PIXANTRONE DIMALEATE

Possibly Marketed Outside US

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

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Molecular Formula	C17H19N5O2
Molecular Weight	325.3651
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 8504
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 8504
DNA 282 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 846

Conditions

Condition	Modality	Highest Phase	Product
Non-Hodgkin's lymphoma 81 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002055/WC500127968.pdf	Primary	Approved 8583	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 22 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27093976	Primary	Phase III 665	Unknown Approved Use Unknown
Breast cancer 432 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11205916	Primary	Phase II 1147	Unknown Approved Use Unknown
Acute myelogenous leukemia 18 Sources: https://clinicaltrials.gov/ct2/show/NCT00106600	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
52.4 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	5 mg/m² single, intravenous dose: 5 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
213.2 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	10 mg/m² single, intravenous dose: 10 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
483.2 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	16.5 mg/m² single, intravenous dose: 16.5 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
762.4 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	25 mg/m² single, intravenous dose: 25 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1189.6 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	35 mg/m² single, intravenous dose: 35 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1447.5 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	56 mg/m² single, intravenous dose: 56 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2241.9 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	84 mg/m² single, intravenous dose: 84 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
318.1 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11205916/	16.5 mg/m² 1 times / week multiple, intravenous dose: 16.5 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
701.4 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11205916/	25 mg/m² 1 times / week multiple, intravenous dose: 25 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
1193 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11205916/	37.5 mg/m² 1 times / week multiple, intravenous dose: 37.5 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
4297.6 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11205916/	75 mg/m² 1 times / week multiple, intravenous dose: 75 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
7120.8 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11205916/	112.5 mg/m² 1 times / week multiple, intravenous dose: 112.5 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
3852.1 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11205916/	150 mg/m² 1 times / week multiple, intravenous dose: 150 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
438.1 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	5 mg/m² single, intravenous dose: 5 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
451.1 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	10 mg/m² single, intravenous dose: 10 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
781.9 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	16.5 mg/m² single, intravenous dose: 16.5 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1321.2 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	25 mg/m² single, intravenous dose: 25 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2530.5 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	35 mg/m² single, intravenous dose: 35 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2266.8 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	56 mg/m² single, intravenous dose: 56 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3679.9 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	84 mg/m² single, intravenous dose: 84 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
502.6 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11205916/	16.5 mg/m² 1 times / week multiple, intravenous dose: 16.5 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
1074.8 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11205916/	25 mg/m² 1 times / week multiple, intravenous dose: 25 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
1773.4 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11205916/	37.5 mg/m² 1 times / week multiple, intravenous dose: 37.5 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
5027.1 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11205916/	75 mg/m² 1 times / week multiple, intravenous dose: 75 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
7882.3 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11205916/	112.5 mg/m² 1 times / week multiple, intravenous dose: 112.5 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
8058.5 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11205916/	150 mg/m² 1 times / week multiple, intravenous dose: 150 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
982 ng × h/mL DRUG LABEL https://ec.europa.eu/health/documents/community-register/2017/20170322137183/anx_137183_en.pdf	33 mg/m² 1 times / week multiple, intravenous dose: 33 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
1727 ng × h/mL DRUG LABEL https://ec.europa.eu/health/documents/community-register/2017/20170322137183/anx_137183_en.pdf	49 mg/m² 1 times / week multiple, intravenous dose: 49 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
3811 ng × h/mL DRUG LABEL https://ec.europa.eu/health/documents/community-register/2017/20170322137183/anx_137183_en.pdf	88 mg/m² 1 times / week multiple, intravenous dose: 88 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
36.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	5 mg/m² single, intravenous dose: 5 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
21.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	10 mg/m² single, intravenous dose: 10 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
20.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	16.5 mg/m² single, intravenous dose: 16.5 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
19.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	25 mg/m² single, intravenous dose: 25 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
31.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	35 mg/m² single, intravenous dose: 35 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
22.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	56 mg/m² single, intravenous dose: 56 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
17.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11432625/	84 mg/m² single, intravenous dose: 84 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
11.23 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11205916/	16.5 mg/m² 1 times / week multiple, intravenous dose: 16.5 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
16.46 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11205916/	25 mg/m² 1 times / week multiple, intravenous dose: 25 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
13.77 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11205916/	37.5 mg/m² 1 times / week multiple, intravenous dose: 37.5 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
8.89 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11205916/	75 mg/m² 1 times / week multiple, intravenous dose: 75 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
9.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11205916/	112.5 mg/m² 1 times / week multiple, intravenous dose: 112.5 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
11.91 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11205916/	150 mg/m² 1 times / week multiple, intravenous dose: 150 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
23.3 h DRUG LABEL https://ec.europa.eu/health/documents/community-register/2017/20170322137183/anx_137183_en.pdf	33 mg/m² 1 times / week multiple, intravenous dose: 33 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
23.3 h DRUG LABEL https://ec.europa.eu/health/documents/community-register/2017/20170322137183/anx_137183_en.pdf	49 mg/m² 1 times / week multiple, intravenous dose: 49 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
23.3 h DRUG LABEL https://ec.europa.eu/health/documents/community-register/2017/20170322137183/anx_137183_en.pdf	88 mg/m² 1 times / week multiple, intravenous dose: 88 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Analyte	Population
50% DRUG LABEL https://ec.europa.eu/health/documents/community-register/2017/20170322137183/anx_137183_en.pdf	33 mg/m² 1 times / week multiple, intravenous dose: 33 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
50% DRUG LABEL https://ec.europa.eu/health/documents/community-register/2017/20170322137183/anx_137183_en.pdf	49 mg/m² 1 times / week multiple, intravenous dose: 49 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
50% DRUG LABEL https://ec.europa.eu/health/documents/community-register/2017/20170322137183/anx_137183_en.pdf	88 mg/m² 1 times / week multiple, intravenous dose: 88 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PIXANTRONE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
240 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose Dose: 240 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 240 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/11094309/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/11094309/	DLT: Neutropenia... Other AEs: Thrombocytopenia... Dose limiting toxicities: Neutropenia (grade 4, 40%) Other AEs: Thrombocytopenia (grade 4, 20%) Sources: https://pubmed.ncbi.nlm.nih.gov/11094309/
84 mg/m2 1 times / week multiple, intravenous Highest studied dose\|RP2D Dose: 84 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 84 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/11432625/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/11432625/	DLT: Neutropenia... Other AEs: Neutropenia, Thrombopenia... Dose limiting toxicities: Neutropenia (grade 4, 50%) Other AEs: Neutropenia (grade 3, 50%) Thrombopenia (grade 4, 16.7%) Anemia (grade 3, 16.7%) Diarrhea (grade 4, 16.7%) Vomiting (grade 4, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/11432625/
180 mg/m2 1 times / 3 weeks multiple, intravenous RP2D Dose: 180 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 180 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/11094309/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/11094309/	Other AEs: Neutropenia... Other AEs: Neutropenia (grade 3, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/11094309/

AEs

AE	Significance	Dose	Population
Thrombocytopenia	grade 4, 20%	240 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose Dose: 240 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 240 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/11094309/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/11094309/
Neutropenia	grade 4, 40% DLT	240 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose Dose: 240 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 240 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/11094309/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/11094309/
Anemia	grade 3, 16.7%	84 mg/m2 1 times / week multiple, intravenous Highest studied dose\|RP2D Dose: 84 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 84 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/11432625/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/11432625/
Neutropenia	grade 3, 50%	84 mg/m2 1 times / week multiple, intravenous Highest studied dose\|RP2D Dose: 84 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 84 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/11432625/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/11432625/
Diarrhea	grade 4, 16.7%	84 mg/m2 1 times / week multiple, intravenous Highest studied dose\|RP2D Dose: 84 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 84 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/11432625/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/11432625/
Thrombopenia	grade 4, 16.7%	84 mg/m2 1 times / week multiple, intravenous Highest studied dose\|RP2D Dose: 84 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 84 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/11432625/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/11432625/
Vomiting	grade 4, 16.7%	84 mg/m2 1 times / week multiple, intravenous Highest studied dose\|RP2D Dose: 84 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 84 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/11432625/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/11432625/
Neutropenia	grade 4, 50% DLT	84 mg/m2 1 times / week multiple, intravenous Highest studied dose\|RP2D Dose: 84 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 84 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/11432625/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/11432625/
Neutropenia	grade 3, 33.3%	180 mg/m2 1 times / 3 weeks multiple, intravenous RP2D Dose: 180 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 180 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/11094309/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/11094309/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 1057 BSEP 550 CYP1A2 2153 BCRP 910 P-gp 1741 OCT1 620 OATP1B1 1079 OATP1B3 961 CYP2B6 926	OCT1 393 BCRP 697 P-gp 2052 NAT 3

Drug as perpetrator

Target	Modality	Activity
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/134019#section=BioAssay-Results Page: 5.0	inconclusive [IC50 18.9991 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/pixuvri-epar-public-assessment-report_en.pdf Page: 37.0	likely
OATP1B3 970	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/pixuvri-epar-public-assessment-report_en.pdf Page: 37.0	likely
CYP1A2 2333	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/pixuvri-epar-public-assessment-report_en.pdf Page: 22 \| 39	moderate
CYP2B6 1160	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/pixuvri-epar-public-assessment-report_en.pdf Page: 39.0	no
BCRP 985	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/pixuvri-epar-public-assessment-report_en.pdf Page: 37.0	weak
BSEP 554	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/pixuvri-epar-public-assessment-report_en.pdf Page: 37.0	weak
CYP2C8 1117	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/pixuvri-epar-public-assessment-report_en.pdf Page: 39.0	weak
P-gp 1932	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/pixuvri-epar-public-assessment-report_en.pdf Page: 37.0	weak
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/134019#section=BioAssay-Results Page: 2.0	yes [IC50 1.8999 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/134019#section=BioAssay-Results Page: 2.0	yes [IC50 2.6837 uM]
OCT1 656	inhibitor 4027 Sources: https://www.ema.europa.eu/en/documents/assessment-report/pixuvri-epar-public-assessment-report_en.pdf Page: 37.0	yes

Drug as victim

Target	Modality	Activity
BCRP 697	substrate 4014 Sources: https://www.ema.europa.eu/en/documents/assessment-report/pixuvri-epar-public-assessment-report_en.pdf Page: 36.0	yes
NAT 3	substrate 4014 Sources: https://www.ema.europa.eu/en/documents/assessment-report/pixuvri-epar-public-assessment-report_en.pdf Page: 39.0	yes
OCT1 393	substrate 4014 Sources: https://www.ema.europa.eu/en/documents/assessment-report/pixuvri-epar-public-assessment-report_en.pdf Page: 36.0	yes
P-gp 2052	substrate 4014 Sources: https://www.ema.europa.eu/en/documents/assessment-report/pixuvri-epar-public-assessment-report_en.pdf Page: 22.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.ema.europa.eu/en/documents/assessment-report/pixuvri-epar-public-assessment-report_en.pdf Page: 19.0

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
Phase I study of BBR 2778, a new aza-anthracenedione, in advanced or refractory non-Hodgkin's lymphoma.	2001 May	11432625
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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:57:20 GMT 2025` Edited by `admin` on `Mon Mar 31 17:57:20 GMT 2025`
Record UNII	P0R64C4CR9
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PIXANTRONE DIMALEATE SALT

Preferred Name

English

PIXANTRONE DIMALEATE

Official 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