Delving into the Latest Updates on Sabarubicin Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Sabarubicin

+ [1]

Target

Top II

Mechanism

Top II inhibitors(Topoisomerase II inhibitors)

Therapeutic Areas

NeoplasmsRespiratory Diseases

Active Indication

Refractory Lung Small Cell CarcinomaSmall cell lung cancer recurrent

Inactive Indication

Castration-Resistant Prostatic CancerTesticular Germ Cell Tumor

Originator Organization

NovoTek Therapeutics, Inc.

Active Organization

NovoTek Therapeutics, Inc.

Hefei Cosource Pharmaceutical, Inc.

Inactive Organization

Eortc

Drug Highest PhasePhase 1

First Approval Date-

RegulationSpecial Review Project (CN)

Login to view timeline

Structure

Molecular FormulaC32H37NO13

InChIKeyVQHRZZISQVWPLK-UIRGBLDSSA-N

CAS Registry211100-13-9

View All Structures (2)

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。

[Translation]

Primary objective: To determine the maximum tolerated dose and dose-limiting toxicity of sabalibixin hydrochloride for injection combined with cisplatin in the treatment of patients with small cell lung cancer (extensive stage), and to evaluate the pharmacokinetic characteristics of sabalibixin hydrochloride for injection in the treatment of patients with small cell lung cancer. Secondary objective: To preliminarily evaluate the efficacy and safety of sabalibixin hydrochloride for injection combined with cisplatin in the treatment of small cell lung cancer (extensive stage), and to recommend a reasonable dosing method for phase II clinical studies.

Start Date28 Aug 2014

Sponsor / Collaborator

NovoTek Therapeutics, Inc.

[+1]

NCT00027781 / CompletedPhase 2IIT

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.

Start Date01 Aug 2001

Sponsor / Collaborator

Eortc

NCT00003982 / CompletedPhase 1IIT

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.

Start Date01 Jun 1997

Sponsor / Collaborator

Eortc

100 Clinical Results associated with Sabarubicin Hydrochloride

Login to view more data

100 Translational Medicine associated with Sabarubicin Hydrochloride

Login to view more data

100 Patents (Medical) associated with Sabarubicin Hydrochloride

Login to view more data

36

Literatures (Medical) associated with Sabarubicin Hydrochloride

01 Jul 2016·Journal of Chromatography BQ3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: 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.

01 Aug 2011·Photochemical & Photobiological SciencesQ3 · CHEMISTRY

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

Q3 · CHEMISTRY

Article

Author: 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.

01 Feb 2010·Bioorganic & Medicinal ChemistryQ3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: 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 Deals associated with Sabarubicin Hydrochloride

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
-	Sabarubicin Hydrochloride	-	DB12410

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Castration-Resistant Prostatic Cancer	Discovery	ES	Eortc	01 Aug 2001
Castration-Resistant Prostatic Cancer	Discovery	IL	Eortc	01 Aug 2001
Castration-Resistant Prostatic Cancer	Discovery	CH	Eortc	01 Aug 2001
Castration-Resistant Prostatic Cancer	Discovery	DE	Eortc	01 Aug 2001
Castration-Resistant Prostatic Cancer	Discovery	BE	Eortc	01 Aug 2001
Castration-Resistant Prostatic Cancer	Discovery	FR	Eortc	01 Aug 2001
Testicular Germ Cell Tumor	Discovery	AT	Eortc	01 Jun 1997
Solid tumor	Discovery	PT	Eortc	01 Apr 1997
Solid tumor	Discovery	GR	Eortc	01 Apr 1997
Solid tumor	Discovery	IT	Eortc	01 Apr 1997

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2010	Phase 1/2	Extensive stage Small Cell Lung Cancer First line	-	Sabarubicin (SABA) + cisplatin (DDP)	pyyyvcxtar(xqpeyxulgi) = lposdcltjn ngfownuqhe (inywtpoetc ) View more	-	20 May 2010
ASCO2008	Phase 2	Extensive stage Small Cell Lung Cancer	26	Sabarubicin	(blkogmfevy) = agfxiyfdjj bheuxshidc (zxoerzfovg, 22.43 - 57.46) View more	-	20 May 2008
NCT00027781 (Pubmed \| Eur J Cancer Care (Engl))	Phase 2	Castration-Resistant Prostatic Cancer	37	Sabarubicin (MEN-10755)	(knxshjyxnr) = mwrbawsnhs medpipukjz (sovogaghqs ) View more	-	01 Jan 2006