Delving into the Latest Updates on Becatecarin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Becatecarin (USAN/INN), Rebeccamycin analogue

+ [10]

Target

DNA x Top I

Action

inhibitors

Mechanism

DNA inhibitors(DNA inhibitors), TOP1 inhibitors(DNA topoisomerase I inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersOther Diseases

Active Indication-

Inactive Indication

Advanced Bile Duct CarcinomaBiliary Tract Neoplasms

Originator Organization

Bristol Myers Squibb Co.

Active Organization-

Inactive Organization

Helsinn Healthcare SA

Bristol Myers Squibb Co.

License Organization

Helsinn Healthcare SA

Exelixis, Inc.

Bristol Myers Squibb Co.

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC33H34Cl2N4O7

InChIKeyJSKFWUPVIZYJMR-UDOAKELVSA-N

CAS Registry119673-08-4

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

Start Date01 May 2004

Sponsor / Collaborator

National Cancer Institute

NCT00086983

/ TerminatedPhase 1IIT

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

Start Date01 May 2004

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with Becatecarin

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100 Translational Medicine associated with Becatecarin

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100 Patents (Medical) associated with Becatecarin

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152

Literatures (Medical) associated with Becatecarin

20 Sep 2024·ACS Synthetic Biology

GOLDBAR: A Framework for Combinatorial Biological Design

Article

Author: Gordon, D. Benjamin ; Gould, Dany ; Akavoor, Vidya ; Roehner, Nicholas ; Densmore, Douglas ; Qin, Lucy ; Voigt, Christopher ; Roberts, James ; Lapets, Andrei

With the rise of new DNA part libraries and technologies for assembling DNA, synthetic biologists are increasingly constructing and screening combinatorial libraries to optimize their biological designs. As combinatorial libraries are used to generate data on design performance, new rules for composing biological designs will emerge. Most formal frameworks for combinatorial design, however, do not yet support formal comparison of design composition, which is needed to facilitate automated analysis and machine learning in massive biological design spaces. To address this need, we introduce a combinatorial design framework called GOLDBAR. Compared with existing frameworks, GOLDBAR enables synthetic biologists to intersect and merge the rules for entire classes of biological designs to extract common design motifs and infer new ones. Here, we demonstrate the application of GOLDBAR to refine/validate design spaces for TetR-homologue transcriptional logic circuits, verify the assembly of a partial nif gene cluster, and infer novel gene clusters for the biosynthesis of rebeccamycin. We also discuss how GOLDBAR could be used to facilitate grammar-based machine learning in synthetic biology.

01 Jul 2023·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

Author: 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.

01 Apr 2023·Journal of Pharmacy and Pharmacology

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

Article

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

100 Deals associated with Becatecarin

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External Link

KEGG	Wiki	ATC	Drug Bank
D03220	-	-	DB06362

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Bile Duct Carcinoma	Phase 3	Belgium	Helsinn Healthcare SA	01 Sep 2004
Advanced Bile Duct Carcinoma	Phase 3	Germany	Helsinn Healthcare SA	01 Sep 2004
Advanced Bile Duct Carcinoma	Phase 3	Hungary	Helsinn Healthcare SA	01 Sep 2004
Advanced Bile Duct Carcinoma	Phase 3	United Kingdom	Helsinn Healthcare SA	01 Sep 2004
Advanced Bile Duct Carcinoma	Phase 3	United States	Helsinn Healthcare SA	01 Sep 2004
Advanced Bile Duct Carcinoma	Phase 3	Spain	Helsinn Healthcare SA	01 Sep 2004
Advanced Bile Duct Carcinoma	Phase 3	France	Helsinn Healthcare SA	01 Sep 2004
Advanced Bile Duct Carcinoma	Phase 3	Canada	Helsinn Healthcare SA	01 Sep 2004
Advanced Bile Duct Carcinoma	Phase 3	Poland	Helsinn Healthcare SA	01 Sep 2004
Biliary Tract Neoplasms	Phase 3	-	Bristol Myers Squibb Co.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00084487 (CTgov)	Phase 2	Recurrent Lung Small Cell Carcinoma \| Extensive stage Small Cell Lung Cancer	21	Rebeccamycin	(ndsbvviosu) = ptdebvdwwf ncuwvtlret (zmoqvbdrti, ewxldkobdg - sdepsvocva) View more	-	01 Jan 2014
ASCO2004	Phase 2	Hormone refractory breast cancer	-	Rebeccamycin analog 500 mg/m2 IV bolus every 21 days	(hmihuztgpl) = blvgaifcmk jgghzuuwjj (junkjojuki ) View more	Negative	15 Jul 2004
ASCO2004	Phase 2	Hormone refractory breast cancer	-	Rebeccamycin analog 140 mg/m2 IV bolus daily x 5 days, every 21 days	(hmihuztgpl) = vqvoajouhp jgghzuuwjj (junkjojuki ) View more	Negative	15 Jul 2004