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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:04:33
Primary Accession Number DB00894
Secondary Accession Number
  • APRD00640
Name Testolactone
Drug Type
  • Approved
  • Small Molecule
Description An antineoplastic agent that is a derivative of progesterone and used to treat advanced breast cancer. [PubChem]
Synonyms
  1. Testolactona [INN-Spanish]
  2. Testolactonum [INN-Latin]
  3. Testolattone [Dcit]
Brand Names
  1. Fludestrin
  2. Teolit
  3. Teslac
  4. Teslak
  5. Testolacton
Brand Mixtures Not Available
Chemical IUPAC Name (4aS,4bR,10aR,10bS,12aS)-10a,12a-dimethyl-4,4a,4b,5,6,10b,11,12-octahydro-3H-naphtho[6,5-f]chromene-2,8-dione
Chemical Formula C19H24O3
Chemical Structure Structure
CAS Registry Number 968-93-4
InChI Identifier InChI=1/C19H24O3/c1-18-9-7-13(20)11-12(18)3-4-14-15(18)8-10-19(2)16(14)5-6-17(21)22-19/h7,9,11,14-16H,3-6,8,10H2,1-2H3/t14-,15+,16+,18+,19+/m1/s1
InChI Key BPEWUONYVDABNZ-DZBHQSCQBA
KEGG Drug D00153 Link Image
KEGG Compound C02197 Link Image
PubChem Compound 13769 Link Image
PubChem Substance 157104 Link Image
ChEBI ID 9460 Link Image
PharmGKB ID PA451626 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] Not Available
RxList Link http://www.rxlist.com/cgi/generic2/testolactone.htm Link Image
PDRhealth Link Not Available
Wikipedia Link Not Available
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 300.3921
Monoisotopic Molecular Weight 300.1725
State Solid
Melting Point 218.5 oC
Experimental Water Solubility Slightly soluble (27.4 mg/L) Source: PhysProp
Predicted Water Solubility 2.30e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 3.7 Source: PhysProp
Predicted LogP 2.33 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.12 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)C=C[C@]34C)[C@@H]1CCC(=O)O2
Canonical SMILES CC12CCC3C(CCC4=CC(=O)C=CC34C)C1CCC(=O)O2
Drug Category
  • Antineoplastic Agents, Hormonal
ATC Codes Not Available
AHFS Codes Not Available
Indication For palliative treatment of advanced breast cancer in postmenopausal women.
Pharmacology Testolactone is a synthetic anti-neoplastic agent that is structurally distinct from the androgen steroid nucleus in possessing a six-membered lactone ring in place of the usual five-membered carbocyclic D-ring. Despite some similarity to testosterone, testolactone has no in vivo androgenic effect. No other hormonal effects have been reported in clinical studies in patients receiving testolactone.
Mechanism of Action Although the precise mechanism by which testolactone produces its clinical antineoplastic effects has not been established, its principal action is reported to be inhibition of steroid aromatase activity and consequent reduction in estrone synthesis from adrenal androstenedione, the major source of estrogen in postmenopausal women. Based on in vitro studies, the aromatase inhibition may be noncompetitive and irreversible. This phenomenon may account for the persistence of testolactone's effect on estrogen synthesis after drug withdrawal.
Absorption Testolactone is well absorbed from the gastrointestinal tract.
Toxicity Oral LD50s in mouse and dog are 1630 mg/kg and 593-926 mg/kg, respectively.
Protein Binding ~85%
Biotransformation Hepatic. Metabolized to several derivatives in the liver, all of which preserve the lactone D-ring.
Half Life Not Available
Dosage Forms
Form Route
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acenocoumarol The androgen, Testolactone, may incrase the anticoagulant effect of the Vitamin K antagonist, Acenocoumarol. Monitor for changes in the therapeutic effect of Acenocoumarol if Testolactone is initiated, discontinued or dose changed.
Cyclosporine The androgen, Testolactone, may increase the hepatotoxicity of Cyclosporine. Testolatone may also elevate serum concentrations of Cyclosporine. Consider alternate therapy or monitor for signs of renal and hepatic toxicity.
Warfarin The androgen, Testolactone, may incrase the anticoagulant effect of the Vitamin K antagonist, Warfarin. Monitor for changes in the therapeutic effect of Warfarin if Testolactone is initiated, discontinued or dose changed.
Food Interactions Not Available
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 19 (Aromatase)
Targets
  1. Cytochrome P450 19A1
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 19 (Aromatase)
Enzyme 1 Gene Name CYP19A1
Enzyme 1 SwissProt ID P11511 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >Cytochrome P450 19 (Aromatase) 
VLEMLNPIHYNITSIVPEAMPAATMPVLLLTGLFLLVWNYEGTSSIPGPGYCMGIGPLIS
HGRFLWMGIGSACNYYNRVYGEFMRVWISGEETLIISKSSSMFHIMKHNHYSSRFGSKLG
LQCIGMHEKGIIFNNNPELWKTTRPFFMKALSGPGLVRMVTVCAESLKTHLDRLEEVTNE
SGYVDVLTLLRRVMLDTSNTLFLRIPLDESAIVVKIQGYFDAWQALLIKPDIFFKISWLY
KKYEKSVKDLKDAIEVLIAEKRRRISTEEKLEECMDFATELILAEKRGDLTRENVNQCIL
EMLIAAPDTMSVSLFFMLFLIAKHPNVEEAIIKEIQTVIGERDIKIDDIQKLKVMENFIY
ESMRYQPVVDLVMRKALEDDVIDGYPVKKGTNIILNIGRMHRLEFFPKPNEFTLENFAKN
VPYRYFQPFGFGPRGCAGKYIAMVMMKAILVTLLRRFHVKTLQGQCVESIQKIHDLSLHP
DETKNMLEMIFTPRNSDRCLEH
Drug Target 1 [top]
Target 1 ID 3811
Target 1 Name Cytochrome P450 19A1
Target 1 Synonyms
  1. Aromatase
  2. CYPXIX
  3. EC 1.14.14.1
  4. Estrogen synthetase
  5. P-450AROM
Target 1 Gene Name CYP19A1
Target 1 Protein Sequence >Cytochrome P450 19A1 
MVLEMLNPIHYNITSIVPEAMPAATMPVLLLTGLFLLVWNYEGTSSIPGPGYCMGIGPLI
SHGRFLWMGIGSACNYYNRVYGEFMRVWISGEETLIISKSSSMFHIMKHNHYSSRFGSKL
GLQCIGMHEKGIIFNNNPELWKTTRPFFMKALSGPGLVRMVTVCAESLKTHLDRLEEVTN
ESGYVDVLTLLRRVMLDTSNTLFLRIPLDESAIVVKIQGYFDAWQALLIKPDIFFKISWL
YKKYEKSVKDLKDAIEVLIAEKRRRISTEEKLEECMDFATELILAEKRGDLTRENVNQCI
LEMLIAAPDTMSVSLFFMLFLIAKHPNVEEAIIKEIQTVIGERDIKIDDIQKLKVMENFI
YESMRYQPVVDLVMRKALEDDVIDGYPVKKGTNIILNIGRMHRLEFFPKPNEFTLENFAK
NVPYRYFQPFGFGPRGCAGKYIAMVMMKAILVTLLRRFHVKTLQGQCVESIQKIHDLSLH
PDETKNMLEMIFTPRNSDRCLEH
Target 1 Number of Residues 511
Target 1 Molecular Weight 57884
Target 1 Theoretical pI 7.56
Target 1 GO Classification
Function
tetrapyrrole binding
heme binding
binding
ion binding
cation binding
transition metal ion binding
iron ion binding
catalytic activity
oxidoreductase activity
monooxygenase activity
Process
physiological process
metabolism
cellular metabolism
generation of precursor metabolites and energy
electron transport
Component
Not Available
Target 1 General Function Secondary metabolites biosynthesis, transport and catabolism
Target 1 Specific Function Catalyzes the formation of aromatic C18 estrogens from C19 androgens
Target 1 Pathways
Name SMPDB Link KEGG Link
Fatty acid metabolism SMP00051 Link Image map00071 Link Image
Target 1 Reactions
  • RH + reduced flavoprotein + O2 = ROH + oxidized flavoprotein + H2O
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 179002 Link Image
Target 1 UniProtKB/Swiss-Prot ID P11511 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name CP19A_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • peripheral membrane protein
Target 1 Gene Sequence >1512 bp 
ATGGTTTTGGAAATGCTGAACCCGATACATTATAACATCACCAGCATCGTGCCTGAAGCC
ATGCCTGCTGCCACCATGCCAGTCCTGCTCCTCACTGGCCTTTTTCTCTTGGTGTGGAAT
TATGAGGGCACATCCTCAATACCAGGTCCTGGCTACTGCATGGGAATTGGACCCCTCATC
TCCCACGGCAGATTCCTGTGGATGGGGATCGGCAGTGCCTGCAACTACTACAACCGGGTA
TATGGAGAATTCATGCGAGTCTGGATCTCTGGAGAGGAAACACTCATTATCAGCAAGTCC
TCAAGTATGTTCCACATAATGAAGCACAATCATTACAGCTCTCGATTCGGCAGCAAACTT
GGGCTGCAGTGCATCGGTATGCATGAGAAAGGCATCATATTTAACAACAATCCAGAGCTC
TGGAAAACAACTCGACCCTTCTTTATGAAAGCTCTGTCAGGCCCCGGCCTTGTTCGTATG
GTCACAGTCTGTGCTGAATCCCTCAAAACACATCTGGACAGGTTGGAGGAGGTGACCAAT
GAATCGGGCTATGTGGACGTGTTGACCCTTCTGCGTCGTGTCATGCTGGACACCTCTAAC
ACGCTCTTCTTGAGGATCCCTTTGGACGAAAGTGCTATCGTGGTTAAAATCCAAGGTTAT
TTTGATGCATGGCAAGCTCTCCTCATCAAACCAGACATCTTCTTTAAGATTTCTTGGCTA
TACAAAAAGTATGAGAAGTCTGTCAAGGATTTGAAAGATGCCATAGAAGTTCTGATAGCA
GAAAAAAGACGCAGGATTTCCACAGAAGAGAAACTGGAAGAATGTATGGACTTTGCCACT
GAGTTGATTTTAGCAGAGAAACGTGGTGACCTGACAAGAGAGAATGTGAACCAGTGCATA
TTGGAAATGCTGATCGCAGCTCCTGACACCATGTCTGTCTCTTTGTTCTTCATGCTATTT
CTCATTGCAAAGCACCCTAATGTTGAAGAGGCAATAATAAAGGAAATCCAGACTGTTATT
GGTGAGAGAGACATAAAGATTGATGATATACAAAAATTAAAAGTGATGGAAAACTTCATT
TATGAGAGCATGCGGTACCAGCCTGTCGTGGACTTGGTCATGCGCAAAGCCTTAGAAGAT
GATGTAATCGATGGCTACCCAGTGAAAAAGGGGACAAACATTATCCTGAATATTGGAAGG
ATGCACAGACTCGAGTTTTTCCCCAAACCCAATGAATTTACTCTTGAAAATTTTGCAAAG
AATGTTCCTTATAGGTACTTTCAGCCATTTGGCTTTGGGCCCCGTGGCTGTGCAGGAAAG
TACATCGCCATGGTGATGATGAAAGCCATCCTCGTTACACTTCTGAGACGATTCCACGTG
AAGACATTGCAAGGACAGTGTGTTGAGAGCATACAGAAGATACACGACTTGTCCTTGCAC
CCAGATGAGACTAAAAACATGCTGGAAATGATCTTTACCCCAAGAAGCTCAGACAGGTGT
CTGGAACACTAG
Target 1 GenBank Gene ID
Target 1 GeneCard ID CYP19A1 Link Image
Target 1 GenAtlas ID CYP19A1 Link Image
Target 1 HGNC ID HGNC:2594 Link Image
Target 1 Chromosome Location 15
Target 1 Locus 15q21.1
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Harada N, Ogawa H, Shozu M, Yamada K, Suhara K, Nishida E, Takagi Y: Biochemical and molecular genetic analyses on placental aromatase (P-450AROM) deficiency. J Biol Chem. 1992 Mar 5;267(7):4781-5. [PubMed Link Image]
  2. Mahendroo MS, Means GD, Mendelson CR, Simpson ER: Tissue-specific expression of human P-450AROM. The promoter responsible for expression in adipose tissue is different from that utilized in placenta. J Biol Chem. 1991 Jun 15;266(17):11276-81. [PubMed Link Image]
  3. Toda K, Terashima M, Mitsuuchi Y, Yamasaki Y, Yokoyama Y, Nojima S, Ushiro H, Maeda T, Yamamoto Y, Sagara Y, et al.: Alternative usage of different poly(A) addition signals for two major species of mRNA encoding human aromatase P-450. FEBS Lett. 1989 Apr 24;247(2):371-6. [PubMed Link Image]
  4. Pompon D, Liu RY, Besman MJ, Wang PL, Shively JE, Chen S: Expression of human placental aromatase in Saccharomyces cerevisiae. Mol Endocrinol. 1989 Sep;3(9):1477-87. [PubMed Link Image]
  5. Means GD, Mahendroo MS, Corbin CJ, Mathis JM, Powell FE, Mendelson CR, Simpson ER: Structural analysis of the gene encoding human aromatase cytochrome P-450, the enzyme responsible for estrogen biosynthesis. J Biol Chem. 1989 Nov 15;264(32):19385-91. [PubMed Link Image]
  6. Corbin CJ, Graham-Lorence S, McPhaul M, Mason JI, Mendelson CR, Simpson ER: Isolation of a full-length cDNA insert encoding human aromatase system cytochrome P-450 and its expression in nonsteroidogenic cells. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8948-52. [PubMed Link Image]
  7. Harada N: Cloning of a complete cDNA encoding human aromatase: immunochemical identification and sequence analysis. Biochem Biophys Res Commun. 1988 Oct 31;156(2):725-32. [PubMed Link Image]
  8. Evans CT, Ledesma DB, Schulz TZ, Simpson ER, Mendelson CR: Isolation and characterization of a complementary DNA specific for human aromatase-system cytochrome P-450 mRNA. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6387-91. [PubMed Link Image]
  9. Chen SA, Besman MJ, Sparkes RS, Zollman S, Klisak I, Mohandas T, Hall PF, Shively JE: Human aromatase: cDNA cloning, Southern blot analysis, and assignment of the gene to chromosome 15. DNA. 1988 Jan-Feb;7(1):27-38. [PubMed Link Image]
  10. Simpson ER, Evans CT, Corbin CJ, Powell FE, Ledesma DB, Mendelson CR: Sequencing of cDNA inserts encoding aromatase cytochrome P-450 (P-450AROM). Mol Cell Endocrinol. 1987 Aug;52(3):267-72. [PubMed Link Image]
  11. 3964273 Chen S, Shively JE, Nakajin S, Shinoda M, Hall PF: Amino terminal sequence analysis of human placenta aromatase. Biochem Biophys Res Commun. 1986 Mar 28;135(3):713-9.
  12. 7690033 Mahendroo MS, Mendelson CR, Simpson ER: Tissue-specific and hormonally controlled alternative promoters regulate aromatase cytochrome P450 gene expression in human adipose tissue. J Biol Chem. 1993 Sep 15;268(26):19463-70.
  13. 8117272 Honda S, Harada N, Takagi Y: Novel exon 1 of the aromatase gene specific for aromatase transcripts in human brain. Biochem Biophys Res Commun. 1994 Feb 15;198(3):1153-60.
  14. 8265607 Ito Y, Fisher CR, Conte FA, Grumbach MM, Simpson ER: Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11673-7.
  15. 8530621 Morishima A, Grumbach MM, Simpson ER, Fisher C, Qin K: Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab. 1995 Dec;80(12):3689-98.
  16. 9211678 Carani C, Qin K, Simoni M, Faustini-Fustini M, Serpente S, Boyd J, Korach KS, Simpson ER: Effect of testosterone and estradiol in a man with aromatase deficiency. N Engl J Med. 1997 Jul 10;337(2):91-5.
Target 1 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]

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