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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:08:13
Primary Accession Number DB00648
Secondary Accession Number
  • APRD00494
Name Mitotane
Drug Type
  • Approved
  • 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]
Synonyms Not Available
Brand Names
  1. Chloditan
  2. Chlodithan
  3. Chlodithane
  4. Khlodithan
  5. Lysodren
  6. Mitotan
  7. Mitotanum [INN-Latin]
Brand Mixtures Not Available
Chemical IUPAC Name 1-chloro-4-[2,2-dichloro-1-(2-chlorophenyl)ethyl]benzene
Chemical Formula C14H10Cl4
Chemical Structure Structure
CAS Registry Number 53-19-0
InChI Identifier InChI=1/C14H10Cl4/c15-10-7-5-9(6-8-10)13(14(17)18)11-3-1-2-4-12(11)16/h1-8,13-14H
InChI Key JWBOIMRXGHLCPP-UHFFFAOYAD
KEGG Drug D00420 Link Image
KEGG Compound Not Available
PubChem Compound 4211 Link Image
PubChem Substance 148675 Link Image
ChEBI ID Not Available
PharmGKB ID PA450525 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 00463221 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/mitotane.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Mitotane Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 320.0410
Monoisotopic Molecular Weight 317.9537
State Solid
Melting Point 77 oC
Experimental Water Solubility 0.1 mg/L Source: PhysProp
Predicted Water Solubility 9.42e-06 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 6 Source: PhysProp
Predicted LogP 6.08 Calculated using ALOGPS
Experimental LogS -6.51 [ADME Research, USCD]
Predicted LogS -7.53 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES ClC(Cl)[C@@H](C1=CC=C(Cl)C=C1)C1=CC=CC=C1Cl
Canonical SMILES ClC(Cl)C(C1=CC=C(Cl)C=C1)C1=CC=CC=C1Cl
Drug Category
  • Antineoplastic Agents
  • Antineoplastic Agents, Hormonal
ATC Codes
AHFS Codes
  • 10:00.00
Indication For treatment of inoperable adrenocortical tumours; Cushing's syndrome
Pharmacology Mitotane is an oral chemotherapeutic agent indicated in the treatment of inoperable adrenal cortical carcinoma of both functional and nonfunctional types. Mitotane can best be described as an adrenal cytotoxic agent, although it can cause adrenal inhibition, apparently without cellular destruction. The administration of Mitotane alters the extra-adrenal metabolism of cortisol in man; leading to a reduction in measurable 17-hydroxy corticosteroids, even though plasma levels of corticosteroids do not fall. The drug apparently causes increased formation of 6-B-hydroxyl cortisol.
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
Toxicity Not Available
Protein Binding 6%
Biotransformation Hepatic and renal
Half Life 18-159 days
Dosage Forms
Form Route
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acenocoumarol Mitotane decreases the anticoagulant effect
Anisindione Mitotane decreases the anticoagulant effect
Dicumarol Mitotane decreases the anticoagulant effect
Spironolactone Spironolactone antagonizes the effect of mitotane
Warfarin Mitotane decreases the anticoagulant effect
Food Interactions
  • Take without regard to meals.
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Corticosteroid-binding globulin
  2. Adrenodoxin, mitochondrial
  3. Sex hormone-binding globulin
  4. Cytochrome P450 11B1, mitochondrial
Drug Target 1 [top]
Target 1 ID 232
Target 1 Name Corticosteroid-binding globulin
Target 1 Synonyms
  1. CBG
  2. Corticosteroid-binding globulin precursor
  3. Serpin A6
  4. Transcortin
Target 1 Gene Name SERPINA6
Target 1 Protein Sequence >Corticosteroid-binding globulin precursor 
MPLLLYTCLLWLPTSGLWTVQAMDPNAAYVNMSNHHRGLASANVDFAFSLYKHLVALSPK
KNIFISPVSISMALAMLSLGTCGHTRAQLLQGLGFNLTERSETEIHQGFQHLHQLFAKSD
TSLEMTMGNALFLDGSLELLESFSADIKHYYESEVLAMNFQDWATASRQINSYVKNKTQG
KIVDLFSGLDSPAILVLVNYIFFKGTWTQPFDLASTREENFYVDETTVVKVPMMLQSSTI
SYLHDSELPCQLVQMNYVGNGTVFFILPDKGKMNTVIAALSRDTINRWSAGLTSSQVDLY
IPKVTISGVYDLGDVLEEMGIADLFTNQANFSRITQDAQLKSSKVVHKAVLQLNEEGVDT
AGSTGVTLNLTSKPIILRFNQPFIIMIFDHFTWSSLFLARVMNPV
Target 1 Number of Residues 411
Target 1 Molecular Weight 45141
Target 1 Theoretical pI 5.94
Target 1 GO Classification
Function
enzyme regulator activity
enzyme inhibitor activity
protease inhibitor activity
endopeptidase inhibitor activity
serine-type endopeptidase inhibitor activity
Process
Not Available
Component
Not Available
Target 1 General Function Involved in serine-type endopeptidase inhibitor activity
Target 1 Specific Function Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • 1-22
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 179971 Link Image
Target 1 UniProtKB/Swiss-Prot ID P08185 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name CBG_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Secreted protein
Target 1 Gene Sequence >1218 bp 
ATGCCACTCCTCCTGTACACCTGTCTTCTCTGGCTGCCCACCAGCGGCCTCTGGACCGTC
CAGGCCATGGATCCTAACGCTGCTTATGTGAACATGAGTAACCATCACCGGGGCCTGGCT
TCAGCCAACGTTGACTTTGCCTTCAGCCTGTATAAGCACCTAGTGGCCTTGAGTCCCAAA
AAGAACATTTTCATCTCCCCTGTGAGCATCTCCATGGCCTTAGCTATGCTGTCCCTGGGC
ACCTGTGGCCACACACGGGCCCAGCTTCTCCAGGGCCTGGGTTTCAACCTCACTGAGAGG
TCTGAGACTGAGATCCACCAGGGTTTCCAGCACCTGCACCAACTCTTTGCAAAGTCAGAC
ACCAGCTTAGAAATGACTATGGGCAATGCCTTGTTTCTTGATGGCAGCCTGGAGTTGCTG
GAGTCATTCTCAGCAGACATCAAGCACTACTATGAGTCAGAGGTCTTGGCTATGAATTTC
CAGGACTGGGCAACAGCCAGCAGACAGATCAACAGCTATGTCAAGAATAAGACACAGGGG
AAAATTGTCGACTTGTTTTCAGGGCTGGATAGCCCAGCCATCCTCGTCCTGGTCAACTAT
ATCTTCTTCAAAGGCACATGGACACAGCCCTTTGACCTGGCAAGCACCAGGGAGGAGAAC
TTCTATGTGGACGAGACAACTGTGGTGAAGGTGCCCATGATGTTGCAGTCGAGCACCATC
AGTTACCTTCATGACTCAGAGCTCCCCTGCCAGCTGGTGCAGATGAACTACGTGGGCAAT
GGGACTGTCTTCTTCATCCTTCCGGACAAGGGGAAGATGAACACAGTCATCGCTGCACTG
AGCCGGGACACGATTAACAGGTGGTCCGCAGGCCTGACCAGCAGCCAGGTGGACCTGTAC
ATTCCAAAGGTCACCATCTCTGGAGTCTATGACCTTGGAGATGTGCTGGAGGAAATGGGC
ATTGCAGACTTGTTCACCAACCAGGCAAATTTCTCACGCATCACCCAGGACGCCCAGCTG
AAGTCATCAAAGGTGGTCCATAAAGCTGTGCTGCAACTCAATGAGGAGGGTGTGGACACA
GCTGGCTCCACTGGGGTCACCCTAAACCTGACGTCCAAGCCTATCATCTTGCGTTTCAAC
CAGCCCTTCATCATCATGATCTTCGACCACTTCACCTGGAGCAGCCTTTTCCTGGCGAGG
GTTATGAACCCAGTGTAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID SERPINA6 Link Image
Target 1 GenAtlas ID SERPINA6 Link Image
Target 1 HGNC ID HGNC:1540 Link Image
Target 1 Chromosome Location 14
Target 1 Locus 14q32.1
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Emptoz-Bonneton A, Cousin P, Seguchi K, Avvakumov GV, Bully C, Hammond GL, Pugeat M: Novel human corticosteroid-binding globulin variant with low cortisol-binding affinity. J Clin Endocrinol Metab. 2000 Jan;85(1):361-7. [PubMed Link Image]
  2. Smith CL, Power SG, Hammond GL: A Leu----His substitution at residue 93 in human corticosteroid binding globulin results in reduced affinity for cortisol. J Steroid Biochem Mol Biol. 1992 Aug;42(7):671-6. [PubMed Link Image]
  3. Hammond GL, Smith CL, Goping IS, Underhill DA, Harley MJ, Reventos J, Musto NA, Gunsalus GL, Bardin CW: Primary structure of human corticosteroid binding globulin, deduced from hepatic and pulmonary cDNAs, exhibits homology with serine protease inhibitors. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5153-7. [PubMed Link Image]
  4. Kato EA, Hsu BR, Kuhn RW: Comparative structural analyses of corticosteroid binding globulin. J Steroid Biochem. 1988 Feb;29(2):213-20. [PubMed Link Image]
  5. Bardin CW, Gunsalus GL, Musto NA, Cheng CY, Reventos J, Smith C, Underhill DA, Hammond G: Corticosteroid binding globulin, testosterone-estradiol binding globulin, and androgen binding protein belong to protein families distinct from steroid receptors. J Steroid Biochem. 1988;30(1-6):131-9. [PubMed Link Image]
  6. Van Baelen H, Power SG, Hammond GL: Decreased cortisol-binding affinity of transcortin Leuven is associated with an amino acid substitution at residue-93. Steroids. 1993 Jun;58(6):275-7. [PubMed Link Image]
Target 1 Drug References
  1. Nader N, Raverot G, Emptoz-Bonneton A, Dechaud H, Bonnay M, Baudin E, Pugeat M: Mitotane has an estrogenic effect on sex hormone-binding globulin and corticosteroid-binding globulin in humans. J Clin Endocrinol Metab. 2006 Jun;91(6):2165-70. Epub 2006 Mar 21. [PubMed Link Image]
  2. Tron'ko MD: [Effect of chlodithane (o,p'-DDD) on transcortin binding ability in Itsenko-Cushing's disease] Fiziol Zh. 1970 Nov-Dec;16(6):844-5. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 269
Target 2 Name Adrenodoxin, mitochondrial
Target 2 Synonyms
  1. Adrenal ferredoxin
  2. Adrenodoxin, mitochondrial precursor
  3. Ferredoxin- 1
  4. Hepatoredoxin
Target 2 Gene Name FDX1
Target 2 Protein Sequence >Adrenodoxin, mitochondrial precursor 
MAAAGGARLLRAASAVLGGPAGRWLHHAGSRAGSSGLLRNRGPGGSAEASRSLSVSARAR
SSSEDKITVHFINRDGETLTTKGKVGDSLLDVVVENNLDIDGFGACEGTLACSTCHLIFE
DHIYEKLDAITDEENDMLDLAYGLTDRSRLGCQICLTKSMDNMTVRVPETVADARQSIDV
GKTS
Target 2 Number of Residues 187
Target 2 Molecular Weight 19393
Target 2 Theoretical pI 5.62
Target 2 GO Classification
Function
binding
ion binding
cation binding
transition metal ion binding
iron ion binding
transporter activity
electron transporter activity
Process
physiological process
metabolism
cellular metabolism
generation of precursor metabolites and energy
electron transport
Component
Not Available
Target 2 General Function Energy production and conversion
Target 2 Specific Function Participates in the synthesis of thyroid hormones. Transfers electrons from adrenodoxin reductase to the cholesterol side chain cleavage cytochrome P450
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 557734 Link Image
Target 2 UniProtKB/Swiss-Prot ID P10109 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name ADX_HUMAN Link Image
Target 2 PDB ID 1L6V Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Mitochondrion
  • mitochondrial matrix
Target 2 Gene Sequence >555 bp 
ATGGCTGCCGCTGGGGGCGCCCGGCTGCTGCGCGCCGCTTCTGCTGTCCTCGGCGGCCCG
GCCGGCCGGTGGCTGCACCACGCTGGGTCCCGCGCTGGATCCAGCGGCCTGCTGAGGAAC
CGGGGGCCGGGCGGTAGCGCGGAGGCGAGCCGGTCGCTGAGCGTGTCGGCGCGGGCCCGG
AGCAGCTCAGAAGATAAAATAACAGTCCACTTTATAAACCGTGATGGTGAAACATTAACA
ACCAAAGGAAAAGTTGGTGATTCTCTGCTAGATGTTGTGGTTGAAAATAATCTAGATATT
GATGGCTTTGGTGCATGTGAGGGAACCCTGGCTTGTTCAACCTGTCACCTCATCTTTGAA
GATCACATATATGAGAAGTTAGATGCAATCACTGATGAGGAGAATGACATGCTCGATCTG
GCATATGGACTAACAGACAGATCACGGTTGGGCTGCCAAATCTGTTTGACAAAATCTATG
GACAATATGACTGTTCGAGTGCCTGAAACAGTGGCTGATGCCAGACAATCCATTGATGTG
GGCAAGACCTCCTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID FDX1 Link Image
Target 2 GenAtlas ID FDX1 Link Image
Target 2 HGNC ID HGNC:3638 Link Image
Target 2 Chromosome Location 11
Target 2 Locus 11q22
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Johnson D, Norman S, Tuckey RC, Martin LL: Electrochemical behaviour of human adrenodoxin on a pyrolytic graphite electrode. Bioelectrochemistry. 2003 Apr;59(1-2):41-7. [PubMed Link Image]
  2. Skjeldal L, Markley JL, Coghlan VM, Vickery LE: 1H NMR spectra of vertebrate [2Fe-2S] ferredoxins. Hyperfine resonances suggest different electron delocalization patterns from plant ferredoxins. Biochemistry. 1991 Sep 17;30(37):9078-83. [PubMed Link Image]
  3. Chang CY, Wu DA, Mohandas TK, Chung BC: Structure, sequence, chromosomal location, and evolution of the human ferredoxin gene family. DNA Cell Biol. 1990 Apr;9(3):205-12. [PubMed Link Image]
  4. Mittal S, Zhu YZ, Vickery LE: Molecular cloning and sequence analysis of human placental ferredoxin. Arch Biochem Biophys. 1988 Aug 1;264(2):383-91. [PubMed Link Image]
  5. Chang CY, Wu DA, Lai CC, Miller WL, Chung BC: Cloning and structure of the human adrenodoxin gene. DNA. 1988 Nov;7(9):609-15. [PubMed Link Image]
  6. Picado-Leonard J, Voutilainen R, Kao LC, Chung BC, Strauss JF 3rd, Miller WL: Human adrenodoxin: cloning of three cDNAs and cycloheximide enhancement in JEG-3 cells. J Biol Chem. 1988 Mar 5;263(7):3240-4. [PubMed Link Image]
Target 2 Drug References
  1. 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 Link Image]
  2. 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 Link Image]
  3. 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 Link Image]
Drug Target 3 [top]
Target 3 ID 756
Target 3 Name Sex hormone-binding globulin
Target 3 Synonyms
  1. ABP
  2. SBP
  3. SHBG
  4. Sex hormone-binding globulin precursor
  5. Sex steroid-binding protein
  6. TeBG
  7. Testis-specific androgen-binding protein
  8. Testosterone-estradiol- binding globulin
  9. Testosterone-estrogen-binding globulin
Target 3 Gene Name SHBG
Target 3 Protein Sequence >Sex hormone-binding globulin precursor 
MESRGPLATSRLLLLLLLLLLRHTRQGWALRPVLPTQSAHDPPAVHLSNGPGQEPIAVMT
FDLTKITKTSSSFEVRTWDPEGVIFYGDTNPKDDWFMLGLRDGRPEIQLHNHWAQLTVGA
GPRLDDGRWHQVEVKMEGDSVLLEVDGEEVLRLRQVSGPLTSKRHPIMRIALGGLLFPAS
NLRLPLVPALDGCLRRDSWLDKQAEISASAPTSLRSCDVESNPGIFLPPGTQAEFNLRDI
PQPHAEPWAFSLDLGLKQAAGSGHLLALGTPENPSWLSLHLQDQKVVLSSGSGPGLDLPL
VLGLPLQLKLSMSRVVLSQGSKMKALALPPLGLAPLLNLWAKPQGRLFLGALPGEDSSTS
FCLNGLWAQGQRLDVDQALNRSHEIWTHSCPQSPGNGTDASH
Target 3 Number of Residues 408
Target 3 Molecular Weight 43780
Target 3 Theoretical pI 6.70
Target 3 GO Classification Not Available
Target 3 General Function Involved in androgen binding
Target 3 Specific Function Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • 1-29
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 296673 Link Image
Target 3 UniProtKB/Swiss-Prot ID P04278 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name SHBG_HUMAN Link Image
Target 3 PDB ID 1F5F Link Image
Target 3 PDB File Show
Target 3 3D Structure
Target 3 Cellular Location
  • Secreted protein. In testis, it is synthesized by the Sertoli cells, secreted into the lumen of the
Target 3 Gene Sequence >1209 bp 
ATGGAGAGCAGAGGCCCACTGGCTACCTCGCGCCTGCTGCTGTTGCTGCTGTTGCTACTA
CTGCGTCACACCCGCCAGGGATGGGCCCTGAGACCTGTTCTCCCCACCCAGAGTGCCCAC
GACCCTCCGGCTGTCCACCTCAGCAATGGCCCAGGACAAGAGCCTATCGCTGTCATGACC
TTTGACCTCACCAAGATCACAAAAACCTCCTCCTCCTTTGAGGTTCGAACCTGGGACCCA
GAGGGAGTGATTTTTTATGGGGATACCAACCCTAAGGATGACTGGTTTATGCTGGGACTT
CGAGACGGCAGGCCTGAGATCCAACTGCACAATCACTGGGCCCAGCTTACGGTGGGTGCT
GGACCACGGCTGGATGATGGGAGATGGCACCAGGTGGAAGTCAAGATGGAGGGGGACTCT
GTGCTGCTGGAGGTGGATGGGGAGGAGGTGCTGCGCCTGAGACAGGTCTCTGGGCCCCTG
ACCAGCAAACGCCATCCCATCATGAGGATTGCGCTTGGGGGGCTGCTCTTCCCCGCTTCC
AACCTTCGGTTGCCGCTGGTTCCTGCCCTGGATGGCTGCCTGCGCCGGGATTCCTGGCTG
GACAAACAGGCCGAGATCTCAGCATCTGCCCCCACTAGCCTCAGAAGCTGTGATGTAGAA
TCAAATCCCGGGATATTTCTCCCTCCAGGGACTCAGGCAGAATTCAATCTCCGAGACATT
CCCCAGCCTCATGCAGAGCCCTGGGCCTTCTCTTTGGACCTGGGACTCAAGCAGGCAGCA
GGCTCAGGCCACCTCCTTGCTCTTGGGACACCAGAGAACCCATCTTGGCTCAGTCTCCAC
CTCCAAGATCAAAAGGTGGTGTTGTCTTCTGGGTCGGGGCCAGGGCTGGATCTGCCCCTG
GTCTTGGGACTCCCTCTTCAGCTGAAGCTGAGTATGTCCAGGGTGGTCTTGAGCCAAGGG
TCGAAGATGAAGGCCCTTGCCCTGCCTCCCTTAGGCCTGGCTCCCCTCCTTAACCTCTGG
GCCAAGCCTCAAGGGCGTCTCTTCCTGGGGGCTTTACCAGGAGAAGACTCTTCCACCTCT
TTTTGCCTGAATGGCCTTTGGGCACAAGGTCAGAGGCTGGATGTGGACCAGGCCCTGAAC
AGAAGCCATGAGATCTGGACTCACAGCTGCCCCCAGAGCCCAGGCAATGGCACTGACGCT
TCCCATTAA
Target 3 GenBank Gene ID
Target 3 GeneCard ID SHBG Link Image
Target 3 GenAtlas ID SHBG Link Image
Target 3 HGNC ID HGNC:10839 Link Image
Target 3 Chromosome Location 17
Target 3 Locus 17p13-p12
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed Link Image]
  2. Grishkovskaya I, Avvakumov GV, Sklenar G, Dales D, Hammond GL, Muller YA: Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain. EMBO J. 2000 Feb 15;19(4):504-12. [PubMed Link Image]
  3. Grishkovskaya I, Avvakumov GV, Hammond GL, Catalano MG, Muller YA: Steroid ligands bind human sex hormone-binding globulin in specific orientations and produce distinct changes in protein conformation. J Biol Chem. 2002 Aug 30;277(35):32086-93. Epub 2002 Jun 13. [PubMed Link Image]
  4. Power SG, Bocchinfuso WP, Pallesen M, Warmels-Rodenhiser S, Van Baelen H, Hammond GL: Molecular analyses of a human sex hormone-binding globulin variant: evidence for an additional carbohydrate chain. J Clin Endocrinol Metab. 1992 Oct;75(4):1066-70. [PubMed Link Image]
  5. Gershagen S, Lundwall A, Fernlund P: Characterization of the human sex hormone binding globulin (SHBG) gene and demonstration of two transcripts in both liver and testis. Nucleic Acids Res. 1989 Nov 25;17(22):9245-58. [PubMed Link Image]
  6. Hammond GL, Underhill DA, Rykse HM, Smith CL: The human sex hormone-binding globulin gene contains exons for androgen-binding protein and two other testicular messenger RNAs. Mol Endocrinol. 1989 Nov;3(11):1869-76. [PubMed Link Image]
  7. Que BG, Petra PH: Characterization of a cDNA coding for sex steroid-binding protein of human plasma. FEBS Lett. 1987 Jul 27;219(2):405-9. [PubMed Link Image]
  8. Gershagen S, Fernlund P, Lundwall A: A cDNA coding for human sex hormone binding globulin. Homology to vitamin K-dependent protein S. FEBS Lett. 1987 Aug 10;220(1):129-35. [PubMed Link Image]
  9. Walsh KA, Titani K, Takio K, Kumar S, Hayes R, Petra PH: Amino acid sequence of the sex steroid binding protein of human blood plasma. Biochemistry. 1986 Nov 18;25(23):7584-90. [PubMed Link Image]
  10. Hammond GL, Underhill DA, Smith CL, Goping IS, Harley MJ, Musto NA, Cheng CY, Bardin CW: The cDNA-deduced primary structure of human sex hormone-binding globulin and location of its steroid-binding domain. FEBS Lett. 1987 May 4;215(1):100-4. [PubMed Link Image]
  11. 3702459 Hammond GL, Robinson PA, Sugino H, Ward DN, Finne J: Physicochemical characteristics of human sex hormone binding globulin: evidence for two identical subunits. J Steroid Biochem. 1986 Apr;24(4):815-24.
  12. 7714097 Hardy DO, Carino C, Catterall JF, Larrea F: Molecular characterization of a genetic variant of the steroid hormone-binding globulin gene in heterozygous subjects. J Clin Endocrinol Metab. 1995 Apr;80(4):1253-6.
Target 3 Drug References
  1. Nader N, Raverot G, Emptoz-Bonneton A, Dechaud H, Bonnay M, Baudin E, Pugeat M: Mitotane has an estrogenic effect on sex hormone-binding globulin and corticosteroid-binding globulin in humans. J Clin Endocrinol Metab. 2006 Jun;91(6):2165-70. Epub 2006 Mar 21. [PubMed Link Image]
  2. van Seters AP, Moolenaar AJ: Mitotane increases the blood levels of hormone-binding proteins. Acta Endocrinol (Copenh). 1991 May;124(5):526-33. [PubMed Link Image]
Drug Target 4 [top]
Target 4 ID 805
Target 4 Name Cytochrome P450 11B1, mitochondrial
Target 4 Synonyms
  1. CYPXIB1
  2. Cytochrome P450 11B1, mitochondrial precursor
  3. EC 1.14.15.4
  4. P-450c11
  5. P450C11
  6. Steroid 11-beta-hydroxylase
Target 4 Gene Name CYP11B1
Target 4 Protein Sequence >Cytochrome P450 11B1, mitochondrial precursor 
MALRAKAEVCMAVPWLSLQRAQALGTRAARVPRTVLPFEAMPQRPGNRWLRLLQIWREQG
YEDLHLEVHQTFQELGPIFRYDLGGAGMVCVMLPEDVEKLQQVDSLHPHRMSLEPWVAYR
QHRGHKCGVFLLNGPEWRFNRLRLNPEVLSPNAVQRFLPMVDAVARDFSQALKKKVLQNA
RGSLTLDVQPSIFHYTIEASNLALFGERLGLVGHSPSSASLNFLHALEVMFKSTVQLMFM
PRSLSRWTSPKVWKEHFEAWDCIFQYGDNCIQKIYQELAFSRPQQYTSIVAELLLNAELS
PDAIKANSMELTAGSVDTTVFPLLMTLFELARNPNVQQALRQESLAAAASISEHPQKATT
ELPLLRAALKETLRLYPVGLFLERVVSSDLVLQNYHIPAGTLVRVFLYSLGRNPALFPRP
ERYNPQRWLDIRGSGRNFYHVPFGFGMRQCLGRRLAEAEMLLLLHHVLKHLQVETLTQED
IKMVYSFILRPSMCPLLTFRAIN
Target 4 Number of Residues 511
Target 4 Molecular Weight 57530
Target 4 Theoretical pI 9.42
Target 4 GO Classification
Function
tetrapyrrole binding
heme binding
binding
ion binding
cation binding
transition metal ion binding
iron ion binding
catalytic activity
oxidoreductase activity
monooxygenase activity
Process
physiological process
metabolism
cellular metabolism
generation of precursor metabolites and energy
electron transport
Component
Not Available
Target 4 General Function Secondary metabolites biosynthesis, transport and catabolism
Target 4 Specific Function Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochrome P450 XIB
Target 4 Pathways
Name SMPDB Link KEGG Link
Androgen and estrogen metabolism SMP00068 Link Image map00150 Link Image
C21-Steroid hormone metabolism map00140 Link Image
Target 4 Reactions
  • a steroid + reduced adrenal ferredoxin + O2 = an 11beta-hydroxysteroid + oxidized adrenal ferredoxin + H2O
Target 4 Pfam Domain Function
Target 4 Signals
  • None
Target 4 Transmembrane Regions
  • None
Target 4 Essentiality Non-Essential
Target 4 GenBank ID Protein 181333 Link Image
Target 4 UniProtKB/Swiss-Prot ID P15538 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name C11B1_HUMAN Link Image
Target 4 PDB ID Not Available
Target 4 Cellular Location
  • Mitochondrion
Target 4 Gene Sequence >1512 bp 
ATGGCACTCAGGGCAAAGGCAGAGGTGTGCATGGCAGTGCCCTGGCTGTCCCTGCAAAGG
GCACAGGCACTGGGCACGAGAGCCGCCCGGGTCCCCAGGACAGTGCTGCCCTTTGAAGCC
ATGCCCCGGCGTCCAGGCAACAGGTGGCTGAGGCTGCTGCAGATCTGGAGGGAGCAGGGT
TATGAGGACCTGCACCTGGAAGTACACCAGACCTTCCAGGAACTGGGGCCCATTTTCAGG
TACGATTTGGGAGGAGCAGGCATGGTGTGTGTGATGCTGCCGGAGGACGTGGAGAAGCTG
CAACAGGTGGACAGCCTGCATCCCCACAGGATGAGCCTGGAGCCCTGGGTGGCCTACAGA
CAACATCGTGGGCACAAATGTGGCGTGTTCTTGCTGAATGGGCCTGAATGGCGCTTCAAC
CGATTGCGGCTGAATCCAGAAGTGCTGTCGCCCAACGCTGTGCAGAGGTTCCTCCCGATG
GTGGATGCAGTGGCCAGGGACTTCTCCCAGGCCCTGAAGAAGAAGGTGCTGCAGAACGCC
CGGGGGAGCCTGACCCTGGACGTCCAGCCCAGCATCTTCCACTACACCATAGAAGCCAGC
AACTTGGCTCTTTTTGGAGAGCGGCTGGGCCTGGTTGGCCACAGCCCCAGTTCTGCCAGC
CTGAACTTCCTCCATGCCCTGGAGGTCATGTTCAAATCCACCGTCCAGCTCATGTTCATG
CCCAGGAGCCTGTCTCGCTGGACCAGCCCCAAGGTGTGGAAGGAGCACTTTGAGGCCTGG
GACTGCATCTTCCAGTACGGCGACAACTGTATCCAGAAAATCTATCAGGAACTGGCCTTC
AGCCGCCCTCAACAGTACACCAGCATCGTGGCGGAGCTCCTGTTGAATGCGGAACTGTCG
CCAGATGCCATCAAGGCCAACTCTATGGAACTCACTGCAGGGAGCGTGGACACGACGGTG
TTTCCCTTGCTGATGACGCTCTTTGAGCTGGCTCGGAACCCCAACGTGCAGCAGGCCCTG
CGCCAGGAGAGCCTGGCCGCCGCAGCCAGCATCAGTGAACATCCCCAGAAGGCAACCACC
GAGCTGCCCTTGCTGCGTGCGGCCCTCAAGGAGACCTTGCGGCTCTACCCTGTGGGTCTG
TTTCTGGAGCGAGTGGCGAGCTCAGACTTGGTGCTTCAGAACTACCACATCCCAGCTGGG
ACATTGGTGCGCGTGTTCCTCTACTCTCTGGGTCGCAACCCCGCCTTGTTCCCGAGGCCT
GAGCGCTATAACCCCCAGCGCTGGCTAGACATCAGGGGCTCCGGCAGGAACTTCTACCAC
GTGCCCTTTGGCTTTGGCATGCGCCAGTGCCTTGGGCGGCGCCTGGCAGAGGCAGAGATG
CTGCTGCTGCTGCACCATGTGCTGAAACACCTCCAGGTGGAGACACTAACCCAAGAGGAC
ATAAAGATGGTCTACAGCTTCATATTGAGGCCCAGCATGTGCCCCCTCCTCACCTTCAGA
GCCATCAACTAA
Target 4 GenBank Gene ID
Target 4 GeneCard ID CYP11B1 Link Image
Target 4 GenAtlas ID CYP11B1 Link Image
Target 4 HGNC ID HGNC:2591 Link Image
Target 4 Chromosome Location 8
Target 4 Locus 8q21
Target 4 SNPs SNPJam Report Link Image
Target 4 General References
  1. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed Link Image]
  2. Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, Cooper R, Lipshutz R, Chakravarti A: Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nat Genet. 1999 Jul;22(3):239-47. [PubMed Link Image]
  3. Loidi L, Quinteiro C, Barros F, Dominguez F, Barreiro J, Pombo M: The C494F variant in the CYP11B1 gene is a sequence polymorphism in the Spanish population. J Clin Endocrinol Metab. 1999 Dec;84(12):4749. [PubMed Link Image]
  4. Kawamoto T, Mitsuuchi Y, Toda K, Yokoyama Y, Miyahara K, Miura S, Ohnishi T, Ichikawa Y, Nakao K, Imura H, et al.: Role of steroid 11 beta-hydroxylase and steroid 18-hydroxylase in the biosynthesis of glucocorticoids and mineralocorticoids in humans. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1458-62. [PubMed Link Image]
  5. White PC, Dupont J, New MI, Leiberman E, Hochberg Z, Rosler A: A mutation in CYP11B1 (Arg-448----His) associated with steroid 11 beta-hydroxylase deficiency in Jews of Moroccan origin. J Clin Invest. 1991 May;87(5):1664-7. [PubMed Link Image]
  6. Kawamoto T, Mitsuuchi Y, Toda K, Miyahara K, Yokoyama Y, Nakao K, Hosoda K, Yamamoto Y, Imura H, Shizuta Y: Cloning of cDNA and genomic DNA for human cytochrome P-45011 beta. FEBS Lett. 1990 Sep 3;269(2):345-9. [PubMed Link Image]
  7. Mornet E, Dupont J, Vitek A, White PC: Characterization of two genes encoding human steroid 11 beta-hydroxylase (P-450(11) beta). J Biol Chem. 1989 Dec 15;264(35):20961-7. [PubMed Link Image]
  8. Chua SC, Szabo P, Vitek A, Grzeschik KH, John M, White PC: Cloning of cDNA encoding steroid 11 beta-hydroxylase (P450c11). Proc Natl Acad Sci U S A. 1987 Oct;84(20):7193-7. [PubMed Link Image]
  9. Naiki Y, Kawamoto T, Mitsuuchi Y, Miyahara K, Toda K, Orii T, Imura H, Shizuta Y: A nonsense mutation (TGG [Trp116]-->TAG [Stop]) in CYP11B1 causes steroid 11 beta-hydroxylase deficiency. J Clin Endocrinol Metab. 1993 Dec;77(6):1677-82. [PubMed Link Image]
  10. Joehrer K, Geley S, Strasser-Wozak EM, Azziz R, Wollmann HA, Schmitt K, Kofler R, White PC: CYP11B1 mutations causing non-classic adrenal hyperplasia due to 11 beta-hydroxylase deficiency. Hum Mol Genet. 1997 Oct;6(11):1829-34. [PubMed Link Image]
Target 4 Drug References
  1. 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 Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.