VOSAROXIN


Synonyms	AG-7352 SNS-595 SPC-595 Voreloxin Vosaroxin
Status
Molecule Category	UNKNOWN
ATC	L01XX53
UNII	K6A90IIZ19


Active Pharmaceutical Ingredients Bioactive chemicals	Exact Similarity SubStructure	Threshold (%) >= 70

Structure


InChI Key	XZAFZXJXZHRNAQ-STQMWFEESA-N
Smiles	CN[C@H]1CN(c2ccc3c(=O)c(C(=O)O)cn(-c4nccs4)c3n2)C[C@@H]1OC
InChI	InChI=1S/C18H19N5O4S/c1-19-12-8-22(9-13(12)27-2)14-4-3-10-15(24)11(17(25)26)7-23(16(10)21-14)18-20-5-6-28-18/h3-7,12-13,19H,8-9H2,1-2H3,(H,25,26)/t12-,13-/m0/s1

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C18H19N5O4S
Molecular Weight	401.45
AlogP	0.96
Hydrogen Bond Acceptor	9.0
Hydrogen Bond Donor	2.0
Number of Rotational Bond	5.0
Polar Surface Area	109.58
Molecular species	ZWITTERION
Aromatic Rings	3.0
Heavy Atoms	28.0

Bioactivity

Mechanism of Action	Action	Reference
DNA inhibitor	INHIBITOR	PubMed

Query Gene : ENSG00000131747

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-alpha

Organism : Homo sapiens

Query Gene : ENSG00000131747

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-alpha

Organism : Homo sapiens

Query Gene : ENSG00000131747

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-alpha

Organism : Homo sapiens

Query Gene : ENSG00000131747

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-alpha

Organism : Homo sapiens

Query Gene : ENSG00000131747

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-alpha

Organism : Homo sapiens

Query Gene : ENSG00000131747

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-alpha

Organism : Homo sapiens

Query Gene : ENSG00000131747

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-alpha

Organism : Homo sapiens

Query Gene : ENSG00000131747

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-alpha

Organism : Homo sapiens

Query Gene : ENSG00000131747

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-alpha

Organism : Homo sapiens

Query Gene : ENSG00000131747

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-alpha

Organism : Homo sapiens

Query Gene : ENSG00000131747

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-alpha

Organism : Homo sapiens

Query Gene : ENSG00000131747

Target Name : DNA topoisomerase II

Organism : Homo sapiens

Query Gene : ENSG00000077097

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-beta

Organism : Homo sapiens

Query Gene : ENSG00000077097

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-beta

Organism : Homo sapiens

Query Gene : ENSG00000077097

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-beta

Organism : Homo sapiens

Query Gene : ENSG00000077097

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-beta

Organism : Homo sapiens

Query Gene : ENSG00000077097

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-beta

Organism : Homo sapiens

Query Gene : ENSG00000077097

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-beta

Organism : Homo sapiens

Query Gene : ENSG00000077097

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-beta

Organism : Homo sapiens

Query Gene : ENSG00000077097

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-beta

Organism : Homo sapiens

Query Gene : ENSG00000077097

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-beta

Organism : Homo sapiens

Query Gene : ENSG00000077097

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-beta

Organism : Homo sapiens

Query Gene : ENSG00000077097

Protein : DNA topoisomerase II

Description: DNA topoisomerase 2-beta

Organism : Homo sapiens

Query Gene : ENSG00000077097

Target Name : DNA topoisomerase II

Organism : Homo sapiens


Protein: DNA topoisomerase II Description: DNA topoisomerase 2-alpha Organism : Homo sapiens P11388 ENSG00000131747











Protein: DNA topoisomerase II Description: DNA topoisomerase 2-beta Organism : Homo sapiens Q02880 ENSG00000077097

Reference

Journal : J. Med. Chem.

Title : Synthesis and structure-activity relationships of novel 7-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids as antitumor agents. Part 2.

PubMed ID : 15056007

DOI : 10.1021/jm0304966

Year : 2004

Volume : 47

Issue : 8

First Page : 2097

Last Page : 2109

Authors : Tsuzuki Y, Tomita K, Shibamori K, Sato Y, Kashimoto S, Chiba K.

Abstract : We have previously reported that a series of 7-substituted 6-fluoro-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids possess moderate cytotoxic activity. In a further attempt to find clinically useful antitumor agents, we investigated the structure-activity relationships (SARs) of a new series of compounds obtained by changing the C-6 position of the fluorine atom in addition to the C-5 and C-7 positions and evaluating their cytotoxic activity against several murine and human tumor cell lines. Our results showed that the 6-unsubstituted 1,8-naphthyridine structure had the most potent cytotoxic activity against murine P388 leukemia twice that of the 6-fluoro analogue. In addition, introduction of an amino group at the C-5 position did not have any substantial effect on the cytotoxic activity, while both the 5-chloro and 5-trifluoromethyl groups decreased the cytotoxic activity by 5- to 10-fold. Moreover, aminopyrrolidine derivatives at the C-7 position showed more potent cytotoxic activity than other amines or carbon derivatives. Among the 7-(3-aminopyrrolidinyl) derivatives, the trans-3-methoxy-4-methylaminopyrrolidinyl derivative (27l) was determined to have potent cytotoxic activity in both in vitro and in vivo assays and high water solubility. Finally, the (S,S)-isomer (AG-7352, 3) of 27l, with a cytotoxic activity against human tumor cell lines more potent than that of etoposide, was selected for further development.

Reference

Journal : J. Med. Chem.

Title : Synthesis and structure-activity relationships of novel 7-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids as antitumor agents. Part 2.

PubMed ID : 15056007

DOI : 10.1021/jm0304966

Year : 2004

Volume : 47

Issue : 8

First Page : 2097

Last Page : 2109

Authors : Tsuzuki Y, Tomita K, Shibamori K, Sato Y, Kashimoto S, Chiba K.

Reference

Journal : J. Med. Chem.

Title : Synthesis and structure-activity relationships of novel 7-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids as antitumor agents. Part 2.

PubMed ID : 15056007

DOI : 10.1021/jm0304966

Year : 2004

Volume : 47

Issue : 8

First Page : 2097

Last Page : 2109

Authors : Tsuzuki Y, Tomita K, Shibamori K, Sato Y, Kashimoto S, Chiba K.

Reference

Journal : J. Med. Chem.

Title : Synthesis and structure-activity relationships of novel 7-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids as antitumor agents. Part 2.

PubMed ID : 15056007

DOI : 10.1021/jm0304966

Year : 2004

Volume : 47

Issue : 8

First Page : 2097

Last Page : 2109

Authors : Tsuzuki Y, Tomita K, Shibamori K, Sato Y, Kashimoto S, Chiba K.

Reference

Journal : J. Med. Chem.

Title : Synthesis and structure-activity relationships of novel 7-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids as antitumor agents. Part 2.

PubMed ID : 15056007

DOI : 10.1021/jm0304966

Year : 2004

Volume : 47

Issue : 8

First Page : 2097

Last Page : 2109

Authors : Tsuzuki Y, Tomita K, Shibamori K, Sato Y, Kashimoto S, Chiba K.

Reference

Journal : J. Med. Chem.

Title : Synthesis and structure-activity relationships of novel 7-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids as antitumor agents. Part 2.

PubMed ID : 15056007

DOI : 10.1021/jm0304966

Year : 2004

Volume : 47

Issue : 8

First Page : 2097

Last Page : 2109

Authors : Tsuzuki Y, Tomita K, Shibamori K, Sato Y, Kashimoto S, Chiba K.

Assay Description	Organism	Bioactivity
Cytotoxic activity against human tumor HL-60 leukemia cells	Homo sapiens	0.0498 ug.mL-1
Cytotoxic activity against human tumor Hs 746.T stomach cells	Homo sapiens	0.194 ug.mL-1
Cytotoxic activity against human tumor PANC-1 pancreas cells	Homo sapiens	0.388 ug.mL-1
Cytotoxic activity against human tumor SBC-3 lung cells	Homo sapiens	0.0319 ug.mL-1
Cytotoxic activity against human tumor SCaBER bladder cells	Homo sapiens	0.121 ug.mL-1
Cytotoxic activity against human tumor SK-OV-3 ovary cells	Homo sapiens	0.266 ug.mL-1

Cross References

Resources	Reference
ChEMBL	CHEMBL68117
DrugBank	DB11999
FDA SRS	K6A90IIZ19
PubChem	9952884
SureChEMBL	SCHEMBL674441
ZINC	ZINC000026186622

CONTENTS

Structure
Chemical and Physical Properties
Pharmacology