Identification

Name
Corticotropin
Accession Number
DB01285  (DB09547)
Type
Biotech
Groups
Approved, Investigational, Vet approved
Biologic Classification
Protein Based Therapies
Hormones
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.

Protein chemical formula
C207H308N56O58S
Protein average weight
4541.0658 Da
Sequences
>ACTH(1-39)
SYSMEHFRWGKPVGKKRRPVKVYPDGAEDQLAEAFPLEF
Download FASTA Format
Synonyms
  • ACTH
  • Adrenocorticotrophin
  • Adrenocorticotropic hormone
  • Corticotrophin
  • Cortigel
  • H.P. acthar gel
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Acthar Gel Hp Inj 40unit/mlGel40 unitIntramuscular; SubcutaneousArmour Pharmaceutical Co.1987-12-311999-12-15Canada
Acthar Powder Inj 40unit/vialPowder, for solution40 unitIntramuscular; Intravenous; SubcutaneousArmour Pharmaceutical Co.1988-12-311999-12-15Canada
H.P. ActharInjection80 [USP'U]/1mLIntramuscular; SubcutaneousQuestcor Pharmaceuticals, Inc.2010-10-152013-08-31Us
H.P. ActharInjection80 [iU]/1mLIntravenousCangene Biopharma2005-09-092010-02-24Us
H.P. ActharInjection80 [USP'U]/1mLIntramuscular; SubcutaneousMallinckrodt Ard Inc.2013-01-07Not applicableUs
International/Other Brands
Acthar / Acthar Gel
Categories
UNII
K0U68Q2TXA
CAS number
12427-33-7

Pharmacology

Indication

For use as a diagnostic agent in the screening of patients presumed to have adrenocortical insufficiency.

Associated Conditions
Pharmacodynamics

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.

TargetActionsOrganism
AAdrenocorticotropic hormone receptor
agonist
Human
UCorticoliberin
agonist
Human
Absorption

Corticotropin is rapidly absorbed following intramuscular administration; the repository dosage form is slowly absorbed over approximately 8 to 16 hours.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

About 15 minutes following intravenous administration.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(1S,6R)-3-{[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]CARBONYL}-6-(2,4,5-TRIFLUOROPHENYL)CYCLOHEX-3-EN-1-AMINEThe therapeutic efficacy of (1S,6R)-3-{[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]CARBONYL}-6-(2,4,5-TRIFLUOROPHENYL)CYCLOHEX-3-EN-1-AMINE can be decreased when used in combination with Corticotropin.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Corticotropin.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Corticotropin.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Corticotropin.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Corticotropin.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Corticotropin.
AICA ribonucleotideThe therapeutic efficacy of AICA ribonucleotide can be decreased when used in combination with Corticotropin.
AlclometasoneThe risk or severity of adverse effects can be increased when Corticotropin is combined with Alclometasone.
AldesleukinThe risk or severity of adverse effects can be increased when Corticotropin is combined with Aldesleukin.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Corticotropin.
Food Interactions
Not Available

References

Synthesis Reference

Wylie W. Vale, Jr., Mary P. Stenzel-Poore, "Corticotropin-releasing factor overproducing transgenic mice." U.S. Patent US6023011, issued June, 1993.

US6023011
General References
Not Available
External Links
KEGG Drug
D00146
KEGG Compound
C02017
PubChem Substance
46506307
ChEMBL
CHEMBL1201610
PharmGKB
PA449129
Drugs.com
Drugs.com Drug Page
Wikipedia
Adrenocorticotropic_hormone
ATC Codes
H01AA01 — Corticotropin
MSDS
Download (72.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOptic Neuritis1
1CompletedSupportive CareAdrenal Cortex Diseases / Infant Morbidity1
1CompletedTreatmentDisseminated Sclerosis1
1CompletedTreatmentIdiopathic Membranous Nephropathy1
1TerminatedTreatmentEnd Stage Renal Disease (ESRD)1
2CompletedTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2CompletedTreatmentChronic Migraine1
2CompletedTreatmentDermatomyositis / Polymyositis1
2CompletedTreatmentDiabetic Nephropathies1
2CompletedTreatmentEpilepsies / Infantile Spasms (IS)1
2Not Yet RecruitingTreatmentScleritis1
2Not Yet RecruitingTreatmentUveitis1
2RecruitingTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2RecruitingTreatmentMultiple Sclerosis, Primary Progressive / Progressive Relapsing Multiple Sclerosis / Secondary Progressive Multiple Sclerosis (SPMS)1
2RecruitingTreatmentRheumatoid Arthritis1
2TerminatedTreatmentDisseminated Sclerosis1
2WithdrawnTreatmentAcute Respiratory Distress Syndrome (ARDS)1
2WithdrawnTreatmentChronic Inflammatory Demyelinating Polyneuropathy (CIDP)1
2, 3TerminatedTreatmentDisseminated Sclerosis1
2, 3Unknown StatusTreatmentHypercalcemia Due to Sarcoidosis / Sarcoidosis1
3Active Not RecruitingTreatmentGlomerulonephritis minimal lesion1
3Active Not RecruitingTreatmentProgressive IgA Nephropathy / Proteinuria1
3Active Not RecruitingTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
3CompletedDiagnosticDevelopment1
3CompletedTreatmentDisseminated Neuroblastoma / Localized Resectable Neuroblastoma / Localized Unresectable Neuroblastoma / Regional Neuroblastoma / Stage 4S Neuroblastoma1
3Enrolling by InvitationSupportive CareDisseminated Sclerosis1
3Not Yet RecruitingTreatmentRheumatoid Arthritis1
3RecruitingPreventionFSGS1
4Active Not RecruitingTreatmentRheumatoid Arthritis1
4Active Not RecruitingTreatmentSystemic Lupus Erythematosus (SLE)1
4Active Not RecruitingTreatmentDiffuse posterior uveitis / Vasculitis Retinal1
4CompletedDiagnosticInfantile Spasms (IS)1
4CompletedTreatmentAnterior Uveitis (AU) / Clinically Significant Macular Edema / Diffuse posterior uveitis / Scleritis / Uveitis / Uveitis, Intermediate1
4CompletedTreatmentDiabetic Nephropathies / Glomerulonephritis minimal lesion1
4CompletedTreatmentDisseminated Sclerosis1
4CompletedTreatmentGlomerulonephritis minimal lesion1
4CompletedTreatmentIdiopathic Membranous Nephropathy / Proteinuria1
4CompletedTreatmentKidney Diseases1
4CompletedTreatmentLupus Erythematosus Systemic Exacerbation1
4CompletedTreatmentRheumatoid Arthritis2
4CompletedTreatmentTreatment Resistant Nephrotic Syndrome1
4Not Yet RecruitingDiagnosticSteroid-Resistant Nephrotic Syndrome1
4Not Yet RecruitingTreatmentDisseminated Sclerosis1
4Not Yet RecruitingTreatmentDry Eye Syndrome (DES)1
4Not Yet RecruitingTreatmentFSGS / Transplantation, Kidney / Transplantation, Renal1
4Not Yet RecruitingTreatmentKeratoconjunctivitis Sicca1
4Not Yet RecruitingTreatmentDiffuse posterior uveitis / Panuveitis / Uveitis, Intermediate1
4Not Yet RecruitingTreatmentSarcoidosis2
4RecruitingDiagnosticRheumatoid Arthritis1
4RecruitingTreatmentCNS Sarcoidosis1
4RecruitingTreatmentDermatomyositis / Juvenile Dermatomyositis1
4RecruitingTreatmentDisseminated Sclerosis1
4RecruitingTreatmentGlomerulonephritis membranous1
4RecruitingTreatmentIdiopathic Focal Segmental Glomerulosclerosis1
4RecruitingTreatmentLupus Erythematosus, Systemic1
4RecruitingTreatmentNephritis, Lupus1
4RecruitingTreatmentPsoriatic Arthritis1
4RecruitingTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
4RecruitingTreatmentRepository Corticotropin Injection / Systemic Lupus Erythematosus (SLE)1
4RecruitingTreatmentRheumatoid Arthritis1
4RecruitingTreatmentSarcoidosis, Pulmonary1
4RecruitingTreatmentSarcoidosis / Sarcoidosis, Pulmonary1
4RecruitingTreatmentUveitis1
4TerminatedTreatmentDisseminated Sclerosis1
4Unknown StatusTreatmentDisseminated Sclerosis1
4Unknown StatusTreatmentProteinuria / Transplant Glomerulopathy1
4Unknown StatusTreatmentPsoriatic Arthritis1
4WithdrawnTreatmentIgA Nephropathy / Proteinuria1
4WithdrawnTreatmentSLE Glomerulonephritis Syndrome, WHO Class V1
Not AvailableActive Not RecruitingNot AvailableGlomerulonephritis minimal lesion1
Not AvailableActive Not RecruitingOtherAutonomic Nervous System / Baroreflexes / Stress, Physiological1
Not AvailableCompletedDiagnosticAdrenal Insufficiency / Chronic Lymphocytic Thyroiditis1
Not AvailableCompletedDiagnosticShock, Septic1
Not AvailableCompletedOtherRelapsing Remitting Multiple Sclerosis (RRMS)1
Not AvailableCompletedScreeningOther Diseases or Conditions1
Not AvailableCompletedScreeningPolycystic Ovaries Syndrome1
Not AvailableEnrolling by InvitationNot AvailableDermatomyositis / Polymyositis1
Not AvailableNot Yet RecruitingNot AvailableSarcoid Uveitis1
Not AvailableRecruitingNot AvailableDecrease of Proteinuria With H.P. Acthar Gel and Its Effects on Clinical and Podocyte Function1
Not AvailableRecruitingNot AvailableRelapsing Remitting Multiple Sclerosis (RRMS)1
Not AvailableRecruitingBasic ScienceBMI >30 kg/m2 / Hyperandrogenemia / Polycystic Ovaries Syndrome1
Not AvailableRecruitingTreatmentAnterior Uveitis (AU) / Ocular Sarcoidosis / Panuveitis1
Not AvailableRecruitingTreatmentDisseminated Sclerosis1
Not AvailableRecruitingTreatmentProteinuria1
Not AvailableRecruitingTreatmentRheumatoid Arthritis1
Not AvailableRecruitingTreatmentTransplant Glomerulopathy1
Not AvailableUnknown StatusPreventionWest Syndrome1
Not AvailableUnknown StatusTreatmentDisseminated Sclerosis1
Not AvailableUnknown StatusTreatmentRheumatoid Arthritis1
Not AvailableWithdrawnTreatmentKidney Diseases1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Biovectra Inc.
  • Questcor
Dosage forms
FormRouteStrength
GelIntramuscular; Subcutaneous40 unit
Powder, for solutionIntramuscular; Intravenous; Subcutaneous40 unit
InjectionIntramuscular; Subcutaneous80 [USP'U]/1mL
InjectionIntravenous80 [iU]/1mL
Prices
Unit descriptionCostUnit
Acthar hp gel 80 unit/ml vial5584.56USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityEasily soluble in cold water, hot water.Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Melanocortin receptor activity
Specific Function
Receptor for corticotropin (ACTH). This receptor is mediated by G proteins (G(s)) which activate adenylate cyclase (cAMP).
Gene Name
MC2R
Uniprot ID
Q01718
Uniprot Name
Adrenocorticotropic hormone receptor
Molecular Weight
33926.28 Da
References
  1. 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:17636172]
  2. 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:16478774]
  3. 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:17584128]
  4. 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:17185906]
  5. 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:17223989]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Receptor binding
Specific Function
Hormone regulating the release of corticotropin from pituitary gland (By similarity). Induces NLRP6 in intestinal epithelial cells, hence may influence gut microbiota profile (By similarity).
Gene Name
CRH
Uniprot ID
P06850
Uniprot Name
Corticoliberin
Molecular Weight
21421.505 Da
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:16467980]
  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:16472586]
  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:16503922]
  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:16523405]
  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:16534240]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid delta-isomerase activity
Specific Function
3-beta-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 3-beta-HSD enzymatic system pl...
Gene Name
HSD3B2
Uniprot ID
P26439
Uniprot Name
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2
Molecular Weight
42051.845 Da
References
  1. Bassett MH, Suzuki T, Sasano H, De Vries CJ, Jimenez PT, Carr BR, Rainey WE: The orphan nuclear receptor NGFIB regulates transcription of 3beta-hydroxysteroid dehydrogenase. implications for the control of adrenal functional zonation. J Biol Chem. 2004 Sep 3;279(36):37622-30. Epub 2004 Jun 18. [PubMed:15208301]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Iron ion binding
Specific Function
Catalyzes the conversion of 25-hydroxyvitamin D3 (25(OH)D) to 1-alpha,25-dihydroxyvitamin D3 (1,25(OH)2D) plays an important role in normal bone growth, calcium metabolism, and tissue differentiation.
Gene Name
CYP27B1
Uniprot ID
O15528
Uniprot Name
25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial
Molecular Weight
56503.475 Da
References
  1. Dunbar DR, Khaled H, Evans LC, Al-Dujaili EA, Mullins LJ, Mullins JJ, Kenyon CJ, Bailey MA: Transcriptional and physiological responses to chronic ACTH treatment by the mouse kidney. Physiol Genomics. 2010 Feb 4;40(3):158-66. doi: 10.1152/physiolgenomics.00088.2009. Epub 2009 Nov 17. [PubMed:19920212]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxidoreductase activity
Specific Function
Has a role in maintaining calcium homeostasis. Catalyzes the NADPH-dependent 24-hydroxylation of calcidiol (25-hydroxyvitamin D(3)) and calcitriol (1-alpha,25-dihydroxyvitamin D(3)). The enzyme can...
Gene Name
CYP24A1
Uniprot ID
Q07973
Uniprot Name
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial
Molecular Weight
58874.695 Da
References
  1. Dunbar DR, Khaled H, Evans LC, Al-Dujaili EA, Mullins LJ, Mullins JJ, Kenyon CJ, Bailey MA: Transcriptional and physiological responses to chronic ACTH treatment by the mouse kidney. Physiol Genomics. 2010 Feb 4;40(3):158-66. doi: 10.1152/physiolgenomics.00088.2009. Epub 2009 Nov 17. [PubMed:19920212]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Hanafusa J, Mune T, Tanahashi T, Isomura Y, Suwa T, Isaji M, Daido H, Morita H, Murayama M, Yasuda K: Altered corticosteroid metabolism differentially affects pituitary corticotropin response. Am J Physiol Endocrinol Metab. 2002 Feb;282(2):E466-73. doi: 10.1152/ajpendo.00065.2001. [PubMed:11788380]
  2. Dimaraki EV, Jaffe CA: Troglitazone induces CYP3A4 activity leading to falsely abnormal dexamethasone suppression test. J Clin Endocrinol Metab. 2003 Jul;88(7):3113-6. doi: 10.1210/jc.2002-021778. [PubMed:12843151]

Drug created on May 23, 2007 23:14 / Updated on August 02, 2018 04:34