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Identification
NameTestolactone
Accession NumberDB00894  (APRD00640)
TypeSmall Molecule
GroupsApproved
Description

An antineoplastic agent that is a derivative of progesterone and used to treat advanced breast cancer. [PubChem]

Structure
Thumb
Synonyms
(4AS,4br,10ar,10bs,12as)-10a,12a-dimethyl-3,4,4a,5,6,10a,10b,11,12,12a-decahydro-2H-naphtho[2,1-F]chromene-2,8(4bh)-dione
1-Dehydrotestololactone
1,2-Didehydrotestololactone
13-Hydroxy-3-oxo-13,17-secoandrosta-1,4-dien-17-oic acid delta-lactone
D-Homo-17a-oxaandrosta-1,4-diene-3,17-dione
delta(1)-Testololactone
Teslac
Testolactona
Testolactone
Testolactonum
Testolattone
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
FludestrinBristol-Myers Squibb
TeslacBristol-Myers Squibb
Brand mixturesNot Available
SaltsNot Available
Categories
UNII6J9BLA949Q
CAS number968-93-4
WeightAverage: 300.3921
Monoisotopic: 300.172544634
Chemical FormulaC19H24O3
InChI KeyInChIKey=BPEWUONYVDABNZ-DZBHQSCQSA-N
InChI
InChI=1S/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
IUPAC Name
(1R,2S,7S,10S,11R)-7,11-dimethyl-6-oxatetracyclo[8.8.0.0²,⁷.0¹¹,¹⁶]octadeca-12,15-diene-5,14-dione
SMILES
[H][C@@]12CCC3=CC(=O)C=C[C@]3(C)[C@@]1([H])CC[C@]1(C)OC(=O)CC[C@@]21[H]
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as naphthopyrans. These are compounds containing a pyran ring fused to a naphthalene moiety. Furan is a 6 membered-ring non-aromatic ring with five carbon and one oxygen atoms. Naphthalene is a polycyclic aromatic hydrocarbon made up of two fused benzene rings.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassNaphthopyrans
Sub ClassNot Available
Direct ParentNaphthopyrans
Alternative Parents
Substituents
  • Naphthopyran
  • Naphthalene
  • Delta_valerolactone
  • Delta valerolactone
  • Pyran
  • Oxane
  • Cyclic ketone
  • Lactone
  • Ketone
  • Carboxylic acid ester
  • Oxacycle
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor palliative treatment of advanced breast cancer in postmenopausal women.
PharmacodynamicsTestolactone 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 actionAlthough 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.
Related Articles
AbsorptionTestolactone is well absorbed from the gastrointestinal tract.
Volume of distributionNot Available
Protein binding~85%
Metabolism

Hepatic. Metabolized to several derivatives in the liver, all of which preserve the lactone D-ring.

Route of eliminationNo clinical effects in humans of testolactone on adrenal function have been reported; however, one study noted an increase in urinary excretion of 17-ketosteroids in most of the patients treated with 150 mg/day orally. It is metabolized to several derivatives in the liver, all of which preserve the lactone D-ring. These metabolites, as well as some unmetabolized drug, are excreted in the urine.
Half lifeNot Available
ClearanceNot Available
ToxicityOral LD50s in mouse and dog are 1630 mg/kg and 593-926 mg/kg, respectively.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9945
Blood Brain Barrier+0.9379
Caco-2 permeable+0.7355
P-glycoprotein substrateSubstrate0.6792
P-glycoprotein inhibitor IInhibitor0.6476
P-glycoprotein inhibitor IINon-inhibitor0.6498
Renal organic cation transporterNon-inhibitor0.7565
CYP450 2C9 substrateNon-substrate0.8542
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6459
CYP450 1A2 substrateNon-inhibitor0.7315
CYP450 2C9 inhibitorNon-inhibitor0.8996
CYP450 2D6 inhibitorNon-inhibitor0.9177
CYP450 2C19 inhibitorNon-inhibitor0.8484
CYP450 3A4 inhibitorNon-inhibitor0.7612
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9224
Ames testNon AMES toxic0.9515
CarcinogenicityNon-carcinogens0.9515
BiodegradationNot ready biodegradable0.9096
Rat acute toxicity1.7356 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8719
hERG inhibition (predictor II)Non-inhibitor0.8734
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb
  • Bristol myers squibb co
Packagers
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point218.5 °CPhysProp
water solubilitySlightly soluble (27.4 mg/L)Not Available
logP3.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.023 mg/mLALOGPS
logP2.33ALOGPS
logP3.23ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)18.84ChemAxon
pKa (Strongest Basic)-5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area43.37 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity85.79 m3·mol-1ChemAxon
Polarizability33.42 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

Ivan Gilbert, Michael White, “Fermentation method for the preparation of testolactone by fusarium species.” U.S. Patent US20060292666, issued December 28, 2006.

US20060292666
General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (105 KB)
MSDSDownload (58.6 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Oxygen binding
Specific Function:
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name:
CYP19A1
Uniprot ID:
P11511
Molecular Weight:
57882.48 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Raman JD, Schlegel PN: Aromatase inhibitors for male infertility. J Urol. 2002 Feb;167(2 Pt 1):624-9. [PubMed:11792932 ]
  3. Herzog AG, Klein P, Jacobs AR: Testosterone versus testosterone and testolactone in treating reproductive and sexual dysfunction in men with epilepsy and hypogonadism. Neurology. 1998 Mar;50(3):782-4. [PubMed:9521275 ]
  4. Dunkel L: Use of aromatase inhibitors to increase final height. Mol Cell Endocrinol. 2006 Jul 25;254-255:207-16. [PubMed:16766117 ]
  5. Cepa MM, Tavares da Silva EJ, Correia-da-Silva G, Roleira FM, Teixeira NA: Structure-activity relationships of new A,D-ring modified steroids as aromatase inhibitors: design, synthesis, and biological activity evaluation. J Med Chem. 2005 Oct 6;48(20):6379-85. [PubMed:16190763 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23