PIXANTRONE DIMALEATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H19N5O2.2C4H4O4
Molecular Weight	557.5094
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	2
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.NCCNC1=CC=C(NCCN)C2=C1C(=O)C3=C(C=NC=C3)C2=O

InChI

InChIKey=SVAGFBGXEWPNJC-SPIKMXEPSA-N

InChI=1S/C17H19N5O2.2C4H4O4/c18-4-7-21-12-1-2-13(22-8-5-19)15-14(12)16(23)10-3-6-20-9-11(10)17(15)24;2*5-3(6)1-2-4(7)8/h1-3,6,9,21-22H,4-5,7-8,18-19H2;2*1-2H,(H,5,6)(H,7,8)/b;2*2-1-

HIDE SMILES / InChI

Description
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002055/WC500127970.pdf
Curator's Comment: description was created based on several sources, including: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002055/WC500127968.pdf | https://www.medicines.org.uk/emc/PIL.30473.latest.pdf

Pixantrone is a novel anthracenedione. It is a weak inhibitor of topoisomerase II. Pixantrone directly alkylates DNA forming stable DNA adducts and cross-strand breaks. Pixuvri is approved for the treatment of adult patients with multiply relapsed or refractory aggressive Non-Hodgkin lymphomas. It is used for patients whose cancer does not respond or has returned after they have received other chemotherapy treatments. The most frequent AE were seen in the blood (mainly neutropaenia), gastrointestinal (nausea, abdominal pain, constipation) and respiratory systems (cough, dyspnea). No drug-drug interaction studies have been submitted and no drug interactions have been reported in human subjects

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA topoisomerase II alpha 37 Target ID: CHEMBL1806 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002055/WC500127968.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/26660439	Inhibitor 8297
DNA topoisomerase II beta 14 Target ID: CHEMBL3396 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002055/WC500127968.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/26660439	Inhibitor 8297
DNA 278 Target ID: CHEMBL2311221 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002055/WC500127968.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/26660439	Modulator 828

Conditions

Condition	Modality	Highest Phase	Product
Non-Hodgkin's lymphoma 79 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002055/WC500127968.pdf	Primary	Approved 8429	Pixuvri Approved Use Pixuvri is used for the treatment of adult patients with multiply relapsed or refractory aggressive Non-Hodgkin lymphomas. Launch Date 2012
Diffuse large B-cell lymphoma 20 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27093976	Primary	Phase III 656	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11205916	Primary	Phase II 1132	Unknown Approved Use Unknown
Acute myelogenous leukemia 19 Sources: https://clinicaltrials.gov/ct2/show/NCT00106600	Primary	Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Topoisomerase II DNA cleavage stimulation, DNA binding activity, cytotoxicity, and physico-chemical properties of 2-aza- and 2-aza-oxide-anthracenedione derivatives.	1995 Jul	7623772
A phase I and pharmacokinetic study of the novel aza-anthracenedione compound BBR 2778 in patients with advanced solid malignancies.	2001 Jan	11205916
Phase I study of BBR 2778, a new aza-anthracenedione, in advanced or refractory non-Hodgkin's lymphoma.	2001 May	11432625
Bbr 2778, an aza-anthracenedione endowed with preclinical anticancer activity and lack of delayed cardiotoxicity.	2001 Nov-Dec	11989596
Characterization of anthracenediones and their photoaffinity analogs.	2002 Mar 15	11931847
Solid-state characterization of a novel chemotherapeutic drug.	2003 Mar	12587119
Pixantrone (Novuspharma).	2003 May	12789604
A comparison of the benefits of mitoxantrone and other recent therapeutic approaches in multiple sclerosis.	2004 Apr	15102561
New immunosuppressants with potential implication in multiple sclerosis.	2004 Aug 15	15261567
Pixantrone (BBR2778): a new immunosuppressant in multiple sclerosis with a low cardiotoxicity.	2004 Aug 15	15261566
Pixantrone (BBR2778) reduces the severity of experimental allergic encephalomyelitis.	2004 Jun	15145604
The role of pixantrone in the treatment of non-Hodgkin's lymphoma.	2005 Aug	16050797
Effects of pixantrone on immune-cell function in the course of acute rat experimental allergic encephalomyelitis.	2005 Nov	16120465
Diagnosis and management of lymphoma.	2006 Jul	16879767
EXTEND PIX301: a phase III randomized trial of pixantrone versus other chemotherapeutic agents as third-line monotherapy in patients with relapsed, aggressive non-Hodgkin's lymphoma.	2006 Sep	17026830
Pixantrone can be activated by formaldehyde to generate a potent DNA adduct forming agent.	2007	17483512
A phase I/II trial of pixantrone (BBR2778), methylprednisolone, cisplatin, and cytosine arabinoside (PSHAP) in relapsed/refractory aggressive non-Hodgkin's lymphoma.	2007 Feb	17325899
Compared benefit of approved and experimental immunosuppressive therapeutic approaches in multiple sclerosis.	2007 Jun	17516874
Pixantrone (BBR 2778) has reduced cardiotoxic potential in mice pretreated with doxorubicin: comparative studies against doxorubicin and mitoxantrone.	2007 Jun	17285358
Pixantrone: a novel aza-anthracenedione in the treatment of non-Hodgkin's lymphomas.	2007 Oct	17922631
Considerations with newer regimens for indolent non-Hodgkin lymphoma.	2008 Aug	18952543
Pixantrone (BBR2778) reduces the severity of experimental autoimmune myasthenia gravis in Lewis rats.	2008 Feb 15	18250482
Synthesis and antitumor evaluation of bis aza-anthracene-9,10-diones and bis aza-anthrapyrazole-6-ones.	2008 Feb 28	18232651
Formaldehyde-activated Pixantrone is a monofunctional DNA alkylator that binds selectively to CpG and CpA doublets.	2008 Jul	18413664
CE can identify small molecules that selectively target soluble oligomers of amyloid beta protein and display antifibrillogenic activity.	2009 Apr	19306269
Pixantrone: a promising drug in the treatment of non-Hodgkin lymphomas.	2009 May	19450173
Pixantrone maleate for non-Hodgkin's lymphoma.	2009 Nov	20126672
Pixantrone for the treatment of aggressive non-Hodgkin lymphoma.	2010 Aug	20569087
DNA binding by pixantrone.	2010 Dec 7	20865205
Lymphoma researchers in search of molecular targets.	2010 Jul 21	20616351
Can anthracycline therapy for pediatric malignancies be less cardiotoxic?	2010 Nov	20820959
New anthracenedione derivatives with improved biological activity by virtue of stable drug-DNA adduct formation.	2010 Oct 14	20860366
Differential targeting of immune-cells by Pixantrone in experimental myasthenia gravis.	2013 May 15	23523328

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose is 50 mg/m^2 of pixantrone on day 1, 8 and 15 of each 28-day cycle for up to 6 cycles.

Route of Administration: Intravenous

In Vitro Use Guide

In separate 72-hour growth-inhibitory assays using direct cell counting, the etoposide-resistant K/VP.5 cells were 21.6-fold cross-resistant to pixantrone, yielding IC50 values of 0.04 and 0.85 uM for K562 and K/VP.5 cells, respectively.

Name

Type

Language

PIXANTRONE DIMALEATE

Official Name

English

PIXANTRONE DIMALEATE SALT

Common Name

English

BBR 2778 DIMALEATE

Code

English

Pixantrone maleate [WHO-DD]

Common Name

English

PIXANTRONE DIMALEATE SALT [MI]

Common Name

English

PIXUVRI

Brand Name

English

PIXANTRONE DIMALEATE [USAN]

Common Name

English

6,9-Bis[(2-aminoethyl)amino]benzo[g]isoquinoline-5,10-dione (2Z)-but-2-enedioate (1:2)

Systematic Name

English

BENZ(G)ISOQUINOLINE-5,10-DIONE, 6,9-BIS((2-AMINOETHYL)AMINO)-, (2Z)-2-BUTENEDIOATE (1:2)

Systematic Name

English

BBR-2778 DIMALEATE

Code

English

PIXANTRONE MALEATE

Common Name

English

NSC-752341

Code

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/09/722