9-Aminocamptothecin(9-Aminocamptothecin) - 药物靶点：TOP1_专利_临床

概要

基本信息

药物类型

小分子化药

别名

9-Amino-20-S-camptothecin、Aminocamptothecin、NSC-629971 (racemic--isomer)

+ [5]

靶点

TOP1

作用机制

TOP1抑制剂(DNA拓扑异构酶I抑制剂)

治疗领域

肿瘤免疫系统疾病消化系统疾病+ [5]

在研适应症-

非在研适应症

晚期非小细胞肺癌晚期肾细胞癌皮肤T细胞淋巴瘤+ [11]

原研机构

Arisyn Therapeutics Inc

在研机构-

非在研机构

National Cancer Institute

Biogen, Inc.

Pfizer Inc.

+ [1]

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C20H17N3O4

InChIKeyFUXVKZWTXQUGMW-FQEVSTJZSA-N

CAS号91421-43-1

关联

6

项与 9-Aminocamptothecin 相关的临床试验

NCT00003192 / Completed临床2期IIT

A Phase II Trial of 9-Aminocamptothecin (NSC 603071) Administered as a 120-Hour Continuous Infusion in Patients With Previously Untreated Gastric Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
PURPOSE: Phase II trial to study the effectiveness of aminocamptothecin in treating patients with locally advanced, metastatic, or recurrent cancer of the stomach or esophagus.

开始日期1998-03-01

申办/合作机构

The University of Chicago

[+1]

NCT00002745 / Completed临床2期IIT

PHASE II STUDY OF 9-AMINOCAMPTOTHECIN (9-AC/DMA, NSC# 603071) IN PREVIOUSLY TREATED HODGKIN'S DISEASE AND NON-HODGKIN'S LYMPHOMA: IWF GRADES A-H

Phase II trial to study the effectiveness of aminocamptothecin in treating patients who have refractory or recurrent Hodgkin's disease or non-Hodgkin's lymphoma. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

开始日期1996-04-01

申办/合作机构

National Cancer Institute

NCT00002671 / Completed临床2期

PHASE II STUDY OF 9-20-S-AMINO-CAMPTOTHECIN (9-AC) AS SECOND LINE THERAPY IN ADVANCED OVARIAN CARCINOMA

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
PURPOSE: Phase II trial to study the effectiveness of aminocamptothecin in treating patients with recurrent or unresectable epithelial ovarian cancer that has been previously treated with platinum-based chemotherapy.

开始日期1995-12-01

申办/合作机构

NYU Langone Health

[+2]

100 项与 9-Aminocamptothecin 相关的临床结果

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100 项与 9-Aminocamptothecin 相关的转化医学

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100 项与 9-Aminocamptothecin 相关的专利（医药）

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293

项与 9-Aminocamptothecin 相关的文献（医药）

2024-09-01·International Journal of Biological Macromolecules

Development of a RNA-protein complex based smart drug delivery system for 9-hydroxycamptothecin

Article

作者: Shen, Xiao ; Wang, Yan ; Wang, Pingping ; Yan, Xing ; Li, Zhenhua ; Zhang, Tong ; Yang, Yi ; Zhou, Zhihua ; Xiong, Ying ; Tian, Ernuo

Camptothecin (CPT) is a monoterpenoid indole alkaloid with a wide spectrum of anticancer activity. However, its application is hindered by poor solubility, lack of targeting specificity, and severe side effects. Structural derivatization of CPT and the development of suitable drug delivery systems are potential strategies for addressing these issues. In this study, we discovered that the protein Cytochrome P450 Family 1 Subfamily A Member 1 (CYP1A1) from Homo sapiens catalyzes CPT to yield 9-hydroxycamptothecin (9-HCPT), which exhibits increased water solubility and cytotoxicity. We then created a RNA-protein complex based drug delivery system with enzyme and pH responsiveness and improved the targeting and stability of the nanomedicine through protein module assembly. The subcellular localization of nanoparticles can be visualized using fluorescent RNA probes. Our results not only identified the protein CYP1A1 responsible for the structural derivatization of CPT to synthesize 9-HCPT but also offered potential strategies for enhancing the utilization of silk-based drug delivery systems in tumor therapy.

2023-10-01·Bioorganic Chemistry

Improved anti-tumor activity of fluorinated camptothecin derivatives 9-fluorocamptothecin and 7-ethyl-9-fluorocamptothecin on hepatocellular carcinoma by targeting topoisomerase I

Article

作者: Li, Lei ; Zhang, Zhi-Jun ; Zhu, Li-Zu ; Zhang, Mi ; Yan, Jia-Xuan ; Liu, Ying-Qian ; Xu, Chuan-Rui ; Wang, Zhi-Ping ; Peng, Li-Zeng ; Yang, Cheng-Jie ; Luo, Hong-Bo ; Bai, Yin-Peng

Primary liver cancer is one of the most common malignant cancers of the digestive system that lacks effective chemotherapeutic drugs in clinical settings. Camptothecin (CPT) and its derivatives have been approved for cancer treatment; however, their application is limited by their systemic toxicity. For lead optimization in new drug discovery stages, fluorination is an effective and robust approach to increase the bioavailability and optimize the pharmacokinetics of candidate compounds, thereby improving their efficacy. To obtain new and highly active CPT derivatives, we designed, synthesized, and evaluated two new fluorinated CPT derivatives, 9-fluorocamptothecin (A1) and 7-ethyl-9-fluorocamptothecin (A2), in this study. In vitro, A1 and A2 exhibited more robust anti-tumor activity than topotecan (TPT) in various cancer cells, particularly hepatocellular carcinoma (HCC) cells. In vivo, A1 and A2 exhibited greater anti-tumor activity than TPT in both AKT/Met induced primary HCC mouse models and implanted HepG2 cell xenografts. Acute toxicity tests revealed that A1 and A2 were not lethal and did not cause significant body weight loss at high doses. Moreover, A1 and A2 exhibited no significant toxicity in the mouse liver, heart, lung, spleen, kidney, and hematopoietic systems at therapeutic doses. Mechanistically, A1 and A2 blocked HCC cell proliferation by inhibiting the enzymatic activity of Topo I, subsequently inducing DNA damage, cell cycle arrest, and apoptosis. In summary, our results indicate that fluorination improves the anti-tumor activity of CPT while decreasing its toxicity and highlight the application potential of fluorination products A1 and A2 in clinical settings.

2022-03-01·American Journal of Physiology-Cell Physiology3区 · 生物学

Chloride channels with ClC-1-like properties differentially regulate the excitability of dopamine receptor D1- and D2-expressing striatal medium spiny neurons

3区 · 生物学

Article

作者: Nass, Sara R. ; Yarotskyy, Viktor ; Hahn, Yun K. ; Lark, Arianna R. S. ; Knapp, Pamela E. ; Hauser, Kurt F. ; McQuiston, A. Rory ; Marone, Michael G.

Dynamic chloride (Cl−) regulation is critical for synaptic inhibition. In mature neurons, Cl− influx and extrusion are primarily controlled by ligand-gated anion channels (GABAA and glycine receptors) and the potassium chloride cotransporter K+-Cl− cotransporter 2 (KCC2), respectively. Here, we report for the first time, to our knowledge, a presence of a new source of Cl− influx in striatal neurons with properties similar to chloride voltage-gated channel 1 (ClC-1). Using whole cell patch-clamp recordings, we detected an outwardly rectifying voltage-dependent current that was impermeable to the large anion methanesulfonate (MsO−). The anionic current was sensitive to the ClC-1 inhibitor 9-anthracenecarboxylic acid (9-AC) and the nonspecific blocker phloretin. The mean fractions of anionic current inhibition by MsO−, 9-AC, and phloretin were not significantly different, indicating that anionic current was caused by active ClC-1-like channels. In addition, we found that Cl− current was not sensitive to the transmembrane protein 16A (TMEM16A; Ano1) inhibitor Ani9 and that the outward Cl− rectification was preserved even at a very high intracellular Ca2+ concentration (2 mM), indicating that TMEM16B ( Ano2) did not contribute to the total current. Western blotting and immunohistochemical analyses confirmed the presence of ClC-1 channels in the striatum mainly localized to the somata of striatal neurons. Finally, we found that 9-AC decreased action potential firing frequencies and increased excitability in medium spiny neurons (MSNs) expressing dopamine type 1 (D1) and type 2 (D2) receptors in the brain slices, respectively. We conclude that ClC-1-like channels are preferentially located at the somata of MSNs, are functional, and can modulate neuronal excitability.

100 项与 9-Aminocamptothecin 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	9-Aminocamptothecin	-	DB12515

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
晚期非小细胞肺癌	临床3期	美国	National Cancer Institute	1998-01-01
非霍奇金淋巴瘤	临床3期	美国	National Cancer Institute	1996-04-01
复发性霍奇金淋巴瘤	临床3期	美国	National Cancer Institute	1996-04-01
复发性卵巢癌	临床3期	美国	National Cancer Institute	1995-12-01
皮肤T细胞淋巴瘤	临床3期	美国	National Cancer Institute	1995-05-01
卵巢癌	临床3期	美国	National Cancer Institute	1995-01-01
肿瘤	临床3期	-	Pfizer Inc.	-
肿瘤	临床3期	-	Biogen, Inc.	-
肿瘤	临床3期	-	Arisyn Therapeutics Inc	-
肿瘤	临床3期	-	National Cancer Institute	-

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临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00002745 (CALGB 9551, Pubmed \| Cancer Chemother Pharmacol)	临床2期	淋巴瘤	37	9-aminocamptothecin dimethylacetamide	(廠蓋網獵選範衊獵鹹糧) = 醖衊膚選網齋網糧餘製淵衊鏇願艱鹽餘鑰廠膚 (夢鬱淵顧窪憲構膚淵壓 ) 更多	-	2009-04-01
	临床2期	淋巴瘤	37	9-aminocamptothecin/colloidal dispersion	(廠蓋網獵選範衊獵鹹糧) = 遞鑰蓋鹽繭網壓衊壓獵淵衊鏇願艱鹽餘鑰廠膚 (夢鬱淵顧窪憲構膚淵壓 ) 更多	-	2009-04-01
NCT00002671 (Pubmed \| J Urol)	临床2期	卵巢癌二线	60	9-aminocamptothecin	(範範衊襯鬱鏇獵遞網範) = 簾築選壓醖鏇獵繭蓋蓋遞鑰艱繭積積衊積艱繭 (積鹹鏇壓餘範願範襯餘 ) 更多	积极	2004-01-01