DT-Web

DB00304 - Desogestrel


Identification
Name Desogestrel
Accession Number DB00304 (APRD00762)
Type small molecule
Description A synthetic progestational hormone used often as the progestogenic component of combined oral contraceptive agents. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 310.473
Groups approved
Monoisotopic Weight 310.229665582
Pharmacology
Indication For the prevention of pregnancy in women who elect to use this product as a method of contraception.
Mechanism of action Binds to the progesterone and estrogen receptors. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins like desogestrel will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge.
Absorption Following oral administration, the relative bioavailability of desogestrel, as measured by serum levels of etonogestrel, is approximately 84%. The absolute oral bioavailability is about 76%.
Protein binding 98.3%
Biotransformation Desogestrel is rapidly and completely metabolized by hydroxylation in the intestinal mucosa and on first pass through the liver. It is primarily metabolized to 3α-hydroxydesogestrel with small amounts of 3β-hydroxydesogestrel being formed. Both of these metabolites are then rapidly oxidized to its active metabolite, etonogestrel (3-ketodesogestrel). Other metabolites (e.g. 2-hydroxydesogestrel) with no pharmacologic action have also been identified. Desogestrel and some of its metabolites (e.g. 3β-hydroxydesogestrel, 15β-hydroxydesogestrel) may also undergo glucuronide and sulfate conjugation. Early in vitro studies demonstrated that CYP2C9 and possibly CYP2C19 were involved in the conversion of desogestrel to 3α-hydroxydesogestrel and 3β-hydroxydesogestrel (PMID 9864282); however, later clinical studies conducted in humans refuted this result (PMID 15963096). The latter study indicates that CYP3A4 plays an important role in metabolizing etonogestrel. Thus, strong CYP3A4 inhibitors or inducers could result in increased side effects or therapeutic failure, respectively.
Route of elimination Not Available
Toxicity Symptoms of overdose include nausea and vaginal bleeding.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Artemether Artemether may decrease the effectiveness of desogestrel by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.
Bexarotene Bexarotene may decrease the serum concentration of Contraceptives (Progestins). Since bexarotene is teratogenic and can lower serum concentrations of desogestrel, it is advised that women of childbearing potential use two forms of contraception (including at least one non-hormonal form).
Colesevelam Bile Acid Sequestrants may decrease the serum concentration of Contraceptives (Progestins). Administer oral progestin-containing contraceptives at least 1-4 hours prior to or 4-6 hours after administration of a bile acid sequestrant. Consider alternatives in order to avoid this combination when possible, due to the risk for impaired contraceptive effectiveness.
Lamotrigine The oral contraceptive decreases the effect of lamotrigine
Thiopental Thiopental may decrease the effect of Desogestrel. Contraceptive failure may occur. Alternative nonhomomonal contraception should be used during concomitant therapy.
Tretinoin Oral Tretinoin may decrease the effect of oral contraceptive, Desogestrel. An alternate form of contraception should be used during concomitant therapy.
Warfarin Desogestrol may alter the anticoagulant effect of warfarin. Concomitant therapy should be avoided. Monitor for changes in coagulation status if desogestrol is initiated, discontinued or dose changed.
Food Interactions Not Available

Targets


Progesterone receptor
Name Progesterone receptor
Gene Name PGR
Pharmacological action yes
Actions agonist
References
  • Bergink EW, van Meel F, Turpijn EW, van der Vies J: Binding of progestagens to receptor proteins in MCF-7 cells. J Steroid Biochem. 1983 Nov;19(5):1563-70. - Pubmed
  • Fuhrmann U, Slater EP, Fritzemeier KH: Characterization of the novel progestin gestodene by receptor binding studies and transactivation assays. Contraception. 1995 Jan;51(1):45-52. - Pubmed
  • Kloosterboer HJ, Vonk-Noordegraaf CA, Turpijn EW: Selectivity in progesterone and androgen receptor binding of progestagens used in oral contraceptives. Contraception. 1988 Sep;38(3):325-32. - Pubmed
  • Macpherson AM, Archer DF, Leslie S, Charnock-Jones DS, Makkink WK, Smith SK: The effect of etonogestrel on VEGF, oestrogen and progesterone receptor immunoreactivity and endothelial cell number in human endometrium. Hum Reprod. 1999 Dec;14(12):3080-7. - Pubmed
  • Charnock-Jones DS, Macpherson AM, Archer DF, Leslie S, Makkink WK, Sharkey AM, Smith SK: The effect of progestins on vascular endothelial growth factor, oestrogen receptor and progesterone receptor immunoreactivity and endothelial cell density in human endometrium. Hum Reprod. 2000 Aug;15 Suppl 3:85-95. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.6315
Estrogen receptor
Name Estrogen receptor
Gene Name ESR1
Pharmacological action yes
Actions agonist
References
  • Fuhrmann U, Slater EP, Fritzemeier KH: Characterization of the novel progestin gestodene by receptor binding studies and transactivation assays. Contraception. 1995 Jan;51(1):45-52. - Pubmed
  • Rabe T, Bohlmann MK, Rehberger-Schneider S, Prifti S: Induction of estrogen receptor-alpha and -beta activities by synthetic progestins. Gynecol Endocrinol. 2000 Apr;14(2):118-26. - Pubmed
  • Juchem M, Pollow K: Binding of oral contraceptive progestogens to serum proteins and cytoplasmic receptor. Am J Obstet Gynecol. 1990 Dec;163(6 Pt 2):2171-83. - Pubmed
DTHybrid score 0.8134

Predictions


Id Partner name Gene Name Score
6241 Nuclear receptor coactivator 2 NCOA2 0.2512
4512 Cytochrome P450 3A4 CYP3A4 0.0854
869 Estrogen receptor beta ESR2 0.0805
146 Androgen receptor AR 0.0601
2202 Steryl-sulfatase STS 0.0552
3811 Cytochrome P450 19A1 CYP19A1 0.0417
1588 Multidrug resistance protein 1 ABCB1 0.0405
871 Glucocorticoid receptor NR3C1 0.0401
756 Sex hormone-binding globulin SHBG 0.0335
66 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type II HSD3B2 0.0316
737 Mineralocorticoid receptor NR3C2 0.0306
4757 Cytochrome P450 2C9 CYP2C9 0.0254
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0247
596 3-oxo-5-alpha-steroid 4-dehydrogenase 1 SRD5A1 0.0229
6107 Cytochrome P450 3A7 CYP3A7 0.0192
4118 Cytochrome P450 3A5 CYP3A5 0.0191
4924 Cytochrome P450 2C8 CYP2C8 0.0189
1649 Small inducible cytokine A2 CCL2 0.0172
226 Gonadotropin-releasing hormone receptor GNRHR 0.0143
4200 Cytochrome P450 1A2 CYP1A2 0.0131
6228 Nuclear receptor coactivator 1 NCOA1 0.0122
687 Tyrosine-protein phosphatase non-receptor type 1 PTPN1 0.0118
6016 Cytochrome P450 2C19 CYP2C19 0.0116
862 Multidrug resistance-associated protein 1 ABCC1 0.0116
6024 Cytochrome P450 1A1 CYP1A1 0.0114
587 Serum albumin ALB 0.0102
3923 Cholinesterase BCHE 0.0094
381 Prolactin receptor PRLR 0.0093
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0092
290 Prostaglandin G/H synthase 2 PTGS2 0.0091
723 Cytosolic phospholipase A2 PLA2G4A 0.0091
232 Corticosteroid-binding globulin SERPINA6 0.0088
6141 Sodium/bile acid cotransporter SLC10A1 0.0086
57 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type I HSD3B1 0.0083
1898 Cytochrome P450 1B1 CYP1B1 0.0075
2107 Microtubule-associated protein 1A MAP1A 0.0075
6030 Cytochrome P450 2B6 CYP2B6 0.0074
5718 Cytochrome P450 2A6 CYP2A6 0.007
776 Bile salt export pump ABCB11 0.0069
4119 Cytochrome P450 2D6 CYP2D6 0.0069
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0062
6145 Solute carrier family 22 member 1 SLC22A1 0.0058
1852 Microtubule-associated protein 2 MAP2 0.0056
380 Cytochrome P450 17A1 CYP17A1 0.005
6013 Cytochrome P450 2E1 CYP2E1 0.0047
1284 Nuclear receptor subfamily 1 group I member 2 NR1I2 0.0045
6147 Solute carrier family 22 member 3 SLC22A3 0.0042
373 Transthyretin TTR 0.004
4210 Toll-like receptor 4 TLR4 0.0036
6144 Solute carrier family 22 member 2 SLC22A2 0.0036
6020 Aldehyde oxidase AOX1 0.0035
992 Protein tyrosine kinase 2 beta PTK2B 0.0033
1291 cAMP response element-binding protein CREB1 0.0033
3810 Catechol O-methyltransferase COMT 0.0031
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0031
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.0027
3809 Estrogen-related receptor gamma ESRRG 0.0027
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0026
3830 Calreticulin CALR 0.0025
6035 Nuclear receptor ROR-beta RORB 0.0024
6034 Hydroxyindole O-methyltransferase ASMT 0.0024
6036 Eosinophil peroxidase EPX 0.0024
6142 Solute carrier family 22 member 8 SLC22A8 0.0023
571 Melatonin receptor type 1A MTNR1A 0.0021
362 Melatonin receptor type 1B MTNR1B 0.0021
765 Indoleamine 2,3-dioxygenase IDO1 0.002
817 DNA topoisomerase 2-alpha TOP2A 0.002
6153 Solute carrier organic anion transporter family member 4A1 SLCO4A1 0.002
696 Kappa-type opioid receptor OPRK1 0.002
467 Delta-type opioid receptor OPRD1 0.002
847 Mu-type opioid receptor OPRM1 0.0019
6158 Solute carrier organic anion transporter family member 1C1 SLCO1C1 0.0018
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.0017
243 Ribosyldihydronicotinamide dehydrogenase [quinone] NQO2 0.0016
468 Cytochrome P450 4A11 CYP4A11 0.0016
1024 Solute carrier family 22 member 11 SLC22A11 0.0015
1192 Sulfotransferase 1A1 SULT1A1 0.0015
6149 Solute carrier family 22 member 10 SLC22A10 0.0014
6167 Organic solute transporter subunit beta OSTB 0.0014
6166 Organic solute transporter subunit alpha OSTA 0.0014
465 Calmodulin CALM1 0.0013
1757 Myeloperoxidase MPO 0.0013
6104 Dimethylaniline monooxygenase [N-oxide-forming] 1 FMO1 0.0013
6155 ATP-binding cassette transporter sub-family C member 11 ABCC11 0.0012
6085 Fatty acid-binding protein, intestinal FABP2 0.0011
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0011
6160 Solute carrier organic anion transporter family member 3A1 SLCO3A1 0.0011
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0011
4604 Liver carboxylesterase 1 CES1 0.001
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0009
6148 Multidrug resistance-associated protein 7 ABCC10 0.0008
2164 Multidrug resistance-associated protein 4 ABCC4 0.0008
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0007
1729 Solute carrier family 22 member 6 SLC22A6 0.0007
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