DT-Web

DB00007 - Leuprolide


Identification
Name Leuprolide
Accession Number DB00007 (BIOD00009, BTD00009)
Type biotech
Description Leuprolide belongs to the general class of drugs known as hormones or hormone antagonists. It is a synthetic 9 residue peptide analog of gonadotropin releasing hormone. Leuprolide is used to treat advanced prostate cancer. It is also used to treat uterine fibroids and endometriosis. Leuprolide is also under investigation for possible use in the treatment of mild to moderate Alzheimer's disease.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 1209.3983
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication For treatment of prostate cancer, endometriosis, uterine fibroids and premature puberty
Mechanism of action Leuprolide binds to the gonadotropin releasing hormone receptor and acts as a potent inhibitor of gonadotropin secretion.
Absorption Bioavailability by subcutaneous administration is comparable to that by intravenous administration.
Protein binding 43% to 49%
Biotransformation Primarily degraded by peptidase and not by cytochrome P450 enzymes.
Route of elimination Excretion in urine
Toxicity In rats subcutaneous administration of 250 to 500 times the recommended human dose, expressed on a per body weight basis, resulted in dyspnea, decreased activity, and local irritation at the injection site. There is no evidence at present that there is a clinical counterpart of this phenomenon. In early clinical trials with leuprolide acetate doses as high as 20 mg/day for up to two years caused no adverse effects differing from those observed with the 1 mg/day dose.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Gonadotropin-releasing hormone receptor
Name Gonadotropin-releasing hormone receptor
Gene Name GNRHR
Pharmacological action yes
Actions agonist
References
  • Castellon E, Clementi M, Hitschfeld C, Sanchez C, Benitez D, Saenz L, Contreras H, Huidobro C: Effect of leuprolide and cetrorelix on cell growth, apoptosis, and GnRH receptor expression in primary cell cultures from human prostate carcinoma. Cancer Invest. 2006 Apr-May;24(3):261-8. - Pubmed
  • Borroni R, Di Blasio AM, Gaffuri B, Santorsola R, Busacca M, Vigano P, Vignali M: Expression of GnRH receptor gene in human ectopic endometrial cells and inhibition of their proliferation by leuprolide acetate. Mol Cell Endocrinol. 2000 Jan 25;159(1-2):37-43. - Pubmed
  • Imai A, Takagi A, Horibe S, Takagi H, Tamaya T: Fas and Fas ligand system may mediate antiproliferative activity of gonadotropin-releasing hormone receptor in endometrial cancer cells. Int J Oncol. 1998 Jul;13(1):97-100. - Pubmed
  • Murase M, Uemura T, Gao M, Inada M, Funabashi T, Hirahara F: GnRH antagonist-induced down-regulation of the mRNA expression of pituitary receptors: comparisons with GnRH agonist effects. Endocr J. 2005 Feb;52(1):131-7. - Pubmed
  • Khurana KK, Singh SB, Tatum AH, Schulz V, Badawy SZ: Maintenance of increased Bcl-2 expression in uterine leiomyomas after GnRH agonist therapy. J Reprod Med. 1999 Jun;44(6):487-92. - Pubmed
DTHybrid score 1.3256

Predictions


Id Partner name Gene Name Score
148 Lutropin-choriogonadotropic hormone receptor LHCGR 0.2629
3811 Cytochrome P450 19A1 CYP19A1 0.0487
1649 Small inducible cytokine A2 CCL2 0.0242
756 Sex hormone-binding globulin SHBG 0.017
614 Progesterone receptor PGR 0.0157
146 Androgen receptor AR 0.0135
136 Estrogen receptor ESR1 0.0125
4512 Cytochrome P450 3A4 CYP3A4 0.0079
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