalimide–Coumarin Conjugate with c-MYC G-Quadruplex for Developing Anticancer Agents: A Spectroscopic and Molecular Modeling Approach

Article

作者: Paul, Kamaldeep ; Gupta, Saurabh ; Luxami, Vijay

It has been well accumulated that G-quadruplex (G4-DNA) has great anticancer relevance, and various heterocyclic moieties have been synthesized and examined as potent G4-DNA binders with promising anticancer activity. Here, we have synthesized a series of naphthalimide-triazole-coumarin conjugates by substituting various amines and further examine their anticancer activity against 60 human cancer cell lines at 10 μM. One and five dose concentration results reveal low values of MG-MID GI₅₀ for compounds including 8a (3.18 μM), 8b (13.11 μM), 8e (7.68 μM) and 8f (1.75 μM). Further cell apoptosis manifests that all compounds can induce cell apoptosis in cancer cells by stabilizing the c-MYC promoter G-quadruplex. Therefore, the G-quadruplex-mediated pathway may be responsible for the apoptosis that these naphthalimide-coumarin compounds caused in cancer cells. Therefore, multispectroscopic techniques are employed to evaluate the binding of molecules with c-MYC G4-DNA where all four molecules readily bind to G4-DNA and stabilize it with a high binding constant, leading to inhibition of cancer cells and apoptosis of cancer cells. Binding studies toward ct-DNA disclose that these compounds do not interact with ds-DNA and thus selectively target G4-DNA to exert their anticancer activity. All the active compounds have greater affinity toward Human Serum Albumin (HSA) and can readily bind with HSA with a binding constant of 12 × 10⁴ M^-1 (8a), 13.0 × 10⁴ M^-1 (8b), 14.2 × 10⁴ M^-1 (8e), 16.3 × 10⁴ M^-1 (8f). Thus, the results disclose that inhibition and killing of cancer cells by these derivatives feasibly occur due to their ability to interact with c-MYC G-quadruplex forming promoters and their high affinity toward HSA unfold potent anticancer agents and can be taken further for clinical trials.

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.

2024-12-01·Biochemical Genetics

Comprehensive Analysis of the SUMO-related Signature: Implication for Diagnosis, Prognosis, and Immune Therapeutic Approaches in Cervical Cancer

Article

作者: Li, Xiuting ; Zhang, Xing ; Zhang, Yan ; Cao, Jian ; Liu, Haohan ; Lin, Ning ; Ding, Bo ; Liu, Fengying ; Nie, Yamei ; Wang, Shizhi ; Hu, Jing ; Yan, Wenjing ; Chen, Xue

SUMOylation, an important post-translational protein modification, plays a critical role in cancer development and immune processes. This study aimed to construct diagnostic and prognostic models for cervical cancer (CC) using SUMOylation-related genes (SRGs) and explore their implications for novel clinical therapies. We analyzed the expression profiles of SRGs in CC patients and identified 15 SRGs associated with CC occurrence. After the subsequent qPCR verification of 20 cases of cancer and adjacent tissues, 13 of the 15 SRGs were differentially expressed in cancer tissues. Additionally, we identified molecular markers associated with the prognosis and recurrence of CC patients, based on SRGs. Next, a SUMOScore, based on SRG expression patterns, was generated to stratify patients into different subgroups. The SUMOScore showed significant associations with the tumor microenvironment, immune function features, immune checkpoint expression, and immune evasion score in CC patients, highlighting the strong connection between SUMOylation factors and immune processes. In terms of immune therapy, our analysis identified specific chemotherapy drugs with higher sensitivity in the subgroups characterized by high and low SUMOScore, indicating potential treatment options. Furthermore, we conducted drug sensitivity analysis to evaluate the response of different patient subgroups to conventional chemotherapy drugs. Our findings revealed enrichment of immune-related pathways in the low-risk subgroup identified by the prognostic model. In conclusion, this study presents diagnostic and prognostic models based on SRGs, accompanied by a comprehensive index derived from SRGs expression patterns. These findings offer valuable insights for CC diagnosis, prognosis, treatment, and immune-related analysis.

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	阿根廷	Antisoma Research Ltd.	2007-06-01
急性髓性白血病	临床3期	德国	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	意大利	Antisoma Research Ltd.	2007-06-01
急性髓性白血病	临床3期	法国	Antisoma Research Ltd.	2007-06-01
急性髓性白血病	临床3期	以色列	Antisoma Research Ltd.	2007-06-01
急性髓性白血病	临床3期	比利时	Antisoma Research Ltd.	2007-06-01
急性髓性白血病	临床3期	加拿大	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	厄瓜多尔	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 \| J Clin Oncol) 人工标引	临床3期	急性髓性白血病一线	433	cytarabine+amonafide	(憲獵夢蓋獵淵廠糧積築) = 簾構繭鏇襯範積窪憲顧製蓋顧願蓋網範艱願夢 (蓋觸餘鑰蓋願鑰鬱選窪 ) 更多	不佳	2015-04-10
NCT00715637 (Pubmed \| J Urol \| J Clin Oncol) 人工标引	临床3期	急性髓性白血病一线	433	daunorubicin+cytarabine	(憲獵夢蓋獵淵廠糧積築) = 獵鏇蓋遞構鏇鹽選餘網製蓋顧願蓋網範艱願夢 (蓋觸餘鑰蓋願鑰鬱選窪 ) 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 cytarabine	鑰範艱窪觸蓋窪衊衊鬱(窪獵繭齋積廠餘簾遞範) = 衊遞築壓淵壓窪積壓淵壓遞簾觸齋淵簾遞網醖 (積網觸夢鹹繭鏇範廠製 )	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	鑰範艱窪觸蓋窪衊衊鬱(窪獵繭齋積廠餘簾遞範) = 鹹壓範膚膚製蓋憲窪繭壓遞簾觸齋淵簾遞網醖 (積網觸夢鹹繭鏇範廠製 )	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)	(鏇鬱鑰繭艱襯憲觸鹹窪) = 艱積積簾製製廠艱膚鏇製醖鬱糧窪獵鏇憲鏇醖 (糧鹹鏇鬱獵顧築膚壓齋 ) 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)	(鏇鬱鑰繭艱襯憲觸鹹窪) = 製衊蓋膚憲獵遞網糧簾製醖鬱糧窪獵鏇憲鏇醖 (糧鹹鏇鬱獵顧築膚壓齋 ) 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	(餘簾襯夢積鏇壓鬱齋繭) = 蓋願遞艱鹹繭鹹積憲壓鹹糧廠積艱窪蓋夢壓積 (鬱鬱觸繭膚選築壓構顧 ) 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	(製鏇齋餘淵衊製衊壓夢) = 積蓋願窪網鬱鹽繭鏇憲鬱範網獵積繭夢構鏇願 (鬱壓糧遞齋顧淵鬱製積 ) 更多	-	2007-06-20
ASCO2006	临床1期	急性髓性白血病	20	Amonafide	餘觸醖憲鑰餘夢範衊構(觸繭衊壓築夢鑰衊憲齋) = 廠淵鏇窪糧獵簾衊顧膚願範簾襯窪繭選鑰鑰衊 (鏇鏇淵觸鏇築構遞製觸 ) 更多	-	2006-06-20
ASCO2005	临床1期	急性髓性白血病	26	Amonafide + Cytosine Arabinoside (AraC)	(壓築構憲窪襯艱衊遞築) = 構憲壓齋餘夢鑰壓簾齋製鏇簾鬱構餘範顧鏇壓 (襯鏇衊鹽餘鹽憲構艱製 ) 更多	-	2005-06-01