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Showing drug card for Corticotropin (DB01285)

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Version 2.5
Creation Date 2007-05-24 05:14:31
Update Date 2009-02-19 16:03:36
Primary Accession Number DB01285
Secondary Accession Number Not Available
Name Corticotropin
Drug Type
  • Approved
  • Biotech
Description Corticotropin (ACTH or adrenocorticotropic hormone) is a polypeptide hormone produced and secreted by the pituitary gland. It is an important player in the hypothalamic-pituitary-adrenal axis.
Synonyms
  1. ACTH
  2. Adrenocorticotopin
  3. Adrenocorticotropic hormone
  4. Corticotrophin
  5. Cortrophin
Brand Names
  1. ACTH
  2. Acethropan
  3. Acortan
  4. Acthar
  5. Exacthin
  6. H.P. Acthar Gel
  7. Isactid
  8. Purified cortrophin gel
  9. Reacthin
  10. Solacthyl
  11. Tubex
Brand Mixtures Not Available
Chemical IUPAC Name Not Available
Chemical Formula C207H308N56O58S
Chemical Structure Structure
Protein Sequence(s) >ACTH(1-39) 
SYSMEHFRWGKPVGKKRRPVKVYPDGAEDQLAEAFPLEF
CAS Registry Number 9002-60-2
InChI Identifier Not Available
InChI Key Not Available
KEGG Drug D00146 Link Image
KEGG Compound C02017 Link Image
PubChem Compound Not Available
PubChem Substance 7847214 Link Image
ChEBI ID Not Available
PharmGKB ID PA449129 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/Adrenocorticotropic_hormone Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 4541.0658
Monoisotopic Molecular Weight 4538.2594
State Solid
Melting Point Not Available
Experimental Water Solubility Easily soluble in cold water, hot water. Source: PhysProp
Predicted Water Solubility Not Available Calculated using ALOGPS
Experimental LogP/Hydrophobicity Not Available Source: PhysProp
Predicted LogP Not Available Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS Not Available Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Not Available
SDF File Not Available
PDB File Not Available
Experimental PDB ID Not Available
Isomeric SMILES Not Available
Canonical SMILES Not Available
Drug Category
  • Diagnostic Agents
ATC Codes
AHFS Codes Not Available
Indication For use as a diagnostic agent in the screening of patients presumed to have adrenocortical insufficiency.
Pharmacology Corticotropin acts through the stimulation of cell surface ACTH receptors, which are primarily located on the adrenocortical cells. Corticotropin stimulates the cortex of the adrenal gland and boosts the synthesis of corticosteroids, mainly glucocorticoids but also sex steroids (androgens). Corticotropin is also related to the circadian rhythm in many organisms.
Mechanism of Action As a diagnostic aid (adrenocortical function), corticotropin combines with a specific receptor on the adrenal cell plasma membrane. In patients with normal adrenocortical function, it stimulates the initial reaction involved in the synthesis of adrenal steroids (including cortisol, cortisone, weak androgenic substances, and a limited quantity of aldosterone) from cholesterol by increasing the quantity of cholesterol within the mitochondria. Corticotropin does not significantly increase serum cortisol concentrations in patients with primary adrenocortical insufficiency (Addison's disease). The mechanism of action of corticotropin in the treatment of infantile myoclonic seizures is unknown.
Absorption Corticotropin is rapidly absorbed following intramuscular administration; the repository dosage form is slowly absorbed over approximately 8 to 16 hours.
Toxicity Not Available
Protein Binding Not Available
Biotransformation Not Available
Half Life About 15 minutes following intravenous administration.
Dosage Forms Not Available
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. Wikipedia Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Adrenocorticotropic hormone receptor
  2. Corticoliberin
Drug Target 1 [top]
Target 1 ID 945
Target 1 Name Adrenocorticotropic hormone receptor
Target 1 Synonyms
  1. ACTH receptor
  2. ACTH-R
  3. Adrenocorticotropin receptor
  4. MC2-R
  5. Melanocortin receptor 2
Target 1 Gene Name MC2R
Target 1 Protein Sequence >Adrenocorticotropic hormone receptor 
MKHIINSYENINNTARNNSDCPRVVLPEEIFFTISIVGVLENLIVLLAVFKNKNLQAPMY
FFICSLAISDMLGSLYKILENILIILRNMGYLKPRGSFETTADDIIDSLFVLSLLGSIFS
LSVIAADRYITIFHALRYHSIVTMRRTVVVLTVIWTFCTGTGITMVIFSHHVPTVITFTS
LFPLMLVFILCLYVHMFLLARSHTRKISTLPRANMKGAITLTILLGVFIFCWAPFVLHVL
LMTFCPSNPYCACYMSLFQVNGMLIMCNAVIDPFIYAFRSPELRDAFKKMIFCSRYW
Target 1 Number of Residues 301
Target 1 Molecular Weight 33927
Target 1 Theoretical pI 8.82
Target 1 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
peptide receptor activity, G-protein coupled
melanocortin receptor activity
adrenocorticotropin receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Involved in adrenocorticotropin receptor activity
Target 1 Specific Function Receptor for ACTH. This receptor is mediated by G proteins (G(s)) which activate adenylate cyclase
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 24-49
  • 59-79
  • 105-126
  • 148-168
  • 181-199
  • 218-244
  • 257-278
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 28344 Link Image
Target 1 UniProtKB/Swiss-Prot ID Q01718 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name ACTHR_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >894 bp 
ATGAAGCACATTATCAACTCGTATGAAAACATCAACAACACAGCAAGAAATAATTCCGAC
TGTCCTCGTGTGGTTTTGCCGGAGGAGATATTTTTCACAATTTCCATTGTTGGAGTTTTG
GAGAATCTGATCGTCCTGCTGGCTGTGTTCAAGAATAAGAATCTCCAGGCACCCATGTAC
TTTTTCATCTGTAGCTTGGCCATATCTGATATGCTGGGCAGCCTATATAAGATCTTGGAA
AATATCCTGATCATATTGAGAAACATGGGCTATCTCAAGCCACGTGGCAGTTTTGAAACC
ACAGCCGATGACATCATCGACTCCCTGTTTGTCCTCTCCCTGCTTGGCTCCATCTTCAGC
CTGTCTGTGATTGCTGCGGACCGCTACATCACCATCTTCCACGCACTGCGGTACCACAGC
ATCGTGACCATGCGCCGCACTGTGGTGGTGCTTACGGTCATCTGGACGTTCTGCACGGGG
ACTGGCATCACCATGGTGATCTTCTCCCATCATGTGCCCACAGTGATCACCTTCACGTCG
CTGTTCCCGCTGATGCTGGTCTTCATCCTGTGCCTCTATGTGCACATGTTCCTGCTGGCT
CGATCCCACACCAGGAAGATCTCCACCCTCCCCAGAGCCAACATGAAAGGGGCCATCACA
CTGACCATCCTGCTCGGGGTCTTCATCTTCTGCTGGGCCCCCTTTGTGCTTCATGTCCTC
TTGATGACATTCTGCCCAAGTAACCCCTACTGCGCCTGCTACATGTCTCTCTTCCAGGTG
AACGGCATGTTGATCATGTGCAATGCCGTCATTGACCCCTTCATATATGCCTTCCGGAGC
CCAGAGCTCAGGGACGCATTCAAAAAGATGATCTTCTGCAGCAGGTACTGGTAG
Target 1 GenBank Gene ID
Target 1 GeneCard ID MC2R Link Image
Target 1 GenAtlas ID MC2R Link Image
Target 1 HGNC ID HGNC:6930 Link Image
Target 1 Chromosome Location 18
Target 1 Locus 18p11.2
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Ishii T, Ogata T, Sasaki G, Sato S, Kinoshita EI, Matsuo N: Novel mutations of the ACTH receptor gene in a female adult patient with adrenal unresponsiveness to ACTH. Clin Endocrinol (Oxf). 2000 Sep;53(3):389-92. [PubMed Link Image]
  2. Fluck CE, Martens JW, Conte FA, Miller WL: Clinical, genetic, and functional characterization of adrenocorticotropin receptor mutations using a novel receptor assay. J Clin Endocrinol Metab. 2002 Sep;87(9):4318-23. [PubMed Link Image]
  3. Mountjoy KG, Robbins LS, Mortrud MT, Cone RD: The cloning of a family of genes that encode the melanocortin receptors. Science. 1992 Aug 28;257(5074):1248-51. [PubMed Link Image]
  4. Clark AJ, McLoughlin L, Grossman A: Familial glucocorticoid deficiency associated with point mutation in the adrenocorticotropin receptor. Lancet. 1993 Feb 20;341(8843):461-2. [PubMed Link Image]
  5. Tsigos C, Arai K, Hung W, Chrousos GP: Hereditary isolated glucocorticoid deficiency is associated with abnormalities of the adrenocorticotropin receptor gene. J Clin Invest. 1993 Nov;92(5):2458-61. [PubMed Link Image]
  6. Gantz I, Konda Y, Tashiro T, Shimoto Y, Miwa H, Munzert G, Watson SJ, DelValle J, Yamada T: Molecular cloning of a novel melanocortin receptor. J Biol Chem. 1993 Apr 15;268(11):8246-50. [PubMed Link Image]
  7. Naville D, Barjhoux L, Jaillard C, Faury D, Despert F, Esteva B, Durand P, Saez JM, Begeot M: Demonstration by transfection studies that mutations in the adrenocorticotropin receptor gene are one cause of the hereditary syndrome of glucocorticoid deficiency. J Clin Endocrinol Metab. 1996 Apr;81(4):1442-8. [PubMed Link Image]
Target 1 Drug References
  1. Carey LC, Su Y, Valego NK, Rose JC: Infusion of ACTH stimulates expression of adrenal ACTH receptor and steroidogenic acute regulatory protein mRNA in fetal sheep. Am J Physiol Endocrinol Metab. 2006 Aug;291(2):E214-20. Epub 2006 Feb 14. [PubMed Link Image]
  2. Suri D, Alonso M, Weiss RE: A case of ACTH-independent bilateral macronodular adrenal hyperplasia and severe congestive heart failure. J Endocrinol Invest. 2006 Nov;29(10):940-6. [PubMed Link Image]
  3. Lin L, Hindmarsh PC, Metherell LA, Alzyoud M, Al-Ali M, Brain CE, Clark AJ, Dattani MT, Achermann JC: Severe loss-of-function mutations in the adrenocorticotropin receptor (ACTHR, MC2R) can be found in patients diagnosed with salt-losing adrenal hypoplasia. Clin Endocrinol (Oxf). 2007 Feb;66(2):205-10. [PubMed Link Image]
  4. Hruby VJ, Cai M, Cain JP, Mayorov AV, Dedek MM, Trivedi D: Design, synthesis and biological evaluation of ligands selective for the melanocortin-3 receptor. Curr Top Med Chem. 2007;7(11):1107-19. [PubMed Link Image]
  5. Johnston H, King PJ, O'Shaughnessy PJ: Effects of ACTH and expression of the melanocortin-2 receptor in the neonatal mouse testis. Reproduction. 2007 Jun;133(6):1181-7. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 1566
Target 2 Name Corticoliberin
Target 2 Synonyms
  1. CRF
  2. Corticoliberin precursor
  3. Corticotropin-releasing factor
  4. Corticotropin-releasing hormone
Target 2 Gene Name CRH
Target 2 Protein Sequence >Corticoliberin precursor 
MRLPLLVSAGVLLVALLPCPPCRALLSRGPVPGARQAPQHPQPLDFFQPPPQSEQPQQPQ
ARPVLLRMGEEYFLRLGNLNKSPAAPLSPASSLLAGGSGSRPSPEQATANFFRVLLQQLL
LPRRSLDSPAALAERGARNALGGHQEAPERERRSEEPPISLDLTFHLLREVLEMARAEQL
AQQAHSNRKLMEIIGK
Target 2 Number of Residues 199
Target 2 Molecular Weight 21422
Target 2 Theoretical pI 10.55
Target 2 GO Classification
Function
signal transducer activity
receptor binding
hormone activity
Process
Not Available
Component
extracellular region
Target 2 General Function Involved in hormone activity
Target 2 Specific Function This hormone from hypothalamus regulates the release of corticotropin from pituitary gland
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • 1-24
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 35356 Link Image
Target 2 UniProtKB/Swiss-Prot ID P06850 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name CRF_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Secreted protein
Target 2 Gene Sequence >591 bp 
ATGCGGCTGCCGCTGCTTGTGTCCGCGGGAGTCCTGCTGGTGGCTCTCCTGCCCTGCCCG
CCATGCAGGGCGCTCCTGAGCCGCGGGCCGGTCCCGGGAGCTCGGCAGGCGCCGCAGCAC
CCTCAGCCCTTGGATTTCTTCCAGCCGCCGCCGCAGTCCGAGCAGCCCCAGCAGCCGCAG
GCTCGGCCGGTCCTGCTCCGCATGGGAGAGGAGTACTTCCTCCGCCTGGGGAACCTCAAC
AAGAGCCCGGCCGCTCCCCTTTCGCCCGCCTCCTCGCTCCTCGCCGGAGGCAGCGGCAGC
CGCCCTTCGCCGGAACAGGCGACCGCCAACTTTTTCCGCGTGTTGCTGCAGCAGCTGCTG
CTGCCTCGGCGCTCGCTCGACAGCCCCGCGGCTCTCGCGGAGCGCGGCGCTAGGAATGCC
CTCGGCGGCCACCAGGAGGCACCGGAGAGAGAAAGGCGGTCCGAGGAGCCTCCCATCTCC
CTGGATCTCACCTTCCACCTCCTCCGGGAAGTCTTGGAAATGGCCAGGGCCGAGCAGTTA
GCACAGCAAGCTCACAGCAACAGGAAACTCATGGAGATTATTGGGAAATAA
Target 2 GenBank Gene ID
Target 2 GeneCard ID CRH Link Image
Target 2 GenAtlas ID CRH Link Image
Target 2 HGNC ID HGNC:2355 Link Image
Target 2 Chromosome Location 8
Target 2 Locus 8q13
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Robinson BG, D'Angio LA Jr, Pasieka KB, Majzoub JA: Preprocorticotropin releasing hormone: cDNA sequence and in vitro processing. Mol Cell Endocrinol. 1989 Feb;61(2):175-80. [PubMed Link Image]
  2. Sasaki A, Tempst P, Liotta AS, Margioris AN, Hood LE, Kent SB, Sato S, Shinkawa O, Yoshinaga K, Krieger DT: Isolation and characterization of a corticotropin-releasing hormone-like peptide from human placenta. J Clin Endocrinol Metab. 1988 Oct;67(4):768-73. [PubMed Link Image]
  3. Shibahara S, Morimoto Y, Furutani Y, Notake M, Takahashi H, Shimizu S, Horikawa S, Numa S: Isolation and sequence analysis of the human corticotropin-releasing factor precursor gene. EMBO J. 1983;2(5):775-9. [PubMed Link Image]
  4. Romier C, Bernassau JM, Cambillau C, Darbon H: Solution structure of human corticotropin releasing factor by 1H NMR and distance geometry with restrained molecular dynamics. Protein Eng. 1993 Feb;6(2):149-56. [PubMed Link Image]
Target 2 Drug References
  1. Hellman P, Linder F, Hennings J, Hessman O, Eriksson B, Orlefors H, Akerstrom G: Bilateral adrenalectomy for ectopic Cushing's syndrome-discussions on technique and indication. World J Surg. 2006 May;30(5):909-16. [PubMed Link Image]
  2. Dinan TG, Quigley EM, Ahmed SM, Scully P, O'Brien S, O'Mahony L, O'Mahony S, Shanahan F, Keeling PW: Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker? Gastroenterology. 2006 Feb;130(2):304-11. [PubMed Link Image]
  3. Zhao LF, Iwasaki Y, Oki Y, Tsugita M, Taguchi T, Nishiyama M, Takao T, Kambayashi M, Hashimoto K: Purinergic receptor ligands stimulate pro-opiomelanocortin gene expression in AtT-20 pituitary corticotroph cells. J Neuroendocrinol. 2006 Apr;18(4):273-8. [PubMed Link Image]
  4. Wagner U, Wahle M, Moritz F, Wagner U, Hantzschel H, Baerwald CG: Promoter polymorphisms regulating corticotrophin-releasing hormone transcription in vitro. Horm Metab Res. 2006 Feb;38(2):69-75. [PubMed Link Image]
  5. Matejec R, Uhlich H, Hotz C, Muhling J, Harbach HW, Bodeker RH, Hempelmann G, Teschemacher H: Corticotropin-releasing hormone reduces pressure pain sensitivity in humans without involvement of beta-endorphin(1-31), but does not reduce heat pain sensitivity. Neuroendocrinology. 2005;82(3-4):185-97. Epub 2006 Mar 13. [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.