|Accession Number||DB00894 (APRD00640)|
An antineoplastic agent that is a derivative of progesterone and used to treat advanced breast cancer.
|External IDs||NSC-23759 / SQ 9538 / SQ-9538|
|Product Ingredients||Not Available|
|Approved Prescription Products||Not Available|
|Approved Generic Prescription Products||Not Available|
|Approved Over the Counter Products||Not Available|
|Unapproved/Other Products||Not Available|
|Brand mixtures||Not Available|
|Weight||Average: 300.3921 |
For palliative treatment of advanced breast cancer in postmenopausal women.
|Structured Indications||Not Available|
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.
Testolactone is well absorbed from the gastrointestinal tract.
|Volume of distribution||Not Available|
Hepatic. Metabolized to several derivatives in the liver, all of which preserve the lactone D-ring.
|Route of elimination|
No 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 life||Not Available|
Oral LD50s in mouse and dog are 1630 mg/kg and 593-926 mg/kg, respectively.
|Pharmacogenomic Effects/ADRs||Not Available|
|Food Interactions||Not Available|
Ivan Gilbert, Michael White, "Fermentation method for the preparation of testolactone by fusarium species." U.S. Patent US20060292666, issued December 28, 2006.US20060292666
|General References||Not Available|
|ATC Codes||Not Available|
|AHFS Codes||Not Available|
|PDB Entries||Not Available|
|FDA label||Download (105 KB)|
|MSDS||Download (58.6 KB)|
|Dosage forms||Not Available|
|Predicted ADMET features|
|Mass Spec (NIST)||Not Available|
|Description||This 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.|
|Super Class||Organoheterocyclic compounds|
|Sub Class||Not Available|
|Alternative Parents||Naphthalenes / Delta valerolactones / Pyrans / Oxanes / Cyclic ketones / Carboxylic acid esters / Oxacyclic compounds / Monocarboxylic acids and derivatives / Organic oxides / Hydrocarbon derivatives|
|Substituents||Naphthopyran / Naphthalene / Delta valerolactone / Delta_valerolactone / Pyran / Oxane / Cyclic ketone / Lactone / Ketone / Carboxylic acid ester|
|Molecular Framework||Aliphatic heteropolycyclic compounds|
|External Descriptors||3-oxo-Delta(1),Delta(4)-steroid, seco-androstane (CHEBI:9460 ) / Androstane and derivatives (C02197 ) / C19 steroids (androgens) and derivatives (LMST02020084 )|
- Pharmacological action
- General Function:
- Oxygen binding
- Specific Function:
- Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
- Gene Name:
- Uniprot ID:
- Molecular Weight:
- 57882.48 Da
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
- Raman JD, Schlegel PN: Aromatase inhibitors for male infertility. J Urol. 2002 Feb;167(2 Pt 1):624-9. [PubMed:11792932 ]
- 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 ]
- Dunkel L: Use of aromatase inhibitors to increase final height. Mol Cell Endocrinol. 2006 Jul 25;254-255:207-16. [PubMed:16766117 ]
- 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 ]