盐酸莎巴比星(Sabarubicin Hydrochloride) - 药物靶点：Top II_在研适应症：难治性肺小细胞癌，小细胞肺癌复发_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Sabarubicin

+ [1]

靶点

Top II

作用机制

Top II抑制剂(拓扑异构酶II抑制剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

非在研机构

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)临床1期

特殊审评特殊审批 (中国)

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结构

分子式C32H37NO13

InChIKeyVQHRZZISQVWPLK-UIRGBLDSSA-N

CAS号211100-13-9

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关联

5

项与盐酸莎巴比星相关的临床试验

CTR20150203 / Recruiting临床1期

注射用盐酸莎巴比星联合顺铂治疗小细胞肺癌（广泛期）安全性、耐受性及药代动力学Ⅰ期临床研究

主要目的：确定注射用盐酸莎巴比星联合顺铂治疗小细胞肺癌（广泛期）患者的最大耐受剂量及剂量限制性毒性，评价注射用盐酸莎巴比星治疗小细胞肺癌患者体内药代动力学特征。次要目的：初步评价注射用盐酸莎巴比星联合顺铂治疗小细胞肺癌（广泛期）的有效性与安全性，为Ⅱ期临床研究推荐合理给药方法。

开始日期2014-08-28

申办/合作机构

北京新沿线医药科技发展有限公司

[+1]

NCT00027781 / Completed临床2期IIT

Open Label Phase II Study of MEN-10755 Administered Every 3 Weeks in Patients With Progressive Hormone Refractory Prostate 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 MEN-10755 in treating patients who have progressive prostate cancer that has not responded to hormone therapy.

开始日期2001-08-01

申办/合作机构

Eortc

NCT00003982 / Completed临床1期IIT

Phase I Study to Determine the Safety of MEN-10755 (BMS-195615) in Patients With a Solid Tumor on a Short I.V. Infusion Given Once Every Week for 3 Consecutive Weeks, Followed by One Week's Rest

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
PURPOSE: Phase I trial to study the effectiveness of MEN-10755 in treating patients who have solid tumors.

开始日期1997-06-01

申办/合作机构

Eortc

100 项与盐酸莎巴比星相关的临床结果

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100 项与盐酸莎巴比星相关的转化医学

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100 项与盐酸莎巴比星相关的专利（医药）

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36

项与盐酸莎巴比星相关的文献（医药）

2016-07-01·Journal of Chromatography B3区 · 医学

Development and validation of a UHPLC–MS/MS method for simultaneous quantitation the plasma concentration of Sabarubicin and its alcohol metabolite M3 in Chinese small cell lung cancer patients

3区 · 医学

Article

作者: Shi, Yuankai ; Zhang, Yan ; Han, Xiaohong ; Wu, Di ; Song, Yuanyuan ; Li, Ning ; Feng, Yun ; Liu, Peng

To support a novel anthracycline agent - Sabarubicin's pharmacokinetics study in Chinese small cell lung cancer patients, a rapid, sensitive, and high throughput ultra-performance liquid chromatography tandem mass spectrometry method using Doxorubicin hydrochloride as internal standard (IS) was developed and validated for simultaneously quantifying Sabarubicin and its alcohol metabolite M3 in human plasma. Plasma samples were pre-extracted with n-hexane to remove hydrophobic interferences and the target compounds were extracted into a 1ml mixture of chloroform and isopropanol (1:1, v/v) and separated on an ACQUITY UPLC BEH Shield RP18 (100mm×2.1mm, 1.7μm) column with gradient mobile phase composed of acetonitrile and water containing 0.1% formic acid. Detection was performed by electrospray ionization in the positive ionization mode under multiple reaction monitoring of the transitions at m/z 644→130 for Sabarubicin, m/z 646→333.2 for M3, and m/z 544→360 for IS. For Sabarubicin and M3, calibration curves over 2-400ng/ml and 0.5-100ng/ml could achieve excellent linearity respectively(r>0.99). Intra- and inter-day precisions were 1.5%-9.1% and 2.2%-12.8%, and accuracy were -9.6% to 0.7% and -4.8% to 5.9% for Sabarubicin and M3 respectively at four concentration levels. The mean recovery for Sabarubicin was 62.4%, 71.9% for M3, and 58.8% for IS. This method was completely validated and successfully applied in the pharmacokinetics study of Sabarubicin and M3 in Chinese small cell lung cancer patients.

2011-08-01·Photochemical & Photobiological Sciences3区 · 化学

Complexes of the antitumoral drugs Doxorubicin and Sabarubicin with telomeric G-quadruplex in basket conformation: ground and excited state properties

3区 · 化学

Article

作者: Stefano Ottani ; Ilse Manet ; Barbara Zambelli ; Giuseppina Andreano ; Luciano Cellai ; Giancarlo Marconi ; Sandra Monti ; Annalisa Masi ; Francesco Manoli

We studied the binding of two anthracycline drugs, Doxorubicin and Sabarubicin, to a model telomeric sequence 5'-d[GGG(TTAGGG)(3)]-3' (21-mer), assuming the basket G-quadruplex (G4) conformation in Na(+)-rich aqueous solution. We used an approach that combines spectroscopic and microcalorimetric techniques to obtain information about ground and excited state properties of the most stable complexes. Both drugs bind to the 21-mer in basket conformation and complexes of 1:1 and 2:1 drug : 21-mer stoichiometry coexist in solution. Binding constants were determined from fluorescence and isothermal titration calorimetry experiments. For both drugs association is driven by enthalpy and disfavoured by entropy in the case of two sequential binding events to different sites. The drug fluorescence is completely quenched in the 1:1 complex, most likely by electron transfer from the guanine system to the anthraquinone moiety, while part of the emission survives in the 2:1 complex. Circular dichroism (CD) of the individual complexes is dominated by the G-quadruplex signal in the UV and by the anthracycline signal in the near-UV and Vis region. The experimental CD spectra combined with conformational calculations at MM level and quantum mechanical calculation of the rotational strength of the electronic transitions afforded information on the binding geometries.

2010-02-01·Bioorganic & Medicinal Chemistry3区 · 医学

Interaction between double helix DNA fragments and the new antitumor agent sabarubicin, Men10755

3区 · 医学

Article

作者: Rosanna Mondelli ; Fabio Animati ; Leonardo Scaglioni ; Stefania Mazzini

Among the disaccharide derivatives of the antitumor anthracycline doxorubicin, sabarubicin (Men10755) is more active and less cytotoxic than doxorubicin. It showed a strong in vivo antitumor activity in all preclinical models examined, in conjunction with a better tolerability, and is now in phase II clinical trials. The interaction of sabarubicin and Men10749 (a similar disaccharide with a different configuration at C-4' of the proximal sugar) with the hexanucleotides d(CGTACG)(2) and d(CGATCG)(2) was studied by a combined use of 2D-(1)H and (31)P NMR techniques. Both (1)H and (31)P chemical shifts of imino protons and phosphates allowed to established the intercalation sites between the CG base pairs, as it occurs for other anthracyclines of the series. The dissociation rate constants (k(off)) of the slow step of the intercalation process were measured for Men10755 and Men10749, by NMR NOE-exchange experiments. The increase of k(off) , with respect of doxorubicin, showed that the intercalation process is significantly faster for both drugs, leading to an average residence time for sabarubicin into d(CGTACG)(2) sixfold shorter than for doxorubicin. This could give account of both higher cytoplasmic/nuclear ratio and lower cellular uptake of sabarubicin in comparison with doxorubicin and accordingly of the lower cytotoxicity of these disaccharide analogues. A relevant number of NOE interactions allowed the structure of the complexes in solution to be derived through restrained MD calculations. NMR-DOSY experiments were performed with several drug/oligonucleotide mixtures in order to determine the structure and the dimension of the aggregates.

100 项与盐酸莎巴比星相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	盐酸莎巴比星	-	DB12410

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
去势抵抗性前列腺癌	药物发现	西班牙	Eortc	2001-08-01
去势抵抗性前列腺癌	药物发现	以色列	Eortc	2001-08-01
去势抵抗性前列腺癌	药物发现	瑞士	Eortc	2001-08-01
去势抵抗性前列腺癌	药物发现	德国	Eortc	2001-08-01
去势抵抗性前列腺癌	药物发现	比利时	Eortc	2001-08-01
去势抵抗性前列腺癌	药物发现	法国	Eortc	2001-08-01
睾丸生殖细胞肿瘤	药物发现	奥地利	Eortc	1997-06-01
实体瘤	药物发现	葡萄牙	Eortc	1997-04-01
实体瘤	药物发现	希腊	Eortc	1997-04-01
实体瘤	药物发现	意大利	Eortc	1997-04-01

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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


ASCO2010	临床1/2期	广泛期小细胞肺癌一线	-	Sabarubicin (SABA) + cisplatin (DDP)	鏇繭遞鏇淵廠衊網鑰夢(衊範憲醖願願艱鹹網鬱) = 鹽鬱網艱淵衊餘壓壓繭壓壓糧衊觸網積餘鬱鹽 (鏇積醖淵選鹽願憲艱繭 ) 更多	-	2010-05-20
ASCO2008	临床2期	广泛期小细胞肺癌	26	Sabarubicin	(構衊廠鹹鑰衊窪獵構積) = 製築廠觸壓餘醖網廠窪製艱淵製簾廠衊醖鏇鏇 (鹹鏇壓鏇憲繭膚襯積夢, 22.43 ~ 57.46) 更多	-	2008-05-20
NCT00027781 (Pubmed \| Eur J Cancer Care (Engl))	临床2期	去势抵抗性前列腺癌	37	Sabarubicin (MEN-10755)	(艱構壓鑰壓夢積製築製) = 廠齋鹽襯膚餘構遞齋壓廠艱窪齋蓋選獵遞鑰鏇 (鹹夢醖齋鬱餘蓋鹹夢窪 ) 更多	-	2006-01-01