DT-Web

DB00648 - Mitotane


Identification
Name Mitotane
Accession Number DB00648 (APRD00494)
Type small molecule
Description A derivative of the insecticide dichlorodiphenyldichloroethane that specifically inhibits cells of the adrenal cortex and their production of hormones. It is used to treat adrenocortical tumors and causes CNS damage, but no bone marrow depression. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 320.041
Groups approved
Monoisotopic Weight 317.953661148
Pharmacology
Indication For treatment of inoperable adrenocortical tumours; Cushing's syndrome
Mechanism of action Its biochemical mechanism of action is unknown, although data are available to suggest that the drug modifies the peripheral metabolism of steroids as well as directly suppressing the adrenal cortex.
Absorption About 40% oral Lysodren is absorbed
Protein binding 6%
Biotransformation Hepatic and renal
Route of elimination A variable amount of metabolite (1%-17%) is excreted in the bile and the balance is apparently stored in the tissues.
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Acenocoumarol Mitotane may decrease the anticoagulant effect of acenocoumarol.
Anisindione Mitotane may decrease the anticoagulant effect of anisindione.
Dicumarol Mitotane may decrease the anticoagulant effect of dicumarol.
Spironolactone Spironolactone antagonizes the effect of mitotane
Warfarin Mitotane may decrease the anticoagulant effect of warfarin.
Food Interactions
  • Take without regard to meals.

Targets


Cytochrome P450 11B1, mitochondrial
Name Cytochrome P450 11B1, mitochondrial
Gene Name CYP11B1
Pharmacological action yes
Actions inducer
References
  • Lindhe O, Skogseid B, Brandt I: Cytochrome P450-catalyzed binding of 3-methylsulfonyl-DDE and o,p'-DDD in human adrenal zona fasciculata/reticularis. J Clin Endocrinol Metab. 2002 Mar;87(3):1319-26. - Pubmed
DTHybrid score 0.3726
Adrenodoxin, mitochondrial
Name Adrenodoxin, mitochondrial
Gene Name FDX1
Pharmacological action unknown
Actions unknown
References
  • Kandul SV, Iatsyk MI, Kononenko VIa: [Comparative study of the effect of chloditan on the concentration of cytochrome P-450 and adrenodoxin in various organs of the dog and rat] Fiziol Zh. 1986 Sep-Oct;32(5):579-84. - Pubmed
  • Cabrini DA, Campos MM, Tratsk KS, Merino VF, Silva JA Jr, Souza GE, Avellar MC, Pesquero JB, Calixto JB: Molecular and pharmacological evidence for modulation of kinin B(1) receptor expression by endogenous glucocorticoids hormones in rats. Br J Pharmacol. 2001 Jan;132(2):567-77. - Pubmed
  • Cai W, Counsell RE, Schteingart DE, Sinsheimer JE, Vaz AD, Wotring LL: Adrenal proteins bound by a reactive intermediate of mitotane. Cancer Chemother Pharmacol. 1997;39(6):537-40. - Pubmed
DTHybrid score 0.5964

Carriers


Predictions


Id Partner name Gene Name Score
871 Glucocorticoid receptor NR3C1 0.4166
4512 Cytochrome P450 3A4 CYP3A4 0.1131
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.0911
146 Androgen receptor AR 0.0877
3811 Cytochrome P450 19A1 CYP19A1 0.0724
1588 Multidrug resistance protein 1 ABCB1 0.0592
869 Estrogen receptor beta ESR2 0.0553
4118 Cytochrome P450 3A5 CYP3A5 0.0518
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.051
6107 Cytochrome P450 3A7 CYP3A7 0.0441
380 Cytochrome P450 17A1 CYP17A1 0.0408
136 Estrogen receptor ESR1 0.0349
381 Prolactin receptor PRLR 0.0347
723 Cytosolic phospholipase A2 PLA2G4A 0.0338
737 Mineralocorticoid receptor NR3C2 0.0338
614 Progesterone receptor PGR 0.0326
4924 Cytochrome P450 2C8 CYP2C8 0.0283
587 Serum albumin ALB 0.0277
6016 Cytochrome P450 2C19 CYP2C19 0.0266
4757 Cytochrome P450 2C9 CYP2C9 0.0252
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.0237
5718 Cytochrome P450 2A6 CYP2A6 0.0236
260 Cytochrome P450 51 ERG11 0.0225
761 Cytochrome P450 51 ERG11 0.0225
3163 Cytochrome P450 51 cyp51 0.0225
4119 Cytochrome P450 2D6 CYP2D6 0.0225
469 Annexin A1 ANXA1 0.0202
6030 Cytochrome P450 2B6 CYP2B6 0.0196
4200 Cytochrome P450 1A2 CYP1A2 0.0179
1680 Solute carrier family 2, facilitated glucose transporter member 1 SLC2A1 0.0177
1649 Small inducible cytokine A2 CCL2 0.0167
217 Estradiol 17-beta-dehydrogenase 1 HSD17B1 0.0163
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0146
6145 Solute carrier family 22 member 1 SLC22A1 0.0142
6142 Solute carrier family 22 member 8 SLC22A8 0.014
6013 Cytochrome P450 2E1 CYP2E1 0.014
94 5-hydroxytryptamine 4 receptor HTR4 0.0138
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0138
226 Gonadotropin-releasing hormone receptor GNRHR 0.0136
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0134
4604 Liver carboxylesterase 1 CES1 0.0116
2298 Cytochrome P450-cam camC 0.0113
629 Alpha-2B adrenergic receptor ADRA2B 0.011
118 Organic cation/carnitine transporter 2 SLC22A5 0.0108
462 Intermediate conductance calcium-activated potassium channel protein 4 KCNN4 0.0095
6024 Cytochrome P450 1A1 CYP1A1 0.0095
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0094
3923 Cholinesterase BCHE 0.0093
290 Prostaglandin G/H synthase 2 PTGS2 0.009
1898 Cytochrome P450 1B1 CYP1B1 0.0085
831 D(2) dopamine receptor DRD2 0.0081
103 Muscarinic acetylcholine receptor M1 CHRM1 0.008
6147 Solute carrier family 22 member 3 SLC22A3 0.0079
6158 Solute carrier organic anion transporter family member 1C1 SLCO1C1 0.0079
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0059
776 Bile salt export pump ABCB11 0.0058
833 Organic cation/carnitine transporter 1 SLC22A4 0.0055
6931 Calcium-activated potassium channel subunit beta-1 KCNMB1 0.0054
6933 Calcium-activated potassium channel subunit beta-4 KCNMB4 0.0054
6932 Calcium-activated potassium channel subunit beta-3 KCNMB3 0.0054
6936 Small conductance calcium-activated potassium channel protein 3 KCNN3 0.0054
6934 Small conductance calcium-activated potassium channel protein 1 KCNN1 0.0054
6935 Small conductance calcium-activated potassium channel protein 2 KCNN2 0.0054
6143 Solute carrier family 22 member 7 SLC22A7 0.0051
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.005
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.005
1010 Cytochrome P450 51A1 CYP51A1 0.005
5934 Cytochrome P450 26A1 CYP26A1 0.005
1024 Solute carrier family 22 member 11 SLC22A11 0.0048
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0046
15 Voltage-dependent T-type calcium channel subunit alpha-1I CACNA1I 0.0046
6106 Cytochrome P450 2C18 CYP2C18 0.0046
6014 Cytochrome P450 2A13 CYP2A13 0.0046
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 0.0046
5463 Calcium-activated potassium channel subunit beta 2 KCNMB2 0.0045
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0045
6144 Solute carrier family 22 member 2 SLC22A2 0.0044
535 Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G 0.0044
964 Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H 0.0042
6104 Dimethylaniline monooxygenase [N-oxide-forming] 1 FMO1 0.004
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0039
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0039
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0039
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0038
514 Potassium voltage-gated channel subfamily H member 6 KCNH6 0.0037
772 Potassium voltage-gated channel subfamily H member 7 KCNH7 0.0037
6154 Multidrug and toxin extrusion protein 1 SLC47A1 0.0036
6085 Fatty acid-binding protein, intestinal FABP2 0.0036
6141 Sodium/bile acid cotransporter SLC10A1 0.0035
6031 Cytochrome P450 3A43 CYP3A43 0.0035
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0034
610 Calcium-activated potassium channel subunit alpha 1 KCNMA1 0.0032
124 Histamine H2 receptor HRH2 0.0032
1284 Nuclear receptor subfamily 1 group I member 2 NR1I2 0.0032
6153 Solute carrier organic anion transporter family member 4A1 SLCO4A1 0.0031
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0028
3941 Amine oxidase [flavin-containing] A MAOA 0.0027
6148 Multidrug resistance-associated protein 7 ABCC10 0.0027
7 Nitric oxide synthase, inducible NOS2 0.0025
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.0025
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0025
291 Nitric-oxide synthase, endothelial NOS3 0.0024
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0024
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0021
1729 Solute carrier family 22 member 6 SLC22A6 0.002
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