贝特卡令(Becatecarin) - 药物靶点：DNA x TOP1_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Becatecarin (USAN/INN)、Rebeccamycin analogue

+ [9]

靶点

DNA x TOP1

作用机制

DNA抑制剂(DNA抑制剂)、TOP1抑制剂(DNA拓扑异构酶I抑制剂)

治疗领域

肿瘤消化系统疾病

在研适应症-

非在研适应症

晚期胆管癌胆道肿瘤

原研机构

Bristol Myers Squibb Co.

在研机构-

非在研机构

Helsinn Healthcare SA

Bristol Myers Squibb Co.

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C33H34Cl2N4O7

InChIKeyJSKFWUPVIZYJMR-UDOAKELVSA-N

CAS号119673-08-4

关联

13

项与贝特卡令相关的临床试验

NCT00090025 / Terminated临床3期

A Phase 3 Multicenter, Open Label, Randomized Study of XL119 Versus 5-Fluorouracil (5-FU) Plus Leucovorin (LV) in Subjects With Advanced Biliary Tumors Not Amenable to Conventional Surgery

The main purpose of this study is to determine if XL119 is more effective than the combination of 5-fluorouracil (5FU) and leucovorin (LV) in prolonging the survival of subjects with advanced biliary tumors.

开始日期2004-09-01

申办/合作机构

Helsinn Healthcare SA

NCT00086983 / Terminated临床1期IIT

A Phase I Study of XL119 (Rebeccamycin Analogue) in Combination With Oxaliplatin in Patients With Refractory Solid Tumors

This phase I trial is studying the side effects and best dose of rebeccamycin analog and oxaliplatin in treating patients with refractory solid tumors. Drugs used in chemotherapy, such as rebeccamycin analog and oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells

开始日期2004-05-01

申办/合作机构

National Cancer Institute

NCT00087204 / Completed临床1期IIT

A Phase I Study Of XL119 In Patients With Relapsed Or Refractory Acute Myeloid Leukemia, Myelodysplastic Syndromes, Acute Lymphocytic Leukemia, Or Chronic Myeloid Leukemia In Blastic-Phase

This phase I trial is studying the side effects and best dose of rebeccamycin analog in treating patients with relapsed or refractory acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia, or chronic myelogenous leukemia in blast phase. Drugs used in chemotherapy, such as rebeccamycin analog, work in different ways to stop cancer cells from dividing so they stop growing or die

开始日期2004-05-01

申办/合作机构

National Cancer Institute

100 项与贝特卡令相关的临床结果

登录后查看更多信息

100 项与贝特卡令相关的转化医学

登录后查看更多信息

100 项与贝特卡令相关的专利（医药）

登录后查看更多信息

141

项与贝特卡令相关的文献（医药）

2023-07-01·Journal of Fluorescence

Molecular Dynamics and Multi-Spectroscopic of the Interaction Behavior between Bladder Cancer Cells and Calf Thymus DNA with Rebeccamycin: Apoptosis through the Down Regulation of PI3K/AKT Signaling Pathway

Article

作者: Chamani, Jamshidkhan ; Malek-Esfandiari, Zohreh ; Mokaberi, Parisa ; Amiri-Tehranizadeh, Zeinab ; Rezvani-Noghani, Azadeh ; Sohrabi, Tahmineh

The interaction of Rebeccamycin with calf thymus (ctDNA) in the absence and presence of H1 was investigated by molecular dynamics, multi-spectroscopic, and cellular techniques. According to fluorescence and circular dichroism spectroscopies, Rebeccamycin interacted with ctDNA in the absence of H1 through intercalator or binding modes, while the presence of H1 resulted in revealing theintercalator, as the dominant role, and groove binding modes of ctDNA-Rebeccamycin complex. The binding constants, which were calculated to be 1.22 × 10⁴ M^-1 and 7.92 × 10⁵ M^-1 in the absence and presence of H1, respectively, denoted the strong binding of Rebeccamycin with ctDNA. The binding constants of Rebeccamycin with ct DNA in the absence and presence of H1 were calculated at 298, 303 and 308 K. Considering the thermodynamic parameters (ΔH⁰ and ΔS⁰), both vander waals forces and hydrogen bonds played predominant roles throughout the binding of Rebeccamycin to ctDNA in the absence and presence of H1. The outcomes of circular dichroism suggested the lack of any major conformational changes in ctDNA upon interacting with Rebeccamycin, except some perturbations in native B-DNA at local level. Additionally, the effect of NaCl and KI on ctDNA-Rebeccamycin complex provided further evidence for the reliance of their interaction modes on substituted groups. The observed increase in the relative viscosity of ctDNA caused by the enhancement of Rebeccamycin confirmed their intercalation and groove binding modes in the absence and presence of H1. Moreover, the assessments of molecular docking simulation corroborated these experimental results and also elucidated the effectiveness of Rebeccamycinin inhibiting and proliferating T24 and 5637 cells. Meanwhile, the ability of Rebeccamycin in inhibiting cell proliferation and tumor growth through the induction of apoptosis by down regulating the PI3K/AKT signaling pathway were provided.

2023-04-07·Journal of Pharmacy and Pharmacology

Indolocarbazole alkaloid Loonamycin A inhibits triple-negative breast cancer cell stemness and Notch signalling

Article

作者: Wang, Yixue ; Shen, Yan ; Chen, Zhixiu ; Zhang, Bo ; Xu, Qiang ; Li, Wuhao ; Xue, Wenwen ; Zhou, Lin ; Ge, Huiming ; Wang, Liwei ; Yu, Ying

AbstractObjectivesEnrichment for therapy-resistant cancer stem cells hampers the treatment of triple-negative breast cancer. Targeting these cells via suppression of Notch signalling can be a potential therapeutic strategy. This study aimed to uncover the mode of action of a new indolocarbazole alkaloid loonamycin A against this incurable disease.MethodsThe anticancer effects were examined in triple-negative breast cancer cells using in vitro methods, including cell viability and proliferation assays, wound-healing assay, flow cytometry and mammosphere formation assay. RNA-seq technology was used to analyse the gene expression profiles in loonamycin A-treated cells. Real-time RT-PCR and western blot were to evaluate the inhibition of Notch signalling.Key findingsLoonamycin A has stronger cytotoxicity than its structural analog rebeccamycin. Besides inhibiting cell proliferation and migration, loonamycin A reduced CD44high/CD24low/− sub-population, mammosphere formation, as well as the expression of stemness-associated genes. Co-administration of loonamycin A enhanced antitumour effects of paclitaxel by inducing apoptosis. RNA sequencing results showed that loonamycin A treatment caused the inhibition of Notch signalling, accompanied by the decreased expression of Notch1 and its targeted genes.ConclusionsThese results reveal a novel bioactivity of indolocarbazole-type alkaloids and provide a promising Notch-inhibiting small molecular candidate for triple-negative breast cancer therapy.

2023-01-01·Frontiers in bioengineering and biotechnology

Morphology engineering for novel antibiotics: Effect of glass microparticles and soy lecithin on rebeccamycin production and cellular morphology of filamentous actinomycete Lentzea aerocolonigenes.

Article

作者: Klose, Leon ; Schrinner, Kathrin ; Schrader, Marcel ; Kwade, Arno ; Krull, Rainer ; Kozanecka, Zuzanna Justyna ; Weiß, Hannah ; Dinius, Anna ; Brauns, Henry

Lentzea aerocolonigenes, as an actinomycete, is a natural producer of the antibiotic and antitumoral drug rebeccamycin. Due to the filamentous cellular morphology handling in cultivations is challenging; therefore, morphology engineering techniques are mandatory to enhance productivity. One promising approach described in the literature is the addition of mineral particles in the micrometer range to precisely adjust cellular morphology and the corresponding product synthesis (microparticle-enhanced cultivation, MPEC). Glass microparticles are introduced in this study as a novel supplementation type for bioprocess intensification in filamentous organisms. Several investigations were conducted to screen for an optimal particle setup, including particle size and concentration regarding their impact and effects on enhanced productivity, microparticle incorporation behavior into the biopellets, the viability of pellets, and morphological changes. Glass microparticles (10 g·L^-1) with a median diameter of 7.9 µm, for instance, induced an up to fourfold increase in product synthesis accompanied by overall enhanced viability of biomass. Furthermore, structural elucidations showed that biopellets isolated from MPEC tend to have lower hyphal density than unsupplemented control pellets. In this context, oxygen microprofiling was conducted to better understand how internal structural changes interwind with oxygen supply into the pellets. Here, the resulting oxygen profiles are of a contradictive trend of steeper oxygen consumption with increasing glass microparticle supplementation. Eventually, MPEC was combined with another promising cultivation strategy, the supplementation of soy lecithin (7.5 g·L^-1), to further increase the cultivation performance. A combination of both techniques in an optimized setup resulted in a rebeccamycin concentration of 213 mg·L^-1 after 10 days of cultivation, the highest value published so far for microparticle-supplemented shake flask cultivations of L. aerocolonigenes.

100 项与贝特卡令相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D03220	-	-	DB06362

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
晚期胆管癌	临床3期	加拿大	Helsinn Healthcare SA	2004-09-01
晚期胆管癌	临床3期	匈牙利	Helsinn Healthcare SA	2004-09-01
晚期胆管癌	临床3期	英国	Helsinn Healthcare SA	2004-09-01
晚期胆管癌	临床3期	法国	Helsinn Healthcare SA	2004-09-01
晚期胆管癌	临床3期	德国	Helsinn Healthcare SA	2004-09-01
晚期胆管癌	临床3期	比利时	Helsinn Healthcare SA	2004-09-01
晚期胆管癌	临床3期	意大利	Helsinn Healthcare SA	2004-09-01
胆道肿瘤	临床3期	-	Bristol Myers Squibb Co.	-
晚期胆管癌	临床2期	西班牙	Helsinn Healthcare SA	2004-09-01
晚期胆管癌	临床2期	波兰	Helsinn Healthcare SA	2004-09-01

登录后查看更多信息

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


NCT00084487 (CTgov)	临床2期	小细胞肺癌复发 \| 广泛期小细胞肺癌	21	Rebeccamycin	鹽鑰衊廠鏇製範鏇範夢(築鹹齋窪夢鬱艱衊壓壓) = 夢壓憲顧衊憲鏇襯簾願構選襯廠願鏇齋選製鹽 (鹹鑰遞選艱廠繭壓膚顧, 窪網繭壓簾淵壓夢鏇選 ~ 淵築鬱網遞蓋鏇簾簾憲) 更多	-	2014-01-01
NCT00005997 (Pubmed \| Cancer Chemother Pharmacol)	临床2期	胆道肿瘤	72	Rebeccamycin analogue (RA)	(醖築鹽遞齋醖遞鑰鹹鏇) = 鹹衊醖膚鹹願艱膚壓選繭鏇蓋夢構窪窪齋繭願 (網衊齋鹽遞構遞壓鏇艱 ) 更多	-	2009-12-01
NCT00006102 (Pubmed \| Pediatr Blood Cancer)	临床2期	实体瘤	200	Rebeccamycin analogue NSC #655649	(夢醖膚淵齋觸鏇願製壓) = 鹹鑰壓膚構壓廠鬱艱鬱廠簾築鑰鏇膚網艱鹽願 (築觸構選鹹網顧鏇獵餘 ) 更多	不佳	2008-03-01
ASCO2004	临床2期	激素难治性乳腺癌	-	Rebeccamycin analog 500 mg/m2 IV bolus every 21 days	(鹹膚鬱糧願膚簾積壓窪) = 範鹹鏇淵鏇淵選顧窪醖網糧壓簾網獵淵鹽鏇憲 (憲鹹獵蓋積製壓窪鑰廠 ) 更多	不佳	2004-07-15
ASCO2004	临床2期	激素难治性乳腺癌	-	Rebeccamycin analog 140 mg/m2 IV bolus daily x 5 days, every 21 days	(鹹膚鬱糧願膚簾積壓窪) = 觸範鏇網夢遞鑰膚廠鬱網糧壓簾網獵淵鹽鏇憲 (憲鹹獵蓋積製壓窪鑰廠 ) 更多	不佳	2004-07-15