DT-Web

DB00269 - Chlorotrianisene


Identification
Name Chlorotrianisene
Accession Number DB00269 (APRD00715)
Type small molecule
Description A powerful synthetic, non-steroidal estrogen. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 380.864
Groups approved
Monoisotopic Weight 380.117922245
Pharmacology
Indication Used to treat symptoms of menopause, deficiencies in ovary function (including underdevelopment of female sexual characteristics and some types of infertility), and in rare cases, prostate cancer. Chlorotrianisene may also be used to prevent breast engorgement following childbirth.
Mechanism of action Chlorotrianisene binds to the estrogen receptor on various estrogen receptor bearing cells. Target cells include cells in the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary.
Absorption Absorption following oral administration is rapid.
Protein binding 50-80%
Biotransformation Metabolized principally in the liver, although the kidneys, gonads, and muscle tissues may be involved to some extent. The metabolic fate of the synthetic estrogens has not been fully elucidated.
Route of elimination Not Available
Toxicity Acute overdosage of large doses of oral contraceptives in chidren reportedly produces almost no toxicity except nausea and vomiting. Acute overdosage of estrogens may cause nausea, and withdrawal bleeding may occur in females.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Fosphenytoin The enzyme inducer, fosphenytoin, decreases the effect of the hormone agent, chlorotrianisene.
Griseofulvin The enzyme inducer, griseofulvin, decreases the effect of the hormone agent, chlorotrianisene.
Phenobarbital The enzyme inducer, phenobarbital, decreases the effect of the hormone agent, chlorotrianisene.
Phenytoin The enzyme inducer, phenytoin, decreases the effect of the hormone agent, chlorotrianisene.
Prednisolone The estrogenic agent, chlorotrianisene, may increase the effect of the corticosteroid, prednisolone.
Prednisone The estrogenic agent, chlorotrianisene, may increase the effect of corticosteroid, prednisone.
Primidone The enzyme inducer, primidone, decreases the effect of the hormone agent, chlorotrianisene.
Raloxifene Association not recommended
Food Interactions Not Available

Targets


Estrogen receptor
Name Estrogen receptor
Gene Name ESR1
Pharmacological action yes
Actions agonist
References
  • Kupfer D, Bulger WH: Inactivation of the uterine estrogen receptor binding of estradiol during P-450 catalyzed metabolism of chlorotrianisene (TACE). Speculation that TACE antiestrogenic activity involves covalent binding to the estrogen receptor. FEBS Lett. 1990 Feb 12;261(1):59-62. - Pubmed
  • Jordan VC, Gosden B: Inhibition of the uterotropic activity of estrogens and antiestrogens by the short acting antiestrogen LY117018. Endocrinology. 1983 Aug;113(2):463-8. - Pubmed
  • Wang JY, Xu BH, Tian LJ, Wang Y: [Clinical characteristics and potential prognostic factors of breast cancer patients with liver metastases] Zhonghua Zhong Liu Za Zhi. 2006 Aug;28(8):612-6. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.7155

Enzymes


Cytochrome P450 19A1
Name Cytochrome P450 19A1
Gene Name CYP19A1
Actions inducer
References
  • Adashi EY, Hsueh AJ: Estrogens augment the stimulation of ovarian aromatase activity by follicle-stimulating hormone in cultured rat granulosa cells. J Biol Chem. 1982 Jun 10;257(11):6077-83. - Pubmed
DTHybrid score 0.3401

Predictions


Id Partner name Gene Name Score
6241 Nuclear receptor coactivator 2 NCOA2 0.2306
4512 Cytochrome P450 3A4 CYP3A4 0.0979
869 Estrogen receptor beta ESR2 0.0884
146 Androgen receptor AR 0.0734
614 Progesterone receptor PGR 0.0726
756 Sex hormone-binding globulin SHBG 0.0414
1588 Multidrug resistance protein 1 ABCB1 0.0375
4200 Cytochrome P450 1A2 CYP1A2 0.0364
4757 Cytochrome P450 2C9 CYP2C9 0.0357
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.0267
4924 Cytochrome P450 2C8 CYP2C8 0.0261
6013 Cytochrome P450 2E1 CYP2E1 0.0239
6016 Cytochrome P450 2C19 CYP2C19 0.0238
6030 Cytochrome P450 2B6 CYP2B6 0.0236
226 Gonadotropin-releasing hormone receptor GNRHR 0.0233
5718 Cytochrome P450 2A6 CYP2A6 0.0216
260 Cytochrome P450 51 ERG11 0.0214
761 Cytochrome P450 51 ERG11 0.0214
3163 Cytochrome P450 51 cyp51 0.0214
563 Thyroid peroxidase TPO 0.0207
4116 Dihydropteroate synthetase Not Available 0.0199
148 Lutropin-choriogonadotropic hormone receptor LHCGR 0.0175
6024 Cytochrome P450 1A1 CYP1A1 0.0169
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0153
66 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type II HSD3B2 0.0149
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.014
596 3-oxo-5-alpha-steroid 4-dehydrogenase 1 SRD5A1 0.0135
6228 Nuclear receptor coactivator 1 NCOA1 0.0122
871 Glucocorticoid receptor NR3C1 0.0121
6107 Cytochrome P450 3A7 CYP3A7 0.012
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0119
687 Tyrosine-protein phosphatase non-receptor type 1 PTPN1 0.0118
6044 Serum paraoxonase/lactonase 3 PON3 0.0118
1898 Cytochrome P450 1B1 CYP1B1 0.0113
4118 Cytochrome P450 3A5 CYP3A5 0.0112
1649 Small inducible cytokine A2 CCL2 0.0108
4119 Cytochrome P450 2D6 CYP2D6 0.0094
381 Prolactin receptor PRLR 0.0093
776 Bile salt export pump ABCB11 0.0092
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0088
587 Serum albumin ALB 0.0087
6142 Solute carrier family 22 member 8 SLC22A8 0.0085
380 Cytochrome P450 17A1 CYP17A1 0.0084
57 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type I HSD3B1 0.0083
6020 Aldehyde oxidase AOX1 0.0082
3941 Amine oxidase [flavin-containing] A MAOA 0.0081
3957 Adenosine deaminase ADA 0.0079
1852 Microtubule-associated protein 2 MAP2 0.0078
1680 Solute carrier family 2, facilitated glucose transporter member 1 SLC2A1 0.0078
847 Mu-type opioid receptor OPRM1 0.0075
3809 Estrogen-related receptor gamma ESRRG 0.0075
2107 Microtubule-associated protein 1A MAP1A 0.0075
3923 Cholinesterase BCHE 0.0072
3939 Amine oxidase [flavin-containing] B MAOB 0.007
6141 Sodium/bile acid cotransporter SLC10A1 0.0068
1656 CYP2B protein CYP2B 0.0068
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.0065
1284 Nuclear receptor subfamily 1 group I member 2 NR1I2 0.0063
373 Transthyretin TTR 0.0061
6078 Neuronal acetylcholine receptor subunit beta-4 CHRNB4 0.006
3830 Calreticulin CALR 0.0059
217 Estradiol 17-beta-dehydrogenase 1 HSD17B1 0.0057
3810 Catechol O-methyltransferase COMT 0.0057
6145 Solute carrier family 22 member 1 SLC22A1 0.0056
6035 Nuclear receptor ROR-beta RORB 0.0055
6034 Hydroxyindole O-methyltransferase ASMT 0.0055
6036 Eosinophil peroxidase EPX 0.0055
6079 Neuronal acetylcholine receptor subunit alpha-3 CHRNA3 0.0054
3947 Xanthine dehydrogenase/oxidase XDH 0.005
144 Hemoglobin subunit alpha HBA1 0.0049
765 Indoleamine 2,3-dioxygenase IDO1 0.0048
564 Cellular retinoic acid-binding protein 1 CRABP1 0.0047
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0047
629 Alpha-2B adrenergic receptor ADRA2B 0.0047
862 Multidrug resistance-associated protein 1 ABCC1 0.0047
5934 Cytochrome P450 26A1 CYP26A1 0.0047
571 Melatonin receptor type 1A MTNR1A 0.0047
362 Melatonin receptor type 1B MTNR1B 0.0047
1010 Cytochrome P450 51A1 CYP51A1 0.0046
1178 Adenosine A2a receptor ADORA2A 0.0045
780 Retinoic acid receptor RXR-gamma RXRG 0.0043
229 Retinoic acid receptor beta RARB 0.0043
634 Squalene monooxygenase SQLE 0.0043
7196 Squalene monooxygenase ERG1 0.0043
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0042
730 Retinoic acid receptor alpha RARA 0.0042
290 Prostaglandin G/H synthase 2 PTGS2 0.0041
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.004
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.004
462 Intermediate conductance calcium-activated potassium channel protein 4 KCNN4 0.004
459 Retinoic acid receptor RXR-alpha RXRA 0.004
88 Retinoic acid receptor RXR-beta RXRB 0.0039
162 Retinoic acid receptor gamma-1 RARG 0.0039
567 Receptor tyrosine-protein kinase erbB-2 ERBB2 0.0038
467 Delta-type opioid receptor OPRD1 0.0038
2782 Complement C1s subcomponent C1S 0.0037
4210 Toll-like receptor 4 TLR4 0.0036
243 Ribosyldihydronicotinamide dehydrogenase [quinone] NQO2 0.0036
6153 Solute carrier organic anion transporter family member 4A1 SLCO4A1 0.0035
3815 Complement C1q subcomponent subunit A C1QA 0.0034
3816 Complement C1q subcomponent subunit B C1QB 0.0034
3817 Complement C1q subcomponent subunit C C1QC 0.0034
3818 Low affinity immunoglobulin gamma Fc region receptor III-A FCGR3A 0.0034
3819 Low affinity immunoglobulin gamma Fc region receptor II-a FCGR2A 0.0034
1102 Low affinity immunoglobulin gamma Fc region receptor III-B FCGR3B 0.0034
3821 Low affinity immunoglobulin gamma Fc region receptor II-c FCGR2C 0.0034
3814 Complement C1r subcomponent C1R 0.0034
3820 Low affinity immunoglobulin gamma Fc region receptor II-b FCGR2B 0.0034
992 Protein tyrosine kinase 2 beta PTK2B 0.0033
474 Acetylcholinesterase ACHE 0.0033
1291 cAMP response element-binding protein CREB1 0.0033
1192 Sulfotransferase 1A1 SULT1A1 0.0032
784 High affinity immunoglobulin gamma Fc receptor I FCGR1A 0.0032
6158 Solute carrier organic anion transporter family member 1C1 SLCO1C1 0.0032
6167 Organic solute transporter subunit beta OSTB 0.0032
6166 Organic solute transporter subunit alpha OSTA 0.0032
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.0031
1757 Myeloperoxidase MPO 0.0031
465 Calmodulin CALM1 0.0031
6104 Dimethylaniline monooxygenase [N-oxide-forming] 1 FMO1 0.003
468 Cytochrome P450 4A11 CYP4A11 0.003
844 Epidermal growth factor receptor EGFR 0.0028
6147 Solute carrier family 22 member 3 SLC22A3 0.0028
6031 Cytochrome P450 3A43 CYP3A43 0.0027
1024 Solute carrier family 22 member 11 SLC22A11 0.0026
6160 Solute carrier organic anion transporter family member 3A1 SLCO3A1 0.0026
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0025
6144 Solute carrier family 22 member 2 SLC22A2 0.0025
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0025
5923 Microtubule-associated protein tau MAPT 0.0024
5924 Microtubule-associated protein 4 MAP4 0.0024
6148 Multidrug resistance-associated protein 7 ABCC10 0.0024
458 Neuronal acetylcholine receptor subunit alpha-10 CHRNA10 0.0023
267 Plasminogen activator inhibitor 1 SERPINE1 0.0023
20 Prostaglandin G/H synthase 1 PTGS1 0.0023
4604 Liver carboxylesterase 1 CES1 0.0022
7 Nitric oxide synthase, inducible NOS2 0.0022
6931 Calcium-activated potassium channel subunit beta-1 KCNMB1 0.0022
6933 Calcium-activated potassium channel subunit beta-4 KCNMB4 0.0022
6932 Calcium-activated potassium channel subunit beta-3 KCNMB3 0.0022
6934 Small conductance calcium-activated potassium channel protein 1 KCNN1 0.0022
6935 Small conductance calcium-activated potassium channel protein 2 KCNN2 0.0022
6936 Small conductance calcium-activated potassium channel protein 3 KCNN3 0.0022
6143 Solute carrier family 22 member 7 SLC22A7 0.0022
273 Apoptosis regulator Bcl-2 BCL2 0.0021
6221 Steroid hormone receptor ERR1 ESRRA 0.0021
817 DNA topoisomerase 2-alpha TOP2A 0.002
6002 Prostaglandin E2 receptor EP4 subtype PTGER4 0.002
696 Kappa-type opioid receptor OPRK1 0.002
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.002
5463 Calcium-activated potassium channel subunit beta 2 KCNMB2 0.0019
29 Tubulin beta-1 chain TUBB1 0.0019
2164 Multidrug resistance-associated protein 4 ABCC4 0.0019
84 Nuclear receptor 0B1 NR0B1 0.0019
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0019
4131 Prostaglandin E2 receptor, EP3 subtype PTGER3 0.0018
1457 Long-chain-fatty-acid--CoA ligase 4 ACSL4 0.0018
406 Prostaglandin E2 receptor, EP2 subtype PTGER2 0.0018
6106 Cytochrome P450 2C18 CYP2C18 0.0018
469 Annexin A1 ANXA1 0.0018
6014 Cytochrome P450 2A13 CYP2A13 0.0017
6181 UDP-glucuronosyltransferase 1-8 UGT1A8 0.0016
6177 UDP-glucuronosyltransferase 1-10 UGT1A10 0.0016
73 Prostaglandin E2 receptor, EP1 subtype PTGER1 0.0016
1729 Solute carrier family 22 member 6 SLC22A6 0.0016
514 Potassium voltage-gated channel subfamily H member 6 KCNH6 0.0015
772 Potassium voltage-gated channel subfamily H member 7 KCNH7 0.0015
2222 Equilibrative nucleoside transporter 1 SLC29A1 0.0014
6152 Solute carrier organic anion transporter family member 2A1 SLCO2A1 0.0014
6149 Solute carrier family 22 member 10 SLC22A10 0.0014
610 Calcium-activated potassium channel subunit alpha 1 KCNMA1 0.0014
6136 Multidrug resistance-associated protein 5 ABCC5 0.0013
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0013
737 Mineralocorticoid receptor NR3C2 0.0012
6155 ATP-binding cassette transporter sub-family C member 11 ABCC11 0.0012
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0012
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0012
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0012
238 Peroxisome proliferator-activated receptor gamma PPARG 0.0012
6085 Fatty acid-binding protein, intestinal FABP2 0.0011
833 Organic cation/carnitine transporter 1 SLC22A4 0.0011
291 Nitric-oxide synthase, endothelial NOS3 0.0011
↑