FRCD

Common Name	Dexrazoxane(F04751)
2D Structure
Description	An antimitotic agent with immunosuppressive properties. Dexrazoxane, the (+)-enantiomorph of razoxane, provides cardioprotection against anthracycline toxicity. It appears to inhibit formation of a toxic iron-anthracycline complex. The Food and Drug Administration has designated dexrazoxane as an orphan drug for use in the prevention or reduction in the incidence and severity of anthracycline-induced cardiomyopathy.
FRCD ID	F04751
CAS Number	24584-09-6
PubChem CID	71384
Formula	C11H16N4O4
IUPAC Name	4-[(2S)-2-(3,5-dioxopiperazin-1-yl)propyl]piperazine-2,6-dione
InChI Key	BMKDZUISNHGIBY-ZETCQYMHSA-N
InChI	InChI=1S/C11H16N4O4/c1-7(15-5-10(18)13-11(19)6-15)2-14-3-8(16)12-9(17)4-14/h7H,2-6H2,1H3,(H,12,16,17)(H,13,18,19)/t7-/m0/s1
Canonical SMILES	CC(CN1CC(=O)NC(=O)C1)N2CC(=O)NC(=O)C2
Isomeric SMILES	C[C@@H](CN1CC(=O)NC(=O)C1)N2CC(=O)NC(=O)C2
Wikipedia	Dexrazoxane
Synonyms	(S)-4,4'-(Propane-1,2-diyl)bis(piperazine-2,6-dione) Dexrazoxane 24584-09-6 Zinecard ICRF-187 Cardioxane Dexrazoxano Dexrazoxanum Dextrorazoxane Dexrazoxanum [INN-Latin]
Classifies	Predicted: Veterinary Drug
Update Date	Nov 13, 2018 17:07

Kingdom	Organic compounds
Superclass	Organic acids and derivatives
Class	Carboxylic acids and derivatives
Subclass	Amino acids, peptides, and analogues
Intermediate Tree Nodes	Amino acids and derivatives
Direct Parent	Alpha amino acids and derivatives
Alternative Parents	Hydrocarbon derivatives Organic oxides Carbonyl compounds Organopnictogen compounds Azacyclic compounds Trialkylamines N-alkylpiperazines Dicarboximides N-unsubstituted carboxylic acid imides Dioxopiperazines
Molecular Framework	Aliphatic heteromonocyclic compounds
Substituents	Alpha-amino acid or derivatives - Dioxopiperazine - N-alkylpiperazine - 1,4-diazinane - Piperazine - Carboxylic acid imide - Dicarboximide - Carboxylic acid imide, n-unsubstituted - Tertiary aliphatic amine - Tertiary amine - Organoheterocyclic compound - Azacycle - Organic nitrogen compound - Organooxygen compound - Organonitrogen compound - Amine - Organic oxygen compound - Hydrocarbon derivative - Organic oxide - Carbonyl group - Organopnictogen compound - Aliphatic heteromonocyclic compound
Description	This compound belongs to the class of organic compounds known as alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.

Property Name	Property Value
Molecular Weight	268.273
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	3
Complexity	404
Monoisotopic Mass	268.117
Exact Mass	268.117
XLogP	-1.4
Formal Charge	0
Heavy Atom Count	19
Defined Atom Stereocenter Count	1
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Isotope Atom Count	0
Covalently-Bonded Unit Count	1

Model	Result	Probability
Absorption
Blood-Brain Barrier	BBB+	0.6387
Human Intestinal Absorption	HIA+	0.8518
Caco-2 Permeability	Caco2-	0.6144
P-glycoprotein Substrate	Substrate	0.8766
P-glycoprotein Inhibitor	Inhibitor	0.6576
P-glycoprotein Inhibitor	Non-inhibitor	0.9653
Renal Organic Cation Transporter	Non-inhibitor	0.7348
Distribution
Subcellular localization	Lysosome	0.5380
Metabolism
CYP450 2C9 Substrate	Non-substrate	0.8399
CYP450 2D6 Substrate	Non-substrate	0.7872
CYP450 3A4 Substrate	Substrate	0.5139
CYP450 1A2 Inhibitor	Non-inhibitor	0.9458
CYP450 2C9 Inhibitor	Non-inhibitor	0.8828
CYP450 2D6 Inhibitor	Non-inhibitor	0.9348
CYP450 2C19 Inhibitor	Non-inhibitor	0.7777
CYP450 3A4 Inhibitor	Non-inhibitor	0.9666
CYP Inhibitory Promiscuity	Low CYP Inhibitory Promiscuity	0.9741
Excretion
Toxicity
Human Ether-a-go-go-Related Gene Inhibition	Weak inhibitor	0.9410
Human Ether-a-go-go-Related Gene Inhibition	Non-inhibitor	0.8929
AMES Toxicity	Non AMES toxic	0.9132
Carcinogens	Non-carcinogens	0.9077
Fish Toxicity	Low FHMT	0.6662
Tetrahymena Pyriformis Toxicity	High TPT	0.8421
Honey Bee Toxicity	Low HBT	0.8736
Biodegradation	Not ready biodegradable	0.9910
Acute Oral Toxicity	III	0.7343
Carcinogenicity (Three-class)	Warning	0.5287

Model	Value	Unit
Absorption
Aqueous solubility	-2.0191	LogS
Caco-2 Permeability	0.5037	LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity	2.4267	LD50, mol/kg
Fish Toxicity	2.3102	pLC50, mg/L
Tetrahymena Pyriformis Toxicity	0.1128	pIGC50, ug/L

Title	Journal	Date	Pubmed ID
The iron chelator Dp44mT inhibits the proliferation of cancer cells but fails to protect from doxorubicin-induced cardiotoxicity in spontaneously hypertensive rats.	Cancer Chemother Pharmacol	2011 Nov	21373894

Targets

General Function:: Ubiquitin binding
Specific Function:: Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).
Gene Name:: TOP2A
Uniprot ID:: P11388
Molecular Weight:: 174383.88 Da
Mechanism of Action:: The mechanism by which dexrazoxane exerts its cardioprotective activity is not fully understood. Dexrazoxane is a cyclic derivative of EDTA that readily penetrates cell membranes. Results of laboratory studies suggest that dexrazoxane is converted intracellularly to a ring-opened chelating agent that interferes with iron-mediated free radical generation thought to be responsible, in part, for anthracycline-induced cardiomyopathy.

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]

General Function:: Protein kinase c binding
Specific Function:: Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks.
Gene Name:: TOP2B
Uniprot ID:: Q02880
Molecular Weight:: 183265.825 Da

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]