Tetracosactide

Targets (1)Biointeractions (1)

Identification

Name
Tetracosactide
Accession Number
DB01284
Type
Small Molecule
Groups
Approved
Description

Tetracosactide (also known as Cosyntropin) is a synthetic peptide that is identical to the 24-amino acid segment (sequence: SYSMEHFRWGKPVGKKRRPVKVYP) at the N-terminal of adrenocorticotropic hormone. ACTH (1-24), a segment similar in all species, contains the biological activity that stimulates production of corticosteroids in the adrenal cortex. Tetracosactide exhibits the same activity as natural ACTH with regard to all its biological activities. The complex results in a product whose absorption in man is effected over a longer period of time as compared to corticotropin. Therefore, therapy may be maintained with less frequent administration.

Structure
Thumb
Similar Structures
Synonyms
  • adrenocorticotropic hormone 1-24
  • Adrenocorticotropic hormone fragment 1-24 human, rat
  • alpha(1-24)-corticotrophin
  • ATCH (1-24)
  • beta(1-24)-corticotrophin
  • Corticotropin tetracosapeptide
  • corticotropin-(1-24)
  • corticotropin-(1-24) tetracosapeptide
  • Cosyntropin
  • Tetracosactide
  • Tetracosactrin
  • α1-24-corticotrophin
  • β1-24-corticotrophin
Product Ingredients
IngredientUNIICASInChI Key
Tetracosactide acetateH86HJ92K8Y22633-88-1DFABUZLKSKOWCS-WMPFGLIOSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CortrosynInjection, powder, lyophilized, for solution.25 mg/mLIntramuscular; Intravenous; ParenteralGeneral Injectables & Vaccines2010-03-01Not applicableUs
CortrosynInjection, powder, lyophilized, for solution.25 mg/mLIntramuscular; IntravenousAmphastar Pharmaceuticals, Inc.2003-08-01Not applicableUs
Cortrosyn Inj 0.25mgPowder, for solution0.25 mgIntramuscular; IntravenousAmphastar Pharmaceuticals, Inc.1974-12-31Not applicableCanada
Synacthen DepotSuspension1 mgIntramuscularMallinckrodt Specialty Pharmaceuticals Ireland Ltd.1973-12-31Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CosyntropinInjection, powder, for solution.25 mg/mLIntramuscular; IntravenousMylan Institutional2013-05-08Not applicableUs
CosyntropinInjection, powder, lyophilized, for solution.25 mg/mLIntravenousSandoz2012-06-29Not applicableUs
CosyntropinInjection, powder, for solution.25 mg/mLIntramuscular; IntravenousMylan Institutional2013-05-082018-03-06Us
Categories
UNII
72YY86EA29
CAS number
16960-16-0
Weight
Average: 2933.49
Monoisotopic: 2931.580641316
Chemical Formula
C136H210N40O31S
InChI Key
ZOEFCCMDUURGSE-SQKVDDBVSA-N
InChI
InChI=1S/C136H210N40O31S/c1-75(2)109(127(200)154-71-106(181)156-88(31-13-17-52-137)114(187)158-89(32-14-18-53-138)115(188)159-91(35-21-56-149-134(142)143)116(189)164-96(37-23-58-151-136(146)147)131(204)175-60-25-39-104(175)126(199)173-111(77(5)6)128(201)163-90(33-15-19-54-139)120(193)171-110(76(3)4)129(202)169-101(65-80-43-47-84(180)48-44-80)132(205)176-61-26-40-105(176)133(206)207)172-125(198)103-38-24-59-174(103)130(203)95(34-16-20-55-140)157-107(182)70-153-113(186)99(66-81-68-152-87-30-12-11-29-85(81)87)167-117(190)92(36-22-57-150-135(144)145)160-121(194)98(63-78-27-9-8-10-28-78)166-123(196)100(67-82-69-148-74-155-82)168-118(191)93(49-50-108(183)184)161-119(192)94(51-62-208-7)162-124(197)102(73-178)170-122(195)97(165-112(185)86(141)72-177)64-79-41-45-83(179)46-42-79/h8-12,27-30,41-48,68-69,74-77,86,88-105,109-111,152,177-180H,13-26,31-40,49-67,70-73,137-141H2,1-7H3,(H,148,155)(H,153,186)(H,154,200)(H,156,181)(H,157,182)(H,158,187)(H,159,188)(H,160,194)(H,161,192)(H,162,197)(H,163,201)(H,164,189)(H,165,185)(H,166,196)(H,167,190)(H,168,191)(H,169,202)(H,170,195)(H,171,193)(H,172,198)(H,173,199)(H,183,184)(H,206,207)(H4,142,143,149)(H4,144,145,150)(H4,146,147,151)/t86-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,109-,110-,111-/m0/s1
IUPAC Name
(2S)-1-[(2S)-2-[(2S)-2-[(2S)-6-amino-2-[(2S)-2-{[(2S)-1-[(2S)-2-[(2S)-2-[(2S)-6-amino-2-[(2S)-6-amino-2-{2-[(2S)-2-{[(2S)-1-[(2S)-6-amino-2-{2-[(2S)-2-[(2S)-2-[(2S)-2-[(2S)-2-[(2S)-2-[(2S)-2-[(2S)-2-[(2S)-2-[(2S)-2-amino-3-hydroxypropanamido]-3-(4-hydroxyphenyl)propanamido]-3-hydroxypropanamido]-4-(methylsulfanyl)butanamido]-4-carboxybutanamido]-3-(1H-imidazol-5-yl)propanamido]-3-phenylpropanamido]-5-carbamimidamidopentanamido]-3-(1H-indol-3-yl)propanamido]acetamido}hexanoyl]pyrrolidin-2-yl]formamido}-3-methylbutanamido]acetamido}hexanamido]hexanamido]-5-carbamimidamidopentanamido]-5-carbamimidamidopentanoyl]pyrrolidin-2-yl]formamido}-3-methylbutanamido]hexanamido]-3-methylbutanamido]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carboxylic acid
SMILES
CSCC[[email protected]](NC(=O)[[email protected]](CO)NC(=O)[[email protected]](CC1=CC=C(O)C=C1)NC(=O)[[email protected]@H](N)CO)C(=O)N[[email protected]@H](CCC(O)=O)C(=O)N[[email protected]@H](CC1=CN=CN1)C(=O)N[[email protected]@H](CC1=CC=CC=C1)C(=O)N[[email protected]@H](CCCNC(N)=N)C(=O)N[[email protected]@H](CC1=CNC2=C1C=CC=C2)C(=O)NCC(=O)N[[email protected]@H](CCCCN)C(=O)N1CCC[[email protected]]1C(=O)N[[email protected]@H](C(C)C)C(=O)NCC(=O)N[[email protected]@H](CCCCN)C(=O)N[[email protected]@H](CCCCN)C(=O)N[[email protected]@H](CCCNC(N)=N)C(=O)N[[email protected]@H](CCCNC(N)=N)C(=O)N1CCC[[email protected]]1C(=O)N[[email protected]@H](C(C)C)C(=O)N[[email protected]@H](CCCCN)C(=O)N[[email protected]@H](C(C)C)C(=O)N[[email protected]@H](CC1=CC=C(O)C=C1)C(=O)N1CCC[[email protected]]1C(O)=O

Pharmacology

Indication

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

Structured Indications
Pharmacodynamics

Cosyntropin exhibits the full corticosteroidogenic activity of natural ACTH. Various studies have shown that the biologic activity of ACTH resides in the N- terminal portion of the molecule and that the 1-20 amino acid residue is the minimal sequence retaining full activity. Partial or complete loss of activity is noted with progressive shortening of the chain beyond 20 amino acid residue. For example, the decrement from 20 to 19 results in a 70% loss of potency. The pharmacologic profile of Cosyntropin is similar to that of purified natural ACTH. It has been established that 0.25 mg of Cosyntropin will stimulate the adrenal cortex maximally and to the same extent as 25 units of natural ACTH. Cosyntropin has less immunogenic activity than ACTH because the amino acid sequence having most of the antigenic activity of ACTH, i.e., amino acids 25-39, is not present in cosyntropin. The extra-adrenal effects which natural ACTH and Cosyntropin have in common include increased melanotropic activity, increased growth hormone secretion and an adipokinetic effect. These are considered to be without physiological or clinical significance.

Mechanism of action

Cosyntropin combines with a specific receptor in the adrenal cell plasma membrane and, in patients with normal adrenocortical function, 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 the substrate within the mitochondria. Cosyntropin does not significantly increase plasma cortisol concentration in patients with primary or secondary adrenocortical insufficiency.

TargetActionsOrganism
AAdrenocorticotropic hormone receptor
antagonist
Human
Absorption

Rapidly absorbed following intramuscular administration.

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
DrugInteractionDrug group
ClonazepamTetracosactide may increase the hepatotoxic activities of Clonazepam.Approved, Illicit
DiazepamTetracosactide may increase the hepatotoxic activities of Diazepam.Approved, Illicit, Investigational, Vet Approved
NitrazepamTetracosactide may increase the hepatotoxic activities of Nitrazepam.Approved
PhenobarbitalTetracosactide may increase the hepatotoxic activities of Phenobarbital.Approved, Investigational
PhenytoinTetracosactide may increase the hepatotoxic activities of Phenytoin.Approved, Vet Approved
PrimidoneTetracosactide may increase the hepatotoxic activities of Primidone.Approved, Vet Approved
Valproic AcidTetracosactide may increase the hepatotoxic activities of Valproic Acid.Approved, Investigational
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Drug
D00284
KEGG Compound
C06926
PubChem Compound
16133751
PubChem Substance
46506301
ChemSpider
10481947
BindingDB
50017180
ChEBI
3901
ChEMBL
CHEMBL2103784
Therapeutic Targets Database
DAP000284
PharmGKB
PA164749052
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tetracosactide
ATC Codes
H01AA02 — Tetracosactide
AHFS Codes
  • 68:04.00 — Adrenals
  • 36:04.00 — Adrenocortical Insufficiency
  • 68:28.00 — Pituitary

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingBasic ScienceBMI >30 kg/m2 / Hyperandrogenemia / Polycystic Ovaries Syndrome1
1CompletedSupportive CareAdrenal Cortex Diseases / Infant Morbidity1
2RecruitingTreatmentMuscular Dystrophy, Duchenne1
2RecruitingTreatmentPost-Dural Puncture Headache1
3CompletedDiagnosticDevelopment1
3RecruitingDiagnosticAdrenal Insufficiency / Lecithin Acyltransferase Deficiency / Liver Cirrhosis / Spur Cell Anemia1
4CompletedBasic ScienceStress1
4CompletedDiagnosticAdrenal Insufficiency / Healthy Volunteers / Hypopituitarism1
4CompletedTreatmentAdrenal Failure1
4CompletedTreatmentPostdural Puncture Headache1
Not AvailableActive Not RecruitingOtherAutonomic Nervous System / Baroreflexes / Stress, Physiological1
Not AvailableActive Not RecruitingOtherPostural Tachycardia Syndrome1
Not AvailableCompletedScreeningPolycystic Ovaries Syndrome1
Not AvailableRecruitingBasic ScienceBMI >30 kg/m2 / Hyperandrogenemia / Polycystic Ovaries Syndrome1
Not AvailableRecruitingDiagnosticAdrenal Insufficiency1
Not AvailableUnknown StatusScreeningBrain Injury / Craniocerebral Trauma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Amphastar Pharmaceuticals
  • Generamedix Inc.
  • Sandoz
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous.25 mg/mL
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous; Parenteral.25 mg/mL
Powder, for solutionIntramuscular; Intravenous0.25 mg
Injection, powder, for solutionIntramuscular; Intravenous.25 mg/mL
Injection, powder, lyophilized, for solutionIntravenous.25 mg/mL
SuspensionIntramuscular1 mg
Prices
Unit descriptionCostUnit
Cortrosyn 0.25 mg vial127.9USD vial
Cosyntropin 0.25 mg/ml119.91USD ml
Cosyntropin 0.25 mg vial115.1USD vial
Synacthen Depot 1 mg/vial34.77USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0481 mg/mLALOGPS
logP-0.95ALOGPS
logP-14ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)3.03ChemAxon
pKa (Strongest Basic)12.38ChemAxon
Physiological Charge6ChemAxon
Hydrogen Acceptor Count46ChemAxon
Hydrogen Donor Count42ChemAxon
Polar Surface Area1158.72 Å2ChemAxon
Rotatable Bond Count93ChemAxon
Refractivity790.98 m3·mol-1ChemAxon
Polarizability309.35 Å3ChemAxon
Number of Rings9ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as polypeptides. These are peptides containing ten or more amino acid residues.
Kingdom
Organic compounds
Super Class
Organic Polymers
Class
Polypeptides
Sub Class
Not Available
Direct Parent
Polypeptides
Alternative Parents
Peptides / Tyrosine and derivatives / Arginine and derivatives / Phenylalanine and derivatives / Histidine and derivatives / Glutamic acid and derivatives / Methionine and derivatives / Valine and derivatives / Proline and derivatives / N-acyl-L-alpha-amino acids
show 30 more
Substituents
Polypeptide / Alpha peptide / Tyrosine or derivatives / Arginine or derivatives / Phenylalanine or derivatives / Histidine or derivatives / Glutamic acid or derivatives / Methionine or derivatives / N-acyl-alpha amino acid or derivatives / N-acyl-alpha-amino acid
show 61 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
polypeptide (CHEBI:3901)

Targets

Details1. Adrenocorticotropic hormone receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
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. Schwerin M, Kanitz E, Tuchscherer M, Brussow KP, Nurnberg G, Otten W: Stress-related gene expression in brain and adrenal gland of porcine fetuses and neonates. Theriogenology. 2005 Mar 1;63(4):1220-34. [PubMed:15710205]
  2. Mehrabani PA, Bassett JR: Adrenocorticotropin binding sites in rat cardiac tissue. Pharmacol Biochem Behav. 1990 Jan;35(1):99-103. [PubMed:2156274]
  3. Moraes RB, Czepielewski MA, Friedman G: Cortisol variation after low-dose Cortrosyn test. Crit Care Med. 2010 Jul;38(7):1612-3. doi: 10.1097/CCM.0b013e3181da4ef1. [PubMed:20562554]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on May 23, 2007 21:46 / Updated on April 23, 2018 23:08