Tetracosactide - DrugBank

ID Pharmacology Interactions References Trials Economics Properties Spectra Taxonomy

Targets (1)

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

MOL SDF PDB SMILES InChI

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

Ingredient	UNII	CAS	InChI Key	Details
Tetracosactide acetate	H86HJ92K8Y	22633-88-1	DFABUZLKSKOWCS-WMPFGLIOSA-N	Details

Approved Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Cortrosyn	Injection, powder, for solution	.25 mg/mL	Intramuscular; Intravenous; Parenteral	General Injectables & Vaccines	2010-03-01	2017-01-28	US
Cortrosyn	Injection, powder, lyophilized, for solution	.25 mg/mL	Intramuscular; Intravenous	Amphastar Pharmaceuticals, Inc.	2003-08-01	Not applicable	US
Cortrosyn Inj 0.25mg	Powder, for solution	0.25 mg	Intramuscular; Intravenous	Amphastar Pharmaceuticals, Inc.	1974-12-31	Not applicable	Canada
Synacthen Depot	Suspension	1 mg	Intramuscular	Mallinckrodt Specialty Pharmaceuticals Ireland Ltd.	1973-12-31	Not applicable	Canada

Approved Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Cosyntropin	Injection, powder, lyophilized, for solution	.25 mg/mL	Intravenous	Sandoz	2012-06-29	Not applicable	US
Cosyntropin	Injection, powder, for solution	.25 mg/mL	Intramuscular; Intravenous	Mylan Institutional	2013-05-08	Not applicable	US
Cosyntropin	Injection, powder, for solution	.25 mg/mL	Intramuscular; Intravenous	Mylan Institutional	2013-05-08	Not applicable	US

Approved Over the Counter Products

Not Available

Unapproved/Other Products

Not Available

International Brands

Not Available

Brand mixtures

Not Available

Categories

UNII

72YY86EA29

CAS number

16960-16-0

Weight

Average: 2933.49
Monoisotopic: 2931.580641316

Chemical Formula

C₁₃₆H₂₁₀N₄₀O₃₁S

InChI Key

ZOEFCCMDUURGSE-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.

Target	Kind	Pharmacological action	Actions	Organism	UniProt ID
Adrenocorticotropic hormone receptor	Protein	yes	antagonist	Human	Q01718	details

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

Drug	Interaction	Drug group
Clonazepam	Tetracosactide may increase the hepatotoxic activities of Clonazepam.	Approved, Illicit
Diazepam	Tetracosactide may increase the hepatotoxic activities of Diazepam.	Approved, Illicit, Vet Approved
Nitrazepam	Tetracosactide may increase the hepatotoxic activities of Nitrazepam.	Approved
Phenobarbital	Tetracosactide may increase the hepatotoxic activities of Phenobarbital.	Approved
Phenytoin	Tetracosactide may increase the hepatotoxic activities of Phenytoin.	Approved, Vet Approved
Primidone	Tetracosactide may increase the hepatotoxic activities of Primidone.	Approved, Vet Approved
Valproic Acid	Tetracosactide may increase the hepatotoxic activities of Valproic Acid.	Approved, Investigational

Food Interactions

Not Available

References

Synthesis Reference

Not Available

General References

Not Available

External Links

Resource	Link
KEGG Drug	D00284
KEGG Compound	C06926
ChemSpider	58829625
ChEBI	3901
ChEMBL	CHEMBL2103784
Therapeutic Targets Database	DAP000284
PharmGKB	PA164749052
Drug Product Database	7516
RxList	http://www.rxlist.com/cgi/generic/cortrosyn.htm
Drugs.com	http://www.drugs.com/cdi/cosyntropin.html
Wikipedia	Tetracosactide

ATC Codes

H01AA02

AHFS Codes

68:28.00

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Completed	Supportive Care	Adrenal Cortex Diseases / Infant Morbidity	1
2	Recruiting	Treatment	Post-Dural Puncture Headache	1
3	Completed	Diagnostic	Development	1
4	Completed	Treatment	Adrenal Failure	1
4	Completed	Treatment	Postdural Puncture Headache	1
4	Recruiting	Basic Science	Stress	1
4	Unknown Status	Diagnostic	Adrenal Insufficiency / Healthy Volunteers / Hypopituitarism	1
Not Available	Active Not Recruiting	Other	Postural Tachycardia Syndrome	1
Not Available	Completed	Screening	Polycystic Ovaries Syndrome	1
Not Available	Not Yet Recruiting	Basic Science	BMI >30 kg/m2 / Hyperandrogenemia / Polycystic Ovaries Syndrome	1
Not Available	Recruiting	Not Available	Autonomic Nervous System / Baroreflexes / Stress, Physiological	1
Not Available	Recruiting	Basic Science	BMI >30 kg/m2 / Hyperandrogenemia / Polycystic Ovaries Syndrome	1
Not Available	Unknown Status	Screening	Brain Injury / Craniocerebral Trauma	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Dosage forms

Form	Route	Strength
Injection, powder, for solution	Intramuscular; Intravenous; Parenteral	.25 mg/mL
Injection, powder, lyophilized, for solution	Intramuscular; Intravenous	.25 mg/mL
Powder, for solution	Intramuscular; Intravenous	0.25 mg
Injection, powder, for solution	Intramuscular; Intravenous	.25 mg/mL
Injection, powder, lyophilized, for solution	Intravenous	.25 mg/mL
Suspension	Intramuscular	1 mg

Prices

Unit description	Cost	Unit
Cortrosyn 0.25 mg vial	127.9USD	vial
Cosyntropin 0.25 mg/ml	119.91USD	ml
Cosyntropin 0.25 mg vial	115.1USD	vial
Synacthen Depot 1 mg/vial	34.77USD	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

Property	Value	Source
Water Solubility	0.0481 mg/mL	ALOGPS
logP	-0.95	ALOGPS
logP	-14	ChemAxon
logS	-4.8	ALOGPS
pKa (Strongest Acidic)	3.03	ChemAxon
pKa (Strongest Basic)	12.38	ChemAxon
Physiological Charge	6	ChemAxon
Hydrogen Acceptor Count	46	ChemAxon
Hydrogen Donor Count	42	ChemAxon
Polar Surface Area	1158.72 Å²	ChemAxon
Rotatable Bond Count	93	ChemAxon
Refractivity	790.98 m³·mol^-1	ChemAxon
Polarizability	308.6 Å³	ChemAxon
Number of Rings	9	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

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

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

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

Targets

Details

1. 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
Molecular Weight:: 33926.28 Da

References

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 ]
Mehrabani PA, Bassett JR: Adrenocorticotropin binding sites in rat cardiac tissue. Pharmacol Biochem Behav. 1990 Jan;35(1):99-103. [PubMed:2156274 ]
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 ]
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 June 11, 2017 20:31

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Structure for DB01284 (Tetracosactide)

Targets

References