Namitecan(Namitecan) - 药物靶点：Top I_专利_临床

概要

基本信息

药物类型

小分子化药

别名

CPT-188、ST 1968、ST-1968

靶点

Top I

作用方式

抑制剂

作用机制

TOP1抑制剂(DNA拓扑异构酶I抑制剂)

治疗领域

肿瘤

在研适应症-

非在研适应症

实体瘤

原研机构

Sigma-Tau BV

在研机构-

非在研机构

Alfasigma SpA

权益机构-

最高研发阶段无进展临床1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C23H22N4O5

InChIKeyIBTISPLPBBHVSU-UVOOVGFISA-N

CAS号372105-27-6

关联

1

项与 Namitecan 相关的临床试验

NCT01748019

/ Completed临床1期

Phase I Dose Finding and Pharmacokinetic Study of the Intravenous Camptothecin ST1968 in Patients With Solid Tumors

ST1968 is a novel camptothecin derivative which interacts with topoisomerase I-DNA complex, inducing S-Phase specific cytotoxicity. It is endowed with a potent antitumor activity and an increased Therapeutic Index with respect to the clinically used analogues (i.e.irinotecan and topotecan) in some xenograft models (ovary, colon, head & neck, cervix). Anti-tumor activity has been also noted in platinum resistant ovarian cell xenografts and in topoisomerase I mutant prostate cell lines. The acceptable toxicity profile in animals and the activity in camptothecin-resistant cell lines make ST1968 a good candidate for clinical trials.

开始日期2007-06-01

申办/合作机构

Alfasigma SpA

100 项与 Namitecan 相关的临床结果

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100 项与 Namitecan 相关的转化医学

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100 项与 Namitecan 相关的专利（医药）

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18

项与 Namitecan 相关的文献（医药）

2020-11-20·Current topics in medicinal chemistry4区 · 医学

An Overview of Privileged Scaffold: Quinolines and Isoquinolines in Medicinal Chemistry as Anticancer Agents

4区 · 医学

Article

作者: Sangani, Chetan ; Mao, Yanna ; Yao, Yongfang ; Soni, Kunjal

Cancer is one of the most difficult diseases and causes of death for many decades. Many pieces of research are continuously going on to get a solution for cancer. Quinoline and isoquinoline derivatives have shown their possibilities to work as an antitumor agent in anticancer treatment. The members of this privileged scaffold quinoline and isoquinoline have shown their controlling impacts on cancer treatment through various modes. In particular, this review suggests the current scenario of quinoline and isoquinoline derivatives as antitumor agents and refine the path of these derivatives to find and develop new drugs against an evil known as cancer.

2015-07-01·British journal of clinical pharmacology2区 · 医学

Integrative population pharmacokinetic and pharmacodynamic dose finding approach of the new camptothecin compound namitecan (ST1968)

2区 · 医学

Article

作者: D. Hess ; S. Pace ; A. Fasolo ; S. Cresta ; A. Delmonte ; E. Gallerani ; M. Joerger ; C. Sessa ; P. Barbieri ; L. Gianni

Aims:

Namitecan is a new camptothecan compound undergoing early clinical development. This study was initiated to build an integrated pharmacokinetic (PK) and pharmacodynamic (PD) population model of namitecan to guide future clinical development.

Methods:

Plasma concentration–time data, neutrophils and thrombocytes were pooled from two phase 1 studies in 90 patients with advanced solid tumours, receiving namitecan as a 2 h infusion on days 1 and 8 every 3 weeks (D1,8) (n= 34), once every 3 weeks (D1) (n= 29) and on 3 consecutive days (D1–3) (n= 27). A linear three compartment PK model was coupled to a semiphysiological PD‐model for neutrophils and thrombocytes. Data simulations were used to interrogate various dosing regimens and give dosing recommendations.

Results:

Clearance was estimated to be 0.15 l h–1, with a long terminal half‐life of 48 h. Body surface area was not associated with clearance, supporting flat‐dosing of namitecan. A significant and clinically relevant association was found between namitecan area under the concentration–time curve (AUC) and the percentage drop of neutrophils (r2= 0.51,P< 10−4) or thrombocytes (r2= 0.49,P< 10−4). With a target for haematological dose‐limiting toxicity of <20%, the recommended dose was defined as 12.5 mg for the D1,8 regimen, 23 mg for the once every 3 week regimen and 7 mg for the D1–3 regimen.

Conclusion:

This is the first integrated population PK–PD analysis of the new hydrophilic topoisomerase I inhibitor namitecan, that is currently undergoing early clinical development. A distinct relationship was found between drug exposure and haematological toxicity, supporting flat‐dosing once every 3 weeks as the most adequate dosing regimen.

2015-04-01·Investigational new drugs3区 · 医学

Phase-I dose finding and pharmacokinetic study of the novel hydrophilic camptothecin ST-1968 (namitecan) in patients with solid tumors

3区 · 医学

Article

作者: Gallerani, E. ; Barbieri, P. ; Joerger, M. ; Pace, S. ; Delmonte, A. ; Hess, D. ; Sessa, C.

PURPOSE:

This is a first-in-human, phase I, dose-escalation study to determine the maximum tolerated dose (MTD) of intravenous, flat-dosed ST-1968 (namitecan), a new hydrophilic camptothecan derivative.

METHODS:

Namitecan was administered intravenously over 2 h on day 1 and day 8 every 21 days (D1-D8-Q21D), starting at a flat dose of 2.5 mg, and increased according to a 3 + 3 cohort design. Due to frequent skipping of day 8 dosing for cytopenias, the study was expanded to test namitecan dosing on day 1 every 21 days (D1-Q21) at a starting dose of 17.5 mg. Major dose-limiting toxicity (DLT) was defined as grade (G) 4 neutropenia persisting >5 days, febrile neutropenia, G3 thrombocytopenia or G2 non-hematological toxicity.

RESULTS:

Thirty-four patients were included into the D1-D8-Q21D group (2.5, 5, 10, 15, 17.5, 20 mg dosing cohorts), 29 patients into the D1-21D group (17.5, 20, 23, 27, 30 mg dosing cohorts). Neutropenia was the DLT in both groups, with 15 mg being defined as the recommended dose (RD) for the D1-D8-Q21D group, and 23 mg for the D1-Q21D group. Non-hematological toxicity was negligible. One patient with endometrial cancer in the D1-D8-Q21D group and one patient with cholangiocellular carcinoma in the D1-Q21D group experienced a partial remission. Namitecan exhibited fully dose-proportional pharmacokinetics.

CONCLUSIONS:

This study demonstrates clinical safety, favourable pharmacokinetics and preliminary antitumor activity of the novel hydrophilic camptothecin analogue namitecan in patients with heavily pretreated solid malignancies, when given either on a 2 out of 3 weeks or 3-weekly regimen.

100 项与 Namitecan 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12124

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
实体瘤	临床1期	-	Alfasigma SpA	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


ASCO2011	临床1期	-	16	Namitecan	製壓衊醖膚簾鏇顧窪繭(遞遞獵觸築遞積窪醖鑰) = lasting 10+ months 鹹艱窪糧餘網憲壓遞遞 (憲選遞鹹淵壓憲鏇觸鑰 ) 更多	-	2011-05-20
ASCO2009	临床1期	-	31	Namitecan	淵鹽糧鬱齋鹹蓋淵觸鏇(廠獵廠廠糧獵鏇選築簾) = 鹹顧願糧醖顧鏇選蓋餘顧遞範蓋鑰鬱襯鏇憲選 (醖艱淵鹹遞選鹽獵鏇遞 ) 更多	-	2009-05-20