(8S,10S)-10-{[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy}-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-5,7,8,9,10,12-hexahydrotetracene-5,12-dione

• ChemBase ID: 870
• Molecular Formular: C27H29NO11
• Molecular Mass: 543.51926
• Monoisotopic Mass: 543.17406075
• SMILES: O([C@H]1C[C@@](O)(Cc2c1c(O)c1c(c2O)C(=O)c2c(C1=O)c(OC)ccc2)C(=O)CO)[C@@H]1O[C@H]([C@@H](O)[C@@H](N)C1)C
• Canonical SMILES: OCC(=O)[C@@]1(O)C[C@H](O[C@H]2C[C@H](N)[C@@H]([C@@H](O2)C)O)c2c(C1)c(O)c1c(c2O)C(=O)c2c(C1=O)cccc2OC
• InChI: InChI=1S/C27H29NO11/c1-10-22(31)13(28)6-17(38-10)39-15-8-27(36,16(30)9-29)7-12-19(15)26(35)21-20(24(12)33)23(32)11-4-3-5-14(37-2)18(11)25(21)34/h3-5,10,13,15,17,22,29,31,33,35-36H,6-9,28H2,1-2H3/t10-,13-,15-,17-,22+,27-/m0/s1
• InChIKey: AOJJSUZBOXZQNB-TZSSRYMLSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (8S,10S)-10-{[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy}-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-5,7,8,9,10,12-hexahydrotetracene-5,12-dione
• IUPAC Traditional name: doxorubicin
• Brand Name: ADM; Adriablastin; Adriamycin; Adriamycin PFS; Adriamycin RDF; Adriamycin Semiquinone; Adriblastin; Adriblastina; Caelyx; DM2; Doxil; Doxo; RDF Rubex; Rubex; Myocet; Resmycin
• Synonyms: Doxorubicin HCl; Doxorubicin Hydrochloride; Doxorubicina [INN-Spanish]; Doxorubicine [INN-French]; Doxorubicinum [INN-Latin]; doxorubicin; Doxorubicin

Database IDs

• CAS Number: 23214-92-8
• PubChem SID: 160964333; 46507641
• PubChem CID: 31703
• CHEBI ID: 28748
• ATC CODE: L01DB01
• CHEMBL: 179
• Chemspider ID: 29400
• DrugBank ID: DB00997
• KEGG ID: D03899
• Unique Ingredient Identifier: 80168379AG
• Wikipedia Title: Doxorubicin
• Medline Plus: a682221

CALCULATED PROPERTIES

JChem

• Acid pKa: 9.53088
• H Acceptors: 12
• H Donor: 6
• LogD (pH = 5.5): -1.4428744
• LogD (pH = 7.4): -0.27556196
• Log P: 0.91642165
• Molar Refractivity: 134.5937 cm^3
• Polarizability: 52.692078 Å^3
• Polar Surface Area: 206.07 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 1.41
• LOG S: -2.67
• Solubility (Water): 1.18e+00 g/l

PROPERTIES

Physical Property

• Solubility: Soluble
• Hydrophobicity(logP): -0.5

Pharmacology Properties

• Admin Routes: Intravenous
• Bioavailability: 5% (Oral)
• Excretion: Biliary and fecal
• Half Life: 12–18.5 hours when released from liposomes
• Metabolism: CYP3A4
• Legal Status: POM (UK); Rx-only (US)
• Pregnancy Category: D (Australia); D (US)

DETAILS

DrugBank - DB00997

• Drug Groups: approved; investigational
• Description: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of daunorubicin. [PubChem]
• Indication: For the treatment of Koposi's sarcome connected to AIDS.
• Pharmacology: Doxorubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Doxorubicin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin are used exclusively for the treatment of leukemia. Doxorubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Doxorubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific.
• Toxicity: LD₅₀=21800 ug/kg (rat, subcutaneous)
• Affected Organisms: Humans and other mammals
• Half Life: 55 hours
• Protein Binding: 70%
• Elimination: Plasma clearance is in the range 324 to 809 mL/min/m2 and is predominately by metabolism and biliary excretion.
• Clearance: * 324-809 mL/min/m2; * 1088 mL/min/m2 [Men]; * 433 mL/min/m2 [Women]; * 1540 mL/min/m2 [children greater than 2 years of age receiving administration of 10 to 75 mg/m2 doses]; * 813 mL/min/m2 [infants younger than 2 years of age receiving administration of 10 to 75 mg/m2 doses]
• References: Weiss RB: The anthracyclines: will we ever find a better doxorubicin? Semin Oncol. 1992 Dec;19(6):670-86. [Pubmed] ; Tan C, Tasaka H, Yu KP, Murphy ML, Karnofsky DA: Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Clinical evaluation with special reference to childhood leukemia. Cancer. 1967 Mar;20(3):333-53. [Pubmed] ; Arcamone F, Cassinelli G, Fantini G, Grein A, Orezzi P, Pol C, Spalla C: Adriamycin, 14-hydroxydaunomycin, a new antitumor antibiotic from S. peucetius var. caesius. Biotechnol Bioeng. 1969 Nov;11(6):1101-10. [Pubmed] ; Di Marco A, Gaetani M, Scarpinato B: Adriamycin (NSC-123,127): a new antibiotic with antitumor activity. Cancer Chemother Rep. 1969 Feb;53(1):33-7. [Pubmed] ; Lomovskaya N, Otten SL, Doi-Katayama Y, Fonstein L, Liu XC, Takatsu T, Inventi-Solari A, Filippini S, Torti F, Colombo AL, Hutchinson CR: Doxorubicin overproduction in Streptomyces peucetius: cloning and characterization of the dnrU ketoreductase and dnrV genes and the doxA cytochrome P-450 hydroxylase gene. J Bacteriol. 1999 Jan;181(1):305-18. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Tan C, Tasaka H, Yu KP, Murphy ML, Karnofsky DA: Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Clinical evaluation with special reference to childhood leukemia. Cancer. 1967 Mar;20(3):333-53. Pubmed
• Arcamone F, Cassinelli G, Fantini G, Grein A, Orezzi P, Pol C, Spalla C: Adriamycin, 14-hydroxydaunomycin, a new antitumor antibiotic from S. peucetius var. caesius. Biotechnol Bioeng. 1969 Nov;11(6):1101-10. Pubmed
• Di Marco A, Gaetani M, Scarpinato B: Adriamycin (NSC-123,127): a new antibiotic with antitumor activity. Cancer Chemother Rep. 1969 Feb;53(1):33-7. Pubmed
• Lomovskaya N, Otten SL, Doi-Katayama Y, Fonstein L, Liu XC, Takatsu T, Inventi-Solari A, Filippini S, Torti F, Colombo AL, Hutchinson CR: Doxorubicin overproduction in Streptomyces peucetius: cloning and characterization of the dnrU ketoreductase and dnrV genes and the doxA cytochrome P-450 hydroxylase gene. J Bacteriol. 1999 Jan;181(1):305-18. Pubmed
• Weiss RB: The anthracyclines: will we ever find a better doxorubicin? Semin Oncol. 1992 Dec;19(6):670-86. Pubmed