T3DB: Doxorubicin

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (14)XML

Targets (14)

Record Information

Version

2.0

Creation Date

2009-07-21 20:28:08 UTC

Update Date

2014-12-24 20:25:54 UTC

Accession Number

T3D2953

Identification

Common Name

Doxorubicin

Class

Small Molecule

Description

Doxorubicin is only found in individuals that have used or taken this drug. It is antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of daunorubicin. [PubChem]Doxorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Doxorubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes.

Compound Type

Amine
Antibiotic
Antibiotic, Antineoplastic
Antineoplastic Agent
Drug
Ester
Ether
Metabolite
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(1S,3S)-3-Glycoloyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranoside
(8S-cis)-10-((3-amino-2,3,6-Trideoxy-alpha-L-lyxo-hexopyranosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-5,12-naphthacenedione
14-hydroxydaunomycin
14-hydroxydaunorubicine
Adriablastina
Adriamycin
Adriblastin
Caelyx
Doxil
Doxorubicine
Doxorubicinum
Hydroxydaunorubicin
Myocet
Rubex

Chemical Formula

C₂₇H₂₉NO₁₁

Average Molecular Mass

543.519 g/mol

Monoisotopic Mass

543.174 g/mol

CAS Registry Number

23214-92-8

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

Traditional Name

doxorubicin

SMILES

[H][C@]1(N)C[C@]([H])(O[C@@]2([H])C[C@@](O)(CC3=C(O)C4=C(C(O)=C23)C(=O)C2=C(C=CC=C2OC)C4=O)C(=O)CO)O[C@@]([H])(C)[C@@]1([H])O

InChI Identifier

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

InChI Key

InChIKey=AOJJSUZBOXZQNB-TZSSRYMLSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as gamma amino acids and derivatives. These are amino acids having a (-NH2) group attached to the gamma carbon atom.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Gamma amino acids and derivatives

Alternative Parents

Substituents

Gamma amino acid or derivatives
Amino fatty acid
Fatty acyl
Amino acid
Carboxylic acid
Monocarboxylic acid or derivatives
Organopnictogen compound
Primary amine
Organooxygen compound
Organonitrogen compound
Amine
Primary aliphatic amine
Organic oxygen compound
Carbonyl group
Organic nitrogen compound
Hydrocarbon derivative
Organic oxide
Aliphatic homomonocyclic compound

Molecular Framework

Aliphatic homomonocyclic compounds

External Descriptors

gamma-amino acid (CHEBI:42797 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	229-231°C
Boiling Point	Not Available
Solubility	Soluble
LogP	1.27

Predicted Properties

Property	Value	Source
Water Solubility	1.18 g/L	ALOGPS
logP	1.41	ALOGPS
logP	0.92	ChemAxon
logS	-2.7	ALOGPS
pKa (Strongest Acidic)	9.53	ChemAxon
pKa (Strongest Basic)	8.94	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	12	ChemAxon
Hydrogen Donor Count	6	ChemAxon
Polar Surface Area	206.07 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	134.59 m³·mol⁻¹	ChemAxon
Polarizability	53.87 Å³	ChemAxon
Number of Rings	5	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a4i-9100210000-2b807cbc2c92b3239ce2	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positive	splash10-0fl0-4910224000-4bfde6a587c553084e35	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_4) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_5) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_6) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_7) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_2) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_3) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_4) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_5) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_6) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_7) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_8) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_9) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_10) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_11) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_12) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_13) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_14) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_15) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_16) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_17) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-006t-0109000000-ac65f689e3fa439adddc	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-006t-0109000000-ac65f689e3fa439adddc	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Positive	splash10-03k9-0309000000-868891bb4c99d599c284	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Negative	splash10-0002-0009000000-5b676bfe14711ba000d6	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-00ov-0005390000-f948ee4b89881c04094f	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00l2-1319310000-6809908c73812c7294b0	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0pea-4109100000-aa6428ee7c0e41ed2d97	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-01ox-0002390000-1d86ac1de2afc3f4ce0d	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-08fv-5209740000-2da58c964c8e55c74f5e	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-08fr-7207900000-9dd3041a50cddfad58dc	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-004j-0409070000-1f754ac056625a678f5e	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-01u1-2619140000-93871ebd236804cb7e03	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-03e9-4910200000-64c8902380be8a1fd183	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-000t-0009000000-c2261d7295031ec8b1a3	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-00kr-0009000000-c0d23b7b41211d5bcf7d	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-1009230000-adab49e4224b716b7c2f	2021-10-11	View Spectrum

Toxicity Profile

Route of Exposure

Parenteral (intravenous)

Mechanism of Toxicity

Doxorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Doxorubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes.

Metabolism

Doxorubicin is capable of undergoing 3 metabolic routes: one-electron reduction, two-electron reduction, and deglycosidation. However, approximately half of the dose is eliminated from the body unchanged. Two electron reduction yields doxorubicinol, a secondary alcohol. This pathway is considered the primary metabolic pathway. The one electron reduction is facilitated by several oxidoreductases to form a doxirubicin-semiquinone radical. These enzymes include mitochondrial and cystolic NADPH dehydrogenates, xanthine oxidase, and nitric oxide synthases. Deglycosidation is a minor metabolic pathway (1-2% of the dose undergoes this pathway). The resultant metabolites are deoxyaglycone or hydroxyaglycone formed via reduction or hydrolysis respectively. Enzymes that may be involved with this pathway include xanthine oxidase, NADPH-cytochrome P450 reductase, and cytosolic NADPH dehydrogenase. Route of Elimination: 40% of the dose appears in bile in 5 days. 5-12% of the drug and its metabolites appears in urine during the same time period. <3% of the dose recovered in urine was doxorubicinol. Half Life: Terminal half life = 20 - 48 hours.

Toxicity Values

LD50: 21 800 ug/kg (Subcutaneous, Rat) (6)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

2A, probably carcinogenic to humans. (11)

Uses/Sources

Doxorubicin is used to produce regression in disseminated neoplastic conditions like acute lymphoblastic leukemia, acute myeloblastic leukemia, Wilms' tumor, neuroblastoma, soft tissue and bone sarcomas, breast carcinoma, ovarian carcinoma, transitional cell bladder carcinoma, thyroid carcinoma, gastric carcinoma, Hodgkin's disease, malignant lymphoma and bronchogenic carcinoma in which the small cell histologic type is the most responsive compared to other cell types. Doxorubicin is also indicated for use as a component of adjuvant therapy in women with evidence of axillary lymph node involvement following resection of primary breast cancer.

Minimum Risk Level

Not Available

Health Effects

Antibiotic resistance

Symptoms

The most common side effects from antibiotics are diarrhea, nausea, vomiting. Fungal infections of the mouth, digestive tract and vagina can also occur with antibiotics

Treatment

Treatment of acute overdosage consists of treatment of the severely myelosuppressed patient with hospitalization, antibiotics, platelet and granulocyte transfusions, and symptomatic treatment of mucositis. (10)

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

28748

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Doxorubicin

PDB ID

DM2

ACToR ID

Not Available

Wikipedia Link

Doxorubicin

References

Synthesis Reference

Gian P. Vicario, Sergio Penco, Federico Arcamone, “Daunorubicin and doxorubicin labelled with .sup.14 C at the 14-position and processes for their preparation.” U.S. Patent US4211864, issued March, 1976.

MSDS

Link

General References

Weiss RB: The anthracyclines: will we ever find a better doxorubicin? Semin Oncol. 1992 Dec;19(6):670-86. [1462166 ]
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. [4290058 ]
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. [5365804 ]
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. [5772652 ]
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. [9864344 ]
Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Mordente A, Meucci E, Silvestrini A, Martorana GE, Giardina B: New developments in anthracycline-induced cardiotoxicity. Curr Med Chem. 2009;16(13):1656-72. [19442138 ]
Minotti G: Reactions of adriamycin with microsomal iron and lipids. Free Radic Res Commun. 1989;7(3-6):143-8. [2555273 ]
Drugs.com [Link]
RxList: The Internet Drug Index (2009). [Link]
International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]

Gene Regulation

Up-Regulated Genes

Gene	Gene Symbol	Gene ID	Interaction	Chromosome	Details

Down-Regulated Genes

Gene	Gene Symbol	Gene ID	Interaction	Chromosome	Details

Targets

Target Details

1. DNA topoisomerase 2-alpha

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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	1 uM	Not Available	BindingDB 22984

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Rody A, Karn T, Gatje R, Ahr A, Solbach C, Kourtis K, Munnes M, Loibl S, Kissler S, Ruckhaberle E, Holtrich U, von Minckwitz G, Kaufmann M: Gene expression profiling of breast cancer patients treated with docetaxel, doxorubicin, and cyclophosphamide within the GEPARTRIO trial: HER-2, but not topoisomerase II alpha and microtubule-associated protein tau, is highly predictive of tumor response. Breast. 2007 Feb;16(1):86-93. Epub 2006 Sep 28. [17010609 ]
Koehn H, Magan N, Isaacs RJ, Stowell KM: Differential regulation of DNA repair protein Rad51 in human tumour cell lines exposed to doxorubicin. Anticancer Drugs. 2007 Apr;18(4):419-25. [17351394 ]
Hayashi S, Hatashita M, Matsumoto H, Shioura H, Kitai R, Kano E: Enhancement of radiosensitivity by topoisomerase II inhibitor, amrubicin and amrubicinol, in human lung adenocarcinoma A549 cells and kinetics of apoptosis and necrosis induction. Int J Mol Med. 2006 Nov;18(5):909-15. [17016621 ]
Azarova AM, Lyu YL, Lin CP, Tsai YC, Lau JY, Wang JC, Liu LF: Roles of DNA topoisomerase II isozymes in chemotherapy and secondary malignancies. Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11014-9. Epub 2007 Jun 19. [17578914 ]
Menendez JA, Vellon L, Lupu R: DNA topoisomerase IIalpha (TOP2A) inhibitors up-regulate fatty acid synthase gene expression in SK-Br3 breast cancer cells: in vitro evidence for a 'functional amplicon' involving FAS, Her-2/neu and TOP2A genes. Int J Mol Med. 2006 Dec;18(6):1081-7. [17089011 ]
Suzuki K, Yahara S, Maehata K, Uyeda M: Isoaurostatin, a novel topoisomerase inhibitor produced by Thermomonospora alba. J Nat Prod. 2001 Feb;64(2):204-7. [11430001 ]

2. DNA

General Function:: Used for biological information storage.
Specific Function:: DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:: 2.15 x 10¹² Da

References

Fornari FA, Randolph JK, Yalowich JC, Ritke MK, Gewirtz DA: Interference by doxorubicin with DNA unwinding in MCF-7 breast tumor cells. Mol Pharmacol. 1994 Apr;45(4):649-56. [8183243 ]
Momparler RL, Karon M, Siegel SE, Avila F: Effect of adriamycin on DNA, RNA, and protein synthesis in cell-free systems and intact cells. Cancer Res. 1976 Aug;36(8):2891-5. [1277199 ]
Frederick CA, Williams LD, Ughetto G, van der Marel GA, van Boom JH, Rich A, Wang AH: Structural comparison of anticancer drug-DNA complexes: adriamycin and daunomycin. Biochemistry. 1990 Mar 13;29(10):2538-49. [2334681 ]

Target Details

3. DNA topoisomerase 1

General Function:: Poly(a) rna binding
Specific Function:: Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component ARNTL/BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the ARNTL/BMAL1 promoter.
Gene Name:: TOP1
Uniprot ID:: P11387
Molecular Weight:: 90725.19 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	20 uM	Not Available	BindingDB 22984
IC50	>200 uM	Not Available	BindingDB 22984

References

Tseng CH, Tzeng CC, Yang CL, Lu PJ, Chen HL, Li HY, Chuang YC, Yang CN, Chen YL: Synthesis and antiproliferative evaluation of certain indeno[1,2-c]quinoline derivatives. Part 2. J Med Chem. 2010 Aug 26;53(16):6164-79. doi: 10.1021/jm1005447. [20662543 ]
Suzuki K, Yahara S, Maehata K, Uyeda M: Isoaurostatin, a novel topoisomerase inhibitor produced by Thermomonospora alba. J Nat Prod. 2001 Feb;64(2):204-7. [11430001 ]

Target Details

4. 7-dehydrocholesterol reductase

General Function:: 7-dehydrocholesterol reductase activity
Specific Function:: Production of cholesterol by reduction of C7-C8 double bond of 7-dehydrocholesterol (7-DHC).
Gene Name:: DHCR7
Uniprot ID:: Q9UBM7
Molecular Weight:: 54488.98 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	0.15 uM	Not Available	BindingDB 22984
IC50	0.2 uM	Not Available	BindingDB 22984
IC50	0.3 uM	Not Available	BindingDB 22984
IC50	10 uM	Not Available	BindingDB 22984

References

Burke PJ, Kalet BT, Koch TH: Antiestrogen binding site and estrogen receptor mediate uptake and distribution of 4-hydroxytamoxifen-targeted doxorubicin-formaldehyde conjugate in breast cancer cells. J Med Chem. 2004 Dec 16;47(26):6509-18. [15588086 ]

Target Details

5. 72 kDa type IV collagenase

General Function:: Zinc ion binding
Specific Function:: Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues in association with MMP14.PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels.Isoform 2: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways.
Gene Name:: MMP2
Uniprot ID:: P08253
Molecular Weight:: 73881.695 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	1.1 uM	Not Available	BindingDB 22984

References

Bols M, Binderup L, Hansen J, Rasmussen P: Inhibition of collagenase by aranciamycin and aranciamycin derivatives. J Med Chem. 1992 Jul 24;35(15):2768-71. [1322986 ]

Target Details

6. Aurora kinase A

General Function:: Protein serine/threonine/tyrosine kinase activity
Specific Function:: Mitotic serine/threonine kinases that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin depolymerase activity. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Important for microtubule formation and/or stabilization. Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and stabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Necessary for proper cilia disassembly prior to mitosis.
Gene Name:: AURKA
Uniprot ID:: O14965
Molecular Weight:: 45809.03 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	0.04 uM	Not Available	BindingDB 22984

References

Shaaban MR, Saleh TS, Mayhoub AS, Farag AM: Single step synthesis of new fused pyrimidine derivatives and their evaluation as potent Aurora-A kinase inhibitors. Eur J Med Chem. 2011 Sep;46(9):3690-5. doi: 10.1016/j.ejmech.2011.05.033. Epub 2011 May 20. [21664013 ]

Target Details

7. Fas-binding factor 1

General Function:: Not Available
Specific Function:: Keratin-binding protein required for epithelial cell polarization. Involved in apical junction complex (AJC) assembly via its interaction with PARD3. Required for ciliogenesis.
Gene Name:: FBF1
Uniprot ID:: Q8TES7
Molecular Weight:: 125445.19 Da

References

Schmid B, Chung DE, Warnecke A, Fichtner I, Kratz F: Albumin-binding prodrugs of camptothecin and doxorubicin with an Ala-Leu-Ala-Leu-linker that are cleaved by cathepsin B: synthesis and antitumor efficacy. Bioconjug Chem. 2007 May-Jun;18(3):702-16. Epub 2007 Mar 23. [17378599 ]

Target Details

8. Multidrug resistance-associated protein 1

General Function:: Transporter activity
Specific Function:: Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency.
Gene Name:: ABCC1
Uniprot ID:: P33527
Molecular Weight:: 171589.5 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	50 uM	Not Available	BindingDB 22984

References

Loe DW, Almquist KC, Cole SP, Deeley RG: ATP-dependent 17 beta-estradiol 17-(beta-D-glucuronide) transport by multidrug resistance protein (MRP). Inhibition by cholestatic steroids. J Biol Chem. 1996 Apr 19;271(16):9683-9. [8621644 ]

Target Details

9. Nucleolar and coiled-body phosphoprotein 1

General Function:: Poly(a) rna binding
Specific Function:: Related to nucleologenesis, may play a role in the maintenance of the fundamental structure of the fibrillar center and dense fibrillar component in the nucleolus. It has intrinsic GTPase and ATPase activities. May play an important role in transcription catalyzed by RNA polymerase I.
Gene Name:: NOLC1
Uniprot ID:: Q14978
Molecular Weight:: 73602.49 Da

References

Kim YK, Lee WK, Jin Y, Lee KJ, Jeon H, Yu YG: Doxorubicin binds to un-phosphorylated form of hNopp140 and reduces protein kinase CK2-dependent phosphorylation of hNopp140. J Biochem Mol Biol. 2006 Nov 30;39(6):774-81. [17129415 ]

Target Details

10. P2Y purinoceptor 12

General Function:: Guanyl-nucleotide exchange factor activity
Specific Function:: Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation.
Gene Name:: P2RY12
Uniprot ID:: Q9H244
Molecular Weight:: 39438.355 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	>10 uM	Not Available	BindingDB 22984

References

Baqi Y, Atzler K, Kose M, Glanzel M, Muller CE: High-affinity, non-nucleotide-derived competitive antagonists of platelet P2Y12 receptors. J Med Chem. 2009 Jun 25;52(12):3784-93. doi: 10.1021/jm9003297. [19463000 ]

Target Details

11. Solute carrier organic anion transporter family member 1B1

General Function:: Sodium-independent organic anion transmembrane transporter activity
Specific Function:: Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:: SLCO1B1
Uniprot ID:: Q9Y6L6
Molecular Weight:: 76447.99 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	150 uM	Not Available	BindingDB 22984
IC50	160 uM	Not Available	BindingDB 22984

References

Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [22541068 ]

Target Details

12. Solute carrier organic anion transporter family member 1B3

General Function:: Sodium-independent organic anion transmembrane transporter activity
Specific Function:: Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP). Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:: SLCO1B3
Uniprot ID:: Q9NPD5
Molecular Weight:: 77402.175 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	38 uM	Not Available	BindingDB 22984
IC50	41 uM	Not Available	BindingDB 22984

References

Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [22541068 ]

Target Details

13. Solute carrier organic anion transporter family member 2B1

General Function:: Sodium-independent organic anion transmembrane transporter activity
Specific Function:: Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name:: SLCO2B1
Uniprot ID:: O94956
Molecular Weight:: 76709.98 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	230 uM	Not Available	BindingDB 22984
IC50	240 uM	Not Available	BindingDB 22984

References

Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [22541068 ]

Target Details

14. Telomerase reverse transcriptase

General Function:: Trna binding
Specific Function:: Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. Active in progenitor and cancer cells. Inactive, or very low activity, in normal somatic cells. Catalytic component of the teleromerase holoenzyme complex whose main activity is the elongation of telomeres by acting as a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme. Catalyzes the RNA-dependent extension of 3'-chromosomal termini with the 6-nucleotide telomeric repeat unit, 5'-TTAGGG-3'. The catalytic cycle involves primer binding, primer extension and release of product once the template boundary has been reached or nascent product translocation followed by further extension. More active on substrates containing 2 or 3 telomeric repeats. Telomerase activity is regulated by a number of factors including telomerase complex-associated proteins, chaperones and polypeptide modifiers. Modulates Wnt signaling. Plays important roles in aging and antiapoptosis.
Gene Name:: TERT
Uniprot ID:: O14746
Molecular Weight:: 126995.435 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	73 uM	Not Available	BindingDB 22984

References

Suzuki K, Yahara S, Maehata K, Uyeda M: Isoaurostatin, a novel topoisomerase inhibitor produced by Thermomonospora alba. J Nat Prod. 2001 Feb;64(2):204-7. [11430001 ]

Doxorubicin (T3D2953)

Structure for T3D2953: Doxorubicin

Targets

Binding/Activity Constants

References

References

Binding/Activity Constants

References

Binding/Activity Constants

References

Binding/Activity Constants

References

Binding/Activity Constants

References

References

Binding/Activity Constants

References

References

Binding/Activity Constants

References

Binding/Activity Constants

References

Binding/Activity Constants

References

Binding/Activity Constants

References

Binding/Activity Constants

References