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Showing drug card for Trilostane (DB01108)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:04:35
Primary Accession Number DB01108
Secondary Accession Number
  • APRD01276
Name Trilostane
Drug Type
  • Approved
  • Investigational
  • Small Molecule
  • Withdrawn
Description Trilostane is an inhibitor of 3 beta-hydroxysteroid dehydrogenase used in the treatment of Cushing's syndrome. It was withdrawn from the United States market in April 1994. [Wikipedia]
Synonyms
  1. trilostane
Brand Names
  1. Desopan
  2. Modrastane
  3. Modrenal
Brand Mixtures Not Available
Chemical IUPAC Name Not Available
Chemical Formula C20H27NO3
Chemical Structure Structure
CAS Registry Number 13647-35-3
InChI Identifier InChI=1/C20H27NO3/c1-18-7-6-14-12(13(18)3-4-15(18)22)5-8-20-17(24-20)16(23)11(10-21)9-19(14,20)2/h12-15,17,22-23H,3-9H2,1-2H3/t12-,13-,14-,15-,17+,18-,19+,20+/m0/s1
InChI Key KVJXBPDAXMEYOA-CXANFOAXBX
KEGG Drug D01180 Link Image
KEGG Compound Not Available
PubChem Compound 656583 Link Image
PubChem Substance 7848243 Link Image
ChEBI ID Not Available
PharmGKB ID PA451780 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] Not Available
RxList Link Not Available
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Trilostane Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 329.4333
Monoisotopic Molecular Weight 329.1991
State Solid
Melting Point 264 oC
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility 5.92e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 3 Source: PhysProp
Predicted LogP 2.42 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -3.75 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 C[C@]12CC[C@H]3[C@@H](CC[C@@]45O[C@@H]4C(O)=C(C[C@]35C)C#N)[C@@H]1CC[C@@H]2O
Canonical SMILES CC12CCC3C(CCC45OC4C(O)=C(CC35C)C#N)C1CCC2O
Drug Category
  • Antiadrenal
  • Anticorticosteroids
ATC Codes
AHFS Codes Not Available
Indication Used in the treatment of Cushing's syndrome. It is normally used in short-term treatment until permanent therapy is possible.
Pharmacology Trilostane blocks an enzyme involved in the production of several steroids including cortisol. Inhibiting this enzyme inhibits the production of cortisol. In Cushing's syndrome, the adrenal gland overproduces steroids. Although steroids are important for various functions of the body, too much can cause problems. Trilostane reduces the amount of steroids produced by the adrenal gland. This product was withdrawn from the U.S. market in April 1994.
Mechanism of Action Trilostane produces suppression of the adrenal cortex by inhibiting enzymatic conversion of steroids by 3-beta-hydroxysteroid dehydrogenase/delta 5,4 ketosteroid isomerase, thus blocking synthesis of adrenal steroids.
Absorption Not Available
Toxicity Symptoms of overdose include darkening of skin, drowsiness or tiredness, loss of appetite, mental depression, skin rash, and/or vomiting.
Protein Binding Not Available
Biotransformation Hepatic.
Half Life 8 hours.
Dosage Forms Not Available
Patient Information Not Available
Contraindications Not Available
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. Komanicky P, Spark RF, Melby JC: Treatment of Cushing's syndrome with trilostane (WIN 24,540), an inhibitor of adrenal steroid biosynthesis. J Clin Endocrinol Metab. 1978 Nov;47(5):1042-51. [PubMed Link Image]
  2. Drugs.com Link Image
  3. Wikipedia Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 11A1 (CYP11A1)
Targets
  1. 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type I
  2. 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type II
  3. Estrogen receptor beta
  4. Corticotropin-lipotropin
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 11A1 (CYP11A1)
Enzyme 1 Gene Name CYP11A1
Enzyme 1 SwissProt ID P05108 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P05108|C11A_HUMAN Cytochrome P450 11A1 
MLAKGLPPRSVLVKGYQTFLSAPREGLGRLRVPTGEGAGISTRSPRPFNEIPSPGDNGWL
NLYHFWRETGTHKVHLHHVQNFQKYGPIYREKLGNVESVYVIDPEDVALLFKSEGPNPER
FLIPPWVAYHQYYQRPIGVLLKKSAAWKKDRVALNQEVMAPEATKNFLPLLDAVSRDFVS
VLHRRIKKAGSGNYSGDISDDLFRFAFESITNVIFGERQGMLEEVVNPEAQRFIDAIYQM
FHTSVPMLNLPPDLFRLFRTKTWKDHVAAWDVIFSKADIYTQNFYWELRQKGSVHHDYRG
MLYRLLGDSKMSFEDIKANVTEMLAGGVDTTSMTLQWHLYEMARNLKVQDMLRAEVLAAR
HQAQGDMATMLQLVPLLKASIKETLRLHPISVTLQRYLVNDLVLRDYMIPAKTLVQVAIY
ALGREPTFFFDPENFDPTRWLSKDKNITYFRNLGFGWGVRQCLGRRIAELEMTIFLINML
ENFRVEIQHLSDVGTTFNLILMPEKPISFTFWPFNQEATQQ
Drug Target 1 [top]
Target 1 ID 57
Target 1 Name 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type I
Target 1 Synonyms
  1. 3- beta-HSD I
  2. 3-beta-hydroxy-5-ene steroid dehydrogenase
  3. 3-beta-hydroxy-Delta(5)-steroid dehydrogenase
  4. Delta-5-3-ketosteroid isomerase
  5. EC 1.1.1.145
  6. EC 5.3.3.1
  7. Progesterone reductase
  8. Steroid Delta- isomerase
  9. Trophoblast antigen FDO161G
Target 1 Gene Name HSD3B1
Target 1 Protein Sequence >4-isomerase type I 
TGWSCLVTGAGGFLGQRIIRLLVKEKELKEIRVLDKAFGPELREEFSKLQNKTKLTVLEG
DILDEPFLKRACQDVSVIIHTACIIDVFGVTHRESIMNVNVKGTQLLLEACVQASVPVFI
YTSSIEVAGPNSYKEIIQNGHEEEPLENTWPAPYPHSKKLAEKAVLAANGWNLKNGGTLY
TCALRPMYIYGEGSRFLSASINEALNNNGILSSVGKFSTVNPVYVGNVAWAHILALRALQ
DPKKAPSIRGQFYYISDDTPHQSYDNLNYTLSKEFGLRLDSRWSFPLSLMYWIGFLLEIV
SFLLRPIYTYRPPFNRHIVTLSNSVFTFSYKKAQRDLAYKPLYSWEEAKQKTVEWVGSLV
DRHKETLKSKTQ
Target 1 Number of Residues 378
Target 1 Molecular Weight 42121
Target 1 Theoretical pI 8.98
Target 1 GO Classification
Function
isomerase activity
intramolecular oxidoreductase activity
intramolecular oxidoreductase activity, transposing C=C bonds
steroid delta-isomerase activity
catalytic activity
oxidoreductase activity
oxidoreductase activity, acting on CH-OH group of donors
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
steroid dehydrogenase activity
3-beta-hydroxy-delta5-steroid dehydrogenase activity
Process
physiological process
metabolism
primary metabolism
lipid metabolism
cellular lipid metabolism
steroid metabolism
steroid biosynthesis
Component
Not Available
Target 1 General Function Cell wall/membrane/envelope biogenesis
Target 1 Specific Function 3beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids
Target 1 Pathways
Name SMPDB Link KEGG Link
Androgen and estrogen metabolism SMP00068 Link Image map00150 Link Image
C21-Steroid hormone metabolism map00140 Link Image
Target 1 Reactions
  • a 3beta-hydroxy-Delta5-steroid + NAD+ = a 3-oxo-Delta5-steroid + NADH + H+
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 287-307
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 306889 Link Image
Target 1 UniProtKB/Swiss-Prot ID P14060 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name 3BHS1_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Endoplasmic reticulum
  • endoplasmic reticulum membrane
  • single-pass membrane protein. Mitochondrion
Target 1 Gene Sequence >1122 bp 
ATGACGGGCTGGAGCTGCCTTGTGACAGGAGCAGGAGGGTTTCTGGGACAGAGGATCATC
CGCCTCTTGGTGAAGGAGAAGGAGCTGAAGGAGATCAGGGTCTTGGACAAGGCCTTCGGA
CCAGAATTGAGAGAGGAATTTTCTAAACTCCAGAACAAGACCAAGCTGACAGTGCTGGAA
GGAGACATTCTGGATGAGCCATTCCTGAAGAGAGCCTGCCAGGACGTCTCGGTCATCATC
CACACCGCCTGTATCATTGATGTCTTCGGTGTCACTCACAGAGAGTCTATCATGAATGTC
AATGTGAAAGGTACCCAGCTCCTGTTAGAGGCCTGTGTCCAAGCTAGTGTGCCAGTCTTC
ATCTACACCAGTAGCATAGAGGTAGCCGGGCCCAACTCCTACAAGGAAATCATCCAGAAT
GGCCATGAAGAAGAGCCTCTGGAAAACACATGGCCCGCTCCATACCCACACAGCAAAAAG
CTTGCTGAGAAGGCTGTACTGGCGGCTAACGGGTGGAATCTGAAAAACGGCGGCACCCTG
TACACTTGTGCCTTACGACCCATGTATATCTATGGGGAAGGAAGCCGATTCCTTTCTGCT
AGTATAAACGAGGCCCTGAACAACAATGGGATCCTGTCAAGTGTTGGAAAGTTCTCCACT
GTTAACCCAGTCTATGTTGGCAATGTGGCCTGGGCCCACATTCTGGCCTTGAGGGCCCTG
CAGGACCCCAAGAAGGCCCCAAGCATCCGAGGACAGTTCTACTATATCTCAGATGACACG
CCTCACCAAAGCTATGATAACCTTAATTACACCCTGAGCAAAGAGTTCGGCCTCCGCCTT
GATTCCAGATGGAGCTTTCCTTTATCCCTGATGTATTGGATTGGCTTCCTGCTGGAAATA
GTGAGCTTCCTACTCAGGCCAATTTACACCTATCGACCGCCCTTCAACCGCCACATAGTC
ACATTGTCAAATAGCGTATTCACCTTCTCTTATAAGAAGGCTCAGCGAGATCTGGCGTAT
AAGCCACTCTACAGCTGGGAGGAAGCCAAGCAGAAAACGGTGGAGTGGGTTGGTTCCCTT
GTGGACCGGCACAAGGAGACCCTGAAGTCCAAGACTCAGTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID HSD3B1 Link Image
Target 1 GenAtlas ID HSD3B1 Link Image
Target 1 HGNC ID HGNC:5217 Link Image
Target 1 Chromosome Location 1
Target 1 Locus 1p13.1
Target 1 SNPs SNPJam Report Link Image
Target 1 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. Dumont M, Luu-The V, Dupont E, Pelletier G, Labrie F: Characterization, expression, and immunohistochemical localization of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase in human skin. J Invest Dermatol. 1992 Oct;99(4):415-21. [PubMed Link Image]
  3. Nickson DA, McBride MW, Zeinali S, Hawes CS, Petropoulos A, Mueller UW, Sutcliffe RG: Molecular cloning and expression of human trophoblast antigen FDO161G and its identification as 3 beta-hydroxy-5-ene steroid dehydrogenase. J Reprod Fertil. 1991 Sep;93(1):149-56. [PubMed Link Image]
  4. Lorence MC, Corbin CJ, Kamimura N, Mahendroo MS, Mason JI: Structural analysis of the gene encoding human 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase. Mol Endocrinol. 1990 Dec;4(12):1850-5. [PubMed Link Image]
  5. Lorence MC, Murry BA, Trant JM, Mason JI: Human 3 beta-hydroxysteroid dehydrogenase/delta 5----4isomerase from placenta: expression in nonsteroidogenic cells of a protein that catalyzes the dehydrogenation/isomerization of C21 and C19 steroids. Endocrinology. 1990 May;126(5):2493-8. [PubMed Link Image]
  6. Lachance Y, Luu-The V, Labrie C, Simard J, Dumont M, de Launoit Y, Guerin S, Leblanc G, Labrie F: Characterization of human 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase gene and its expression in mammalian cells. J Biol Chem. 1990 Nov 25;265(33):20469-75. [PubMed Link Image]
  7. Luu The V, Lachance Y, Labrie C, Leblanc G, Thomas JL, Strickler RC, Labrie F: Full length cDNA structure and deduced amino acid sequence of human 3 beta-hydroxy-5-ene steroid dehydrogenase. Mol Endocrinol. 1989 Aug;3(8):1310-2. [PubMed Link Image]
Target 1 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
  3. Naville D, Keeney DS, Jenkin G, Murry BA, Head JR, Mason JI: Regulation of expression of male-specific rat liver microsomal 3 beta-hydroxysteroid dehydrogenase. Mol Endocrinol. 1991 Aug;5(8):1090-100. [PubMed Link Image]
  4. Cooke GM: Differential effects of trilostane and cyanoketone on the 3 beta-hydroxysteroid dehydrogenase-isomerase reactions in androgen and 16-androstene biosynthetic pathways in the pig testis. J Steroid Biochem Mol Biol. 1996 Apr;58(1):95-101. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 66
Target 2 Name 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type II
Target 2 Synonyms
  1. 3-beta-hydroxy-5-ene steroid dehydrogenase
  2. 3-beta-hydroxy-Delta(5)-steroid dehydrogenase
  3. EC 1.1.1.145
  4. EC 5.3.3.1
  5. Progesterone reductase
  6. Steroid Delta-isomerase
Target 2 Gene Name HSD3B2
Target 2 Protein Sequence >4-isomerase type II 
GWSCLVTGAGGLLGQRIVRLLVEEKELKEIRALDKAFRPELREEFSKLQNRTKLTVLEGD
ILDEPFLKRACQDVSVVIHTACIIDVFGVTHRESIMNVNVKGTQLLLEACVQASVPVFIY
TSSIEVAGPNSYKEIIQNGHEEEPLENTWPTPYPYSKKLAEKAVLAANGWNLKNGDTLYT
CALRPTYIYGEGGPFLSASINEALNNNGILSSVGKFSTVNPVYVGNVAWAHILALRALRD
PKKAPSVRGQFYYISDDTPHQSYDNLNYILSKEFGLRLDSRWSLPLTLMYWIGFLLEVVS
FLLSPIYSYQPPFNRHTVTLSNSVFTFSYKKAQRDLAYKPLYSWEEAKQKTVEWVGSLVD
RHKETLKSKTQ
Target 2 Number of Residues 377
Target 2 Molecular Weight 41921
Target 2 Theoretical pI 8.17
Target 2 GO Classification
Function
isomerase activity
intramolecular oxidoreductase activity
intramolecular oxidoreductase activity, transposing C=C bonds
steroid delta-isomerase activity
catalytic activity
oxidoreductase activity
oxidoreductase activity, acting on CH-OH group of donors
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
steroid dehydrogenase activity
3-beta-hydroxy-delta5-steroid dehydrogenase activity
Process
physiological process
metabolism
primary metabolism
lipid metabolism
cellular lipid metabolism
steroid metabolism
steroid biosynthesis
Component
Not Available
Target 2 General Function Cell wall/membrane/envelope biogenesis
Target 2 Specific Function 3beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids
Target 2 Pathways
Name SMPDB Link KEGG Link
Androgen and estrogen metabolism SMP00068 Link Image map00150 Link Image
C21-Steroid hormone metabolism map00140 Link Image
Target 2 Reactions
  • a 3beta-hydroxy-Delta5-steroid + NAD+ = a 3-oxo-Delta5-steroid + NADH + H+
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 286-306
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 184401 Link Image
Target 2 UniProtKB/Swiss-Prot ID P26439 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name 3BHS2_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Endoplasmic reticulum
  • endoplasmic reticulum membrane
  • single-pass membrane protein. Mitochondrion
Target 2 Gene Sequence >1119 bp 
ATGGGCTGGAGCTGCCTTGTGACAGGAGCAGGAGGGCTTCTGGGTCAGAGGATCGTCCGC
CTGTTGGTGGAAGAGAAGGAACTGAAGGAGATCAGGGCCTTGGACAAGGCCTTCAGACCA
GAATTGAGAGAGGAATTTTCTAAGCTCCAGAACAGGACCAAGCTGACTGTACTTGAAGGA
GACATTCTGGATGAGCCATTCCTGAAAAGAGCCTGCCAGGACGTCTCGGTCGTCATCCAC
ACCGCCTGTATCATTGATGTCTTTGGTGTCACTCACAGAGAGTCCATCATGAATGTCAAT
GTGAAAGGTACCCAGCTACTGTTGGAGGCCTGTGTCCAAGCCAGTGTGCCAGTCTTCATC
TACACCAGTAGCATAGAGGTAGCCGGGCCCAACTCCTACAAGGAAATCATCCAGAACGGC
CACGAAGAAGAGCCTCTGGAAAACACATGGCCCACTCCATACCCGTACAGCAAAAAGCTT
GCTGAGAAGGCTGTGCTGGCGGCTAATGGGTGGAATCTAAAAAATGGTGATACCTTGTAC
ACTTGTGCGTTAAGACCCACATATATCTATGGGGAAGGAGGCCCATTCCTTTCTGCCAGT
ATAAATGAGGCCCTGAACAACAATGGGATCCTGTCAAGTGTTGGAAAGTTCTCTACAGTC
AACCCAGTCTATGTTGGCAACGTGGCCTGGGCCCACATTCTGGCCTTGAGGGCTCTGCGG
GACCCCAAGAAGGCCCCAAGTGTCCGAGGTCAATTCTATTACATCTCAGATGACACGCCT
CACCAAAGCTATGATAACCTTAATTACATCCTGAGCAAAGAGTTTGGCCTCCGCCTTGAT
TCCAGATGGAGCCTTCCTTTAACCCTGATGTACTGGATTGGCTTCCTGCTGGAAGTAGTG
AGCTTCCTACTCAGCCCAATTTACTCCTATCAACCCCCCTTCAACCGCCACACAGTCACA
TTATCAAATAGTGTGTTCACCTTCTCTTACAAGAAGGCTCAGCGAGATCTGGCGTATAAG
CCACTCTACAGCTGGGAGGAAGCCAAGCAGAAAACCGTGGAGTGGGTTGGTTCCCTTGTG
GACCGGCACAAGGAGACCCTGAAGTCCAAGACTCAGTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID HSD3B2 Link Image
Target 2 GenAtlas ID HSD3B2 Link Image
Target 2 HGNC ID HGNC:5218 Link Image
Target 2 Chromosome Location 1
Target 2 Locus 1p13.1
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Moisan AM, Ricketts ML, Tardy V, Desrochers M, Mebarki F, Chaussain JL, Cabrol S, Raux-Demay MC, Forest MG, Sippell WG, Peter M, Morel Y, Simard J: New insight into the molecular basis of 3beta-hydroxysteroid dehydrogenase deficiency: identification of eight mutations in the HSD3B2 gene eleven patients from seven new families and comparison of the functional properties of twenty-five mutant enzymes. J Clin Endocrinol Metab. 1999 Dec;84(12):4410-25. [PubMed Link Image]
  2. Marui S, Castro M, Latronico AC, Elias LL, Arnhold IJ, Moreira AC, Mendonca BB: Mutations in the type II 3beta-hydroxysteroid dehydrogenase (HSD3B2) gene can cause premature pubarche in girls. Clin Endocrinol (Oxf). 2000 Jan;52(1):67-75. [PubMed Link Image]
  3. Alos N, Moisan AM, Ward L, Desrochers M, Legault L, Leboeuf G, Van Vliet G, Simard J: A novel A10E homozygous mutation in the HSD3B2 gene causing severe salt-wasting 3beta-hydroxysteroid dehydrogenase deficiency in 46,XX and 46,XY French-Canadians: evaluation of gonadal function after puberty. J Clin Endocrinol Metab. 2000 May;85(5):1968-74. [PubMed Link Image]
  4. Pang S, Wang W, Rich B, David R, Chang YT, Carbunaru G, Myers SE, Howie AF, Smillie KJ, Mason JI: A novel nonstop mutation in the stop codon and a novel missense mutation in the type II 3beta-hydroxysteroid dehydrogenase (3beta-HSD) gene causing, respectively, nonclassic and classic 3beta-HSD deficiency congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2002 Jun;87(6):2556-63. [PubMed Link Image]
  5. Lachance Y, Luu-The V, Verreault H, Dumont M, Rheaume E, Leblanc G, Labrie F: Structure of the human type II 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) gene: adrenal and gonadal specificity. DNA Cell Biol. 1991 Dec;10(10):701-11. [PubMed Link Image]
  6. Rheaume E, Lachance Y, Zhao HF, Breton N, Dumont M, de Launoit Y, Trudel C, Luu-The V, Simard J, Labrie F: Structure and expression of a new complementary DNA encoding the almost exclusive 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase in human adrenals and gonads. Mol Endocrinol. 1991 Aug;5(8):1147-57. [PubMed Link Image]
  7. Mebarki F, Sanchez R, Rheaume E, Laflamme N, Simard J, Forest MG, Bey-Omar F, David M, Labrie F, Morel Y: Nonsalt-losing male pseudohermaphroditism due to the novel homozygous N100S mutation in the type II 3 beta-hydroxysteroid dehydrogenase gene. J Clin Endocrinol Metab. 1995 Jul;80(7):2127-34. [PubMed Link Image]
  8. Katsumata N, Tanae A, Yasunaga T, Horikawa R, Tanaka T, Hibi I: A novel missense mutation in the type II 3 beta-hydroxysteroid dehydrogenase gene in a family with classical salt-wasting congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency. Hum Mol Genet. 1995 Apr;4(4):745-6. [PubMed Link Image]
  9. Tajima T, Fujieda K, Nakae J, Shinohara N, Yoshimoto M, Baba T, Kinoshita E, Igarashi Y, Oomura T: Molecular analysis of type II 3 beta-hydroxysteroid dehydrogenase gene in Japanese patients with classical 3 beta-hydroxysteroid dehydrogenase deficiency. Hum Mol Genet. 1995 May;4(5):969-71. [PubMed Link Image]
  10. Sanchez R, Mebarki F, Rheaume E, Laflamme N, Forest MG, Bey-Omard F, David M, Morel Y, Labrie F, Simard J: Functional characterization of the novel L108W and P186L mutations detected in the type II 3 beta-hydroxysteroid dehydrogenase gene of a male pseudohermaphrodite with congenital adrenal hyperplasia. Hum Mol Genet. 1994 Sep;3(9):1639-45. [PubMed Link Image]
  11. 7893703 Rheaume E, Sanchez R, Mebarki F, Gagnon E, Carel JC, Chaussain JL, Morel Y, Labrie F, Simard J: Identification and characterization of the G15D mutation found in a male patient with 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency: alteration of the putative NAD-binding domain of type II 3 beta-HSD. Biochemistry. 1995 Mar 7;34(9):2893-900.
  12. 7962268 Rheaume E, Sanchez R, Simard J, Chang YT, Wang J, Pang S, Labrie F: Molecular basis of congenital adrenal hyperplasia in two siblings with classical nonsalt-losing 3 beta-hydroxysteroid dehydrogenase deficiency. J Clin Endocrinol Metab. 1994 Oct;79(4):1012-8.
  13. 8060486 Russell AJ, Wallace AM, Forest MG, Donaldson MD, Edwards CR, Sutcliffe RG: Mutation in the human gene for 3 beta-hydroxysteroid dehydrogenase type II leading to male pseudohermaphroditism without salt loss. J Mol Endocrinol. 1994 Apr;12(2):225-37.
  14. 8126127 Sanchez R, Rheaume E, Laflamme N, Rosenfield RL, Labrie F, Simard J: Detection and functional characterization of the novel missense mutation Y254D in type II 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) gene of a female patient with nonsalt-losing 3 beta HSD deficiency. J Clin Endocrinol Metab. 1994 Mar;78(3):561-7.
  15. 8185809 Mendonca BB, Russell AJ, Vasconcelos-Leite M, Arnhold IJ, Bloise W, Wajchenberg BL, Nicolau W, Sutcliffe RG, Wallace AM: Mutation in 3 beta-hydroxysteroid dehydrogenase type II associated with pseudohermaphroditism in males and premature pubarche or cryptic expression in females. J Mol Endocrinol. 1994 Feb;12(1):119-22.
  16. 8316254 Simard J, Rheaume E, Sanchez R, Laflamme N, de Launoit Y, Luu-The V, van Seters AP, Gordon RD, Bettendorf M, Heinrich U, et al.: Molecular basis of congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency. Mol Endocrinol. 1993 May;7(5):716-28.
  17. 9719627 Nayak S, Lee PA, Witchel SF: Variants of the type II 3beta-hydroxysteroid dehydrogenase gene in children with premature pubic hair and hyperandrogenic adolescents. Mol Genet Metab. 1998 Jul;64(3):184-92.
Target 2 Drug References
  1. Naville D, Keeney DS, Jenkin G, Murry BA, Head JR, Mason JI: Regulation of expression of male-specific rat liver microsomal 3 beta-hydroxysteroid dehydrogenase. Mol Endocrinol. 1991 Aug;5(8):1090-100. [PubMed Link Image]
  2. Takahashi M, Luu-The V, Labrie F: Inhibitory effect of synthetic progestins, 4-MA and cyanoketone on human placental 3 beta-hydroxysteroid dehydrogenase/5----4-ene-isomerase activity. J Steroid Biochem Mol Biol. 1990 Oct;37(2):231-6. [PubMed Link Image]
  3. Suzuki S, Endo Y, Tanaka S, Iizuka R: Indirect immunofluorescence studies on the steroid-producing activity of hamster ova. Am J Obstet Gynecol. 1984 Jan 1;148(1):76-85. [PubMed Link Image]
  4. Duffy DM, Hess DL, Stouffer RL: Acute administration of a 3 beta-hydroxysteroid dehydrogenase inhibitor to rhesus monkeys at the midluteal phase of the menstrual cycle: evidence for possible autocrine regulation of the primate corpus luteum by progesterone. J Clin Endocrinol Metab. 1994 Dec;79(6):1587-94. [PubMed Link Image]
  5. Mensah-Nyagan AG, Feuilloley M, Dupont E, Do-Rego JL, Leboulenger F, Pelletier G, Vaudry H: Immunocytochemical localization and biological activity of 3 beta-hydroxysteroid dehydrogenase in the central nervous system of the frog. J Neurosci. 1994 Dec;14(12):7306-18. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 869
Target 3 Name Estrogen receptor beta
Target 3 Synonyms
  1. ER-beta
Target 3 Gene Name ESR2
Target 3 Protein Sequence >Estrogen receptor beta 
MDIKNSPSSLNSPSSYNCSQSILPLEHGSIYIPSSYVDSHHEYPAMTFYSPAVMNYSIPS
NVTNLEGGPGRQTTSPNVLWPTPGHLSPLVVHRQLSHLYAEPQKSPWCEARSLEHTLPVN
RETLKRKVSGNRCASPVTGPGSKRDAHFCAVCSDYASGYHYGVWSCEGCKAFFKRSIQGH
NDYICPATNQCTIDKNRRKSCQACRLRKCYEVGMVKCGSRRERCGYRLVRRQRSADEQLH
CAGKAKRSGGHAPRVRELLLDALSPEQLVLTLLEAEPPHVLISRPSAPFTEASMMMSLTK
LADKELVHMISWAKKIPGFVELSLFDQVRLLESCWMEVLMMGLMWRSIDHPGKLIFAPDL
VLDRDEGKCVEGILEIFDMLLATTSRFRELKLQHKEYLCVKAMILLNSSMYPLVTATQDA
DSSRKLAHLLNAVTDALVWVIAKSGISSQQQSMRLANLLMLLSHVRHASNKGMEHLLNMK
CKNVVPVYDLLLEMLNAHVLRGCKSSITGSECSPAEDSKSKEGSQNPQSQ
Target 3 Number of Residues 538
Target 3 Molecular Weight 59217
Target 3 Theoretical pI 8.55
Target 3 GO Classification
Function
ion binding
cation binding
transition metal ion binding
zinc ion binding
steroid binding
signal transducer activity
receptor activity
ligand-dependent nuclear receptor activity
steroid hormone receptor activity
binding
nucleic acid binding
DNA binding
transcription factor activity
Process
regulation of biological process
regulation of physiological process
regulation of metabolism
regulation of cellular metabolism
regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism
regulation of transcription
regulation of transcription, DNA-dependent
Component
organelle
membrane-bound organelle
intracellular membrane-bound organelle
nucleus
Target 3 General Function Involved in transcription factor activity
Target 3 Specific Function Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA- binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 2911152 Link Image
Target 3 UniProtKB/Swiss-Prot ID Q92731 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name ESR2_HUMAN Link Image
Target 3 PDB ID 1QKM Link Image
Target 3 PDB File Show
Target 3 3D Structure
Target 3 Cellular Location
  • Nucleus
Target 3 Gene Sequence >1593 bp 
ATGGATATAAAAAACTCACCATCTAGCCTTAATTCTCCTTCCTCCTACAACTGCAGTCAA
TCCATCTTACCCCTGGAGCACGGCTCCATATACATACCTTCCTCCTATGTAGACAGCCAC
CATGAATATCCAGCCATGACATTCTATAGCCCTGCTGTGATGAATTACAGCATTCCCAGC
AATGTCACTAACTTGGAAGGTGGGCCTGGTCGGCAGACCACAAGCCCAAATGTGTTGTGG
CCAACACCTGGGCACCTTTCTCCTTTAGTGGTCCATCGCCAGTTATCACATCTGTATGCG
GAACCTCAAAAGAGTCCCTGGTGTGAAGCAAGATCGCTAGAACACACCTTACCTGTAAAC
AGAGAGACACTGAAAAGGAAGGTTAGTGGGAACCGTTGCGCCAGCCCTGTTACTGGTCCA
GGTTCAAAGAGGGATGCTCACTTCTGCGCTGTCTGCAGCGATTACGCATCGGGATATCAC
TATGGAGTCTGGTCGTGTGAAGGATGTAAGGCCTTTTTTAAAAGAAGCATTCAAGGACAT
AATGATTATATTTGTCCAGCTACAAATCAGTGTACAATCGATAAAAACCGGCGCAAGAGC
TGCCAGGCCTGCCGACTTCGGAAGTGTTACGAAGTGGGAATGGTGAAGTGTGGCTCCCGG
AGAGAGAGATGTGGGTACCGCCTTGTGCGGAGACAGAGAAGTGCCGACGAGCAGCTGCAC
TGTGCCGGCAAGGCCAAGAGAAGTGGCGGCCACGCGCCCCGAGTGCGGGAGCTGCTGCTG
GACGCCCTGAGCCCCGAGCAGCTAGTGCTCACCCTCCTGGAGGCTGAGCCGCCCCATGTG
CTGATCAGCCGCCCCAGTGCGCCCTTCACCGAGGCCTCCATGATGATGTCCCTGACCAAG
TTGGCCGACAAGGAGTTGGTACACATGATCAGCTGGGCCAAGAAGATTCCCGGCTTTGTG
GAGCTCAGCCTGTTCGACCAAGTGCGGCTCTTGGAGAGCTGTTGGATGGAGGTGTTAATG
ATGGGGCTGATGTGGCGCTCAATTGACCACCCCGGCAAGCTCATCTTTGCTCCAGATCTT
GTTCTGGACAGGGATGAGGGGAAATGCGTAGAAGGAATTCTGGAAATCTTTGACATGCTC
CTGGCAACTACTTCAAGGTTTCGAGAGTTAAAACTCCAACACAAAGAATATCTCTGTGTC
AAGGCCATGATCCTGCTCAATTCCAGTATGTACCCTCTGGTCACAGCGACCCAGGATGCT
GACAGCAGCCGGAAGCTGGCTCACTTGCTGAACGCCGTGACCGATGCTTTGGTTTGGGTG
ATTGCCAAGAGCGGCATCTCCTCCCAGCAGCAATCCATGCGCCTGGCTAACCTCCTGATG
CTCCTGTCCCACGTCAGGCATGCGAGTAACAAGGGCATGGAACATCTGCTCAACATGAAG
TGCAAAAATGTGGTCCCAGTGTATGACCTGCTGCTGGAGATGCTGAATGCCCACGTGCTT
CGCGGGTGCAAGTCCTCCATCACGGGGTCCGAGTGCAGCCCGGCAGAGGACAGTAAAAGC
AAAGAGGGCTCCCAGAACCCACAGTCTCAGTGA
Target 3 GenBank Gene ID
Target 3 GeneCard ID ESR2 Link Image
Target 3 GenAtlas ID ESR2 Link Image
Target 3 HGNC ID HGNC:3468 Link Image
Target 3 Chromosome Location 14
Target 3 Locus 14q23.2
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Caira F, Antonson P, Pelto-Huikko M, Treuter E, Gustafsson JA: Cloning and characterization of RAP250, a novel nuclear receptor coactivator. J Biol Chem. 2000 Feb 25;275(8):5308-17. [PubMed Link Image]
  2. Li LC, Yeh CC, Nojima D, Dahiya R: Cloning and characterization of human estrogen receptor beta promoter. Biochem Biophys Res Commun. 2000 Aug 28;275(2):682-9. [PubMed Link Image]
  3. Sauve F, McBroom LD, Gallant J, Moraitis AN, Labrie F, Giguere V: CIA, a novel estrogen receptor coactivator with a bifunctional nuclear receptor interacting determinant. Mol Cell Biol. 2001 Jan;21(1):343-53. [PubMed Link Image]
  4. Wong CW, McNally C, Nickbarg E, Komm BS, Cheskis BJ: Estrogen receptor-interacting protein that modulates its nongenomic activity-crosstalk with Src/Erk phosphorylation cascade. Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14783-8. Epub 2002 Nov 1. [PubMed Link Image]
  5. Mosselman S, Polman J, Dijkema R: ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett. 1996 Aug 19;392(1):49-53. [PubMed Link Image]
  6. Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM: Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell. 1997 Aug 8;90(3):569-80. [PubMed Link Image]
  7. Pace P, Taylor J, Suntharalingam S, Coombes RC, Ali S: Human estrogen receptor beta binds DNA in a manner similar to and dimerizes with estrogen receptor alpha. J Biol Chem. 1997 Oct 10;272(41):25832-8. [PubMed Link Image]
  8. Ogawa S, Inoue S, Watanabe T, Hiroi H, Orimo A, Hosoi T, Ouchi Y, Muramatsu M: The complete primary structure of human estrogen receptor beta (hER beta) and its heterodimerization with ER alpha in vivo and in vitro. Biochem Biophys Res Commun. 1998 Feb 4;243(1):122-6. [PubMed Link Image]
  9. Moore JT, McKee DD, Slentz-Kesler K, Moore LB, Jones SA, Horne EL, Su JL, Kliewer SA, Lehmann JM, Willson TM: Cloning and characterization of human estrogen receptor beta isoforms. Biochem Biophys Res Commun. 1998 Jun 9;247(1):75-8. [PubMed Link Image]
  10. Ogawa S, Inoue S, Watanabe T, Orimo A, Hosoi T, Ouchi Y, Muramatsu M: Molecular cloning and characterization of human estrogen receptor betacx: a potential inhibitor ofestrogen action in human. Nucleic Acids Res. 1998 Aug 1;26(15):3505-12. [PubMed Link Image]
  11. 9685228 Lu B, Leygue E, Dotzlaw H, Murphy LJ, Murphy LC, Watson PH: Estrogen receptor-beta mRNA variants in human and murine tissues. Mol Cell Endocrinol. 1998 Mar 16;138(1-2):199-203.
Target 3 Drug References
  1. Duffy DM, Chaffin CL, Stouffer RL: Expression of estrogen receptor alpha and beta in the rhesus monkey corpus luteum during the menstrual cycle: regulation by luteinizing hormone and progesterone. Endocrinology. 2000 May;141(5):1711-7. [PubMed Link Image]
  2. Barker S, Malouitre SD, Glover HR, Puddefoot JR, Vinson GP: Comparison of effects of 4-hydroxy tamoxifen and trilostane on oestrogen-regulated gene expression in MCF-7 cells: up-regulation of oestrogen receptor beta. J Steroid Biochem Mol Biol. 2006 Aug;100(4-5):141-51. Epub 2006 Jun 27. [PubMed Link Image]
Drug Target 4 [top]
Target 4 ID 1262
Target 4 Name Corticotropin-lipotropin
Target 4 Synonyms
  1. Corticotropin-lipotropin precursor
  2. POMC
  3. Pro-opiomelanocortin
Target 4 Gene Name POMC
Target 4 Protein Sequence >Corticotropin-lipotropin precursor 
MPRSCCSRSGALLLALLLQASMEVRGWCLESSQCQDLTTESNLLECIRACKPDLSAETPM
FPGNGDEQPLTENPRKYVMGHFRWDRFGRRNSSSSGSSGAGQKREDVSAGEDCGPLPEGG
PEPRSDGAKPGPREGKRSYSMEHFRWGKPVGKKRRPVKVYPNGAEDESAEAFPLEFKREL
TGQRLREGDGPDGPADDGAGAQADLEHSLLVAAEKKDEGPYRMEHFRWGSPPKDKRYGGF
MTSEKSQTPLVTLFKNAIIKNAYKKGE
Target 4 Number of Residues 271
Target 4 Molecular Weight 29424
Target 4 Theoretical pI 7.75
Target 4 GO Classification
Function
signal transducer activity
receptor binding
hormone activity
Process
Not Available
Component
extracellular region
Target 4 General Function Involved in hormone activity
Target 4 Specific Function Beta-endorphin and Met-enkephalin are endogenous opiates
Target 4 Pathways Not Available
Target 4 Reactions Not Available
Target 4 Pfam Domain Function
Target 4 Signals
  • 1-26
Target 4 Transmembrane Regions
  • None
Target 4 Essentiality Non-Essential
Target 4 GenBank ID Protein 190188 Link Image
Target 4 UniProtKB/Swiss-Prot ID P01189 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name COLI_HUMAN Link Image
Target 4 PDB ID Not Available
Target 4 Cellular Location Not Available
Target 4 Gene Sequence >789 bp 
TGCAGCCGCTCGGGGGCCCTGTTGCTGGCCTTGCTGCTTCAGGCCTCCATGGAAGTGCGT
GGCTGGTGCCTGGAGAGCAGCCAGTGTCAGGACCTCACCACGGAAAGCAACCTGCTGGAG
TGCATCCGGGCCTGCAAGCCCGACCTCTCGGCCGAGACTCCCATGTTCCCGGGAAATGGC
GACGAGCAGCCTCTGACCGAGAACCCCCGGAAGTACGTCATGGGCCACTTCCGCTGGGAC
CGATTCGGCCGCCGCAACAGCAGCAGCAGCGGCAGCAGCGGCGCAGGGCAGAAGCGCGAG
GACGTCTCAGCGGGCGAAGACTGCGGCCCGCTGCCTGAGGGCGGCCCCGAGCCCCGCAGC
GATGGTGCCAAGCCGGGCCCGCGCGAGGGCAAGCGCTCCTACTCCATGGAGCACTTCCGC
TGGGGCAAGCCGGTGGGCAAGAAGCGGCGCCCAGTGAAGGTGTACCCTAACGGCGCCGAG
GACGAGTCGGCCGAGGCCTTCCCCCTGGAGTTCAAGAGGGAGCTGACTGGCCAGCGACTC
CGGGAGGGAGATGGCCCCGACGGCCCTGCCGATGACGGCGCAGGGGCCCAGGCCGACCTG
GAGCACAGCCTGCTGGTGGCGGCCGAGAAGAAGGACGAGGGCCCCTACAGGATGGAGCAC
TTCCGCTGGGGCAGCCCGCCCAAGGACAAGCGCTACGGCGGTTTCATGACCTCCGAGAAG
AGCCAGACGCCCCTGGTGACGCTGTTCAAAAACGCCATCATCAAGAACGCCTACAAGAAG
GGCGAGTGA
Target 4 GenBank Gene ID
Target 4 GeneCard ID POMC Link Image
Target 4 GenAtlas ID POMC Link Image
Target 4 HGNC ID HGNC:9201 Link Image
Target 4 Chromosome Location 2
Target 4 Locus 2p23.3
Target 4 SNPs SNPJam Report Link Image
Target 4 General References
  1. Echwald SM, Sorensen TI, Andersen T, Tybjaerg-Hansen A, Clausen JO, Pedersen O: Mutational analysis of the proopiomelanocortin gene in Caucasians with early onset obesity. Int J Obes Relat Metab Disord. 1999 Mar;23(3):293-8. [PubMed Link Image]
  2. Miraglia del Giudice E, Cirillo G, Santoro N, D'Urso L, Carbone MT, Di Toro R, Perrone L: Molecular screening of the proopiomelanocortin (POMC ) gene in Italian obese children: report of three new mutations. Int J Obes Relat Metab Disord. 2001 Jan;25(1):61-7. [PubMed Link Image]
  3. Li CH, Chung D: Primary structure of human beta-lipotropin. Nature. 1976 Apr 15;260(5552):622-4. [PubMed Link Image]
  4. Dragon N, Seidah NG, Lis M, Routhier R, Chretien M: Primary structure and morphine-like activity of human beta-endorphin. Can J Biochem. 1977 Jun;55(6):666-70. [PubMed Link Image]
  5. Bovenberg RA, Burbach JP, Wiegant VM, Veeneman GH, van Boom JH, Baas PD, Jansz HS, de Wied D: gamma-Endorphin and schizophrenia: amino acid composition of gamma-endorphin and nucleotide sequence of gamma-endorphin cDNA from pituitary glands of schizophrenic patients. Brain Res. 1986 Jun 18;376(1):29-37. [PubMed Link Image]
  6. Fenger M, Johnsen AH: Alpha-amidated peptides derived from pro-opiomelanocortin in normal human pituitary. Biochem J. 1988 Mar 15;250(3):781-8. [PubMed Link Image]
  7. Golovin SIa, Karginov VA, Bondar' AA, Beklemishev AB, Chekhranova MK: [Synthesis, cloning and primary structure of DNA complementary to mRNA for human pituitary pro-opiomelanocortin] Bioorg Khim. 1987 Apr;13(4):562-4. [PubMed Link Image]
  8. Riniker B, Sieber P, Rittel W, Zuber H: Revised amino-acid sequences for porcine and human adrenocorticotrophic hormone. Nat New Biol. 1972 Jan 26;235(56):114-5. [PubMed Link Image]
  9. Sieber P, Rittel W, Riniker B: [Synthesis of the human adrenal cortex hormone ( h ACTH) with a revised amino acid sequence] Helv Chim Acta. 1972;55(4):1243-66. [PubMed Link Image]
  10. Yamashiro D, Li CH: Adrenocorticotropins. 44. Total synthesis of the human hormone by the solid-phase method. J Am Chem Soc. 1973 Feb 21;95(4):1310-5. [PubMed Link Image]
  11. 4352834 Bennett HP, Lowry PJ, McMartin C: Confirmation of the 1-20 amino acid sequence of human adrenocorticotrophin. Biochem J. 1973 May;133(1):11-3.
  12. 6254047 Chang AC, Cochet M, Cohen SN: Structural organization of human genomic DNA encoding the pro-opiomelanocortin peptide. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4890-4.
  13. 6267033 Seidah NG, Rochemont J, Hamelin J, Lis M, Chretien M: Primary structure of the major human pituitary pro-opiomelanocortin NH2-terminal glycopeptide. Evidence for an aldosterone-stimulating activity. J Biol Chem. 1981 Aug 10;256(15):7977-84.
  14. 6272808 Seidah NG, Rochemont J, Hamelin J, Benjannet S, Chretien M: The missing fragment of the pro-sequence of human pro-opiomelanocortin: sequence and evidence for C-terminal amidation. Biochem Biophys Res Commun. 1981 Sep 30;102(2):710-6.
  15. 6274691 Takahashi H, Teranishi Y, Nakanishi S, Numa S: Isolation and structural organization of the human corticotropin--beta-lipotropin precursor gene. FEBS Lett. 1981 Nov 30;135(1):97-102.
  16. 6299668 Whitfeld PL, Seeburg PH, Shine J: The human pro-opiomelanocortin gene: organization, sequence, and interspersion with repetitive DNA. DNA. 1982;1(2):133-43.
  17. 6314261 Takahashi H, Hakamata Y, Watanabe Y, Kikuno R, Miyata T, Numa S: Complete nucleotide sequence of the human corticotropin-beta-lipotropin precursor gene. Nucleic Acids Res. 1983 Oct 11;11(19):6847-58.
  18. 6945581 Seidah NG, Chretien M: Complete amino acid sequence of a human pituitary glycopeptide: an important maturation product of pro-opiomelanocortin. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4236-40.
  19. 7828531 Morris JC, Savva D, Lowry PJ: Reduced expression of a naturally deleted form of human proopiomelanocortin complementary deoxyribonucleic acid after transfection into Chinese hamster ovary cells. Endocrinology. 1995 Jan;136(1):195-201.
  20. 9768693 Hinney A, Becker I, Heibult O, Nottebom K, Schmidt A, Ziegler A, Mayer H, Siegfried W, Blum WF, Remschmidt H, Hebebrand J: Systematic mutation screening of the pro-opiomelanocortin gene: identification of several genetic variants including three different insertions, one nonsense and two missense point mutations in probands of different weight extremes. J Clin Endocrinol Metab. 1998 Oct;83(10):3737-41.
Target 4 Drug References
  1. Vinson GP, Laird SM, Hinson JP, Teja R: Origin of aldosterone in trypsin-stimulated rat adrenal zona glomerulosa incubations. J Endocrinol. 1992 Oct;135(1):125-33. [PubMed Link Image]
  2. Cerundolo R, Lloyd DH, Persechino A, Evans H, Cauvin A: Treatment of canine Alopecia X with trilostane. Vet Dermatol. 2004 Oct;15(5):285-93. [PubMed Link Image]
  3. Leone F, Cerundolo R, Vercelli A, Lloyd DH: The use of trilostane for the treatment of alopecia X in Alaskan malamutes. J Am Anim Hosp Assoc. 2005 Sep-Oct;41(5):336-42. [PubMed Link Image]
  4. Kawai K, Baba K, Senba M, Nakamura T, Doi Y, Yamaguchi T, Hashiba K, Tsuchiyama H: Effect of the adrenal inhibitor trilostane on the morphology of the adrenocortical cells of Dahl salt-sensitive and Dahl salt-resistant rats. Int J Exp Pathol. 1991 Aug;72(4):451-62. [PubMed Link Image]
  5. Bell R, Neiger R, McGrotty Y, Ramsey IK: Study of the effects of once daily doses of trilostane on cortisol concentrations and responsiveness to adrenocorticotrophic hormone in hyperadrenocorticoid dogs. Vet Rec. 2006 Aug 26;159(9):277-81. [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.