Identification
NameTetracosactide
Accession NumberDB01284
TypeSmall Molecule
GroupsApproved
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
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
External IDs Not Available
Product Ingredients
IngredientUNIICASInChI KeyDetails
Tetracosactide acetateH86HJ92K8Y 22633-88-1DFABUZLKSKOWCS-WMPFGLIOSA-NDetails
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CortrosynInjection, powder, for solution.25 mg/mLIntramuscular; Intravenous; ParenteralGeneral Injectables & Vaccines2010-03-012017-01-28Us
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
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CosyntropinInjection, powder, lyophilized, for solution.25 mg/mLIntravenousSandoz2012-06-29Not applicableUs
CosyntropinInjection, powder, for solution.25 mg/mLIntramuscular; IntravenousMylan Institutional2013-05-08Not applicableUs
CosyntropinInjection, powder, for solution.25 mg/mLIntramuscular; IntravenousMylan Institutional2013-05-08Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNII72YY86EA29
CAS number16960-16-0
WeightAverage: 2933.49
Monoisotopic: 2931.580641316
Chemical FormulaC136H210N40O31S
InChI KeyZOEFCCMDUURGSE-XWTFHMIISA-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+/m1/s1
IUPAC Name
(2S)-1-[(2S)-2-[(2S)-2-[(2S)-6-amino-2-[(2S)-2-{[(2S)-1-[(2R)-2-[(2R)-2-[(2R)-6-amino-2-[(2R)-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-[(2R)-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]](N)CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=CC=CC=C12)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1CCC[[email protected]]1C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[[email protected]](CCCCN)C(=O)N[[email protected]](CCCCN)C(=O)N[[email protected]](CCCNC(N)=N)C(=O)N[[email protected]](CCCNC(N)=N)C(=O)N1CCC[[email protected]]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Adrenocorticotropic hormone receptorProteinyes
antagonist
HumanQ01718 details
Related Articles
Absorption

Rapidly absorbed following intramuscular administration.

Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life

About 15 minutes following intravenous administration.

ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot 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, Vet Approved
NitrazepamTetracosactide may increase the hepatotoxic activities of Nitrazepam.Approved
PhenobarbitalTetracosactide may increase the hepatotoxic activities of Phenobarbital.Approved
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 InteractionsNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesH01AA02
AHFS Codes
  • 68:28.00
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedSupportive CareAdrenal Cortex Diseases / Infant Morbidity1
2RecruitingTreatmentPost-Dural Puncture Headache1
3CompletedDiagnosticDevelopment1
4CompletedTreatmentAdrenal Failure1
4CompletedTreatmentPostdural Puncture Headache1
4RecruitingBasic ScienceStress1
4Unknown StatusDiagnosticAdrenal Insufficiency / Healthy Volunteers / Hypopituitarism1
Not AvailableActive Not RecruitingOtherPostural Tachycardia Syndrome1
Not AvailableCompletedScreeningPolycystic Ovaries Syndrome1
Not AvailableNot Yet RecruitingBasic ScienceBMI >30 kg/m2 / Hyperandrogenemia / Polycystic Ovaries Syndrome1
Not AvailableRecruitingNot AvailableAutonomic Nervous System / Baroreflexes / Stress, Physiological1
Not AvailableRecruitingBasic ScienceBMI >30 kg/m2 / Hyperandrogenemia / Polycystic Ovaries Syndrome1
Not AvailableUnknown StatusScreeningBrain Injury / Craniocerebral Trauma1
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntramuscular; Intravenous; Parenteral.25 mg/mL
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous.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.
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot 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
Polarizability308.6 Å3ChemAxon
Number of Rings9ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET featuresNot Available
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as polypeptides. These are peptides containing ten or more amino acid residues.
KingdomOrganic compounds
Super ClassOrganic Polymers
ClassPolypeptides
Sub ClassNot Available
Direct ParentPolypeptides
Alternative Parents
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
  • N-acyl-l-alpha-amino acid
  • Valine or derivatives
  • Proline or derivatives
  • Alpha-amino acid amide
  • Serine or derivatives
  • Triptan
  • N-substituted-alpha-amino acid
  • Amphetamine or derivatives
  • Alpha-amino acid or derivatives
  • 3-alkylindole
  • Indole
  • Indole or derivatives
  • Pyrrolidine-2-carboxamide
  • Imidazolyl carboxylic acid derivative
  • N-acylpyrrolidine
  • Pyrrolidine carboxylic acid or derivatives
  • Pyrrolidine carboxylic acid
  • Phenol
  • 1-hydroxy-2-unsubstituted benzenoid
  • N-acyl-amine
  • Substituted pyrrole
  • Benzenoid
  • Fatty acyl
  • Fatty amide
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Azole
  • Heteroaromatic compound
  • Imidazole
  • Tertiary carboxylic acid amide
  • Pyrrolidine
  • Pyrrole
  • Amino acid or derivatives
  • Secondary carboxylic acid amide
  • Amino acid
  • Carboxamide group
  • Guanidine
  • Thioether
  • Carboximidamide
  • Sulfenyl compound
  • Dialkylthioether
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Azacycle
  • Carboxylic acid
  • Organooxygen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxygen compound
  • Imine
  • Primary aliphatic amine
  • Carbonyl group
  • Organopnictogen compound
  • Alcohol
  • Organic oxide
  • Organosulfur compound
  • Organonitrogen compound
  • Amine
  • Primary alcohol
  • Primary amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available

Targets

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
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 May 19, 2017 16:52