Corticorelin ovine triflutate

Identification

Name
Corticorelin ovine triflutate
Accession Number
DB09067
Type
Small Molecule
Groups
Approved
Description

Corticorelin, available commercially as corticorelin ovine triflutate (tradename Acthrel), is a synthetic form of the peptide human corticotropin-releasing hormone (hCRH), a potent stimulator of adrenocorticotropic hormone (ACTH) release from the anterior pituitary. Endogenous forms hCRH are involved in the stress response and its main function is stimulation of the pituitary to release ACTH.

It is used as a diagnostic agent to evaluate the status of the pituitary-adrenal axis in the differentiation of a pituitary source from an ectopic source of excessive ACTH secretion. It provides a differential diagnosis for Cushing's disease (a pituitary source of ACTH excess) or of ectopic ACTH syndrome (an ectopic source of ACTH excess). If corticorelin injection results in an increase of plasma ACTH and cortisol, the patient is diagnosed with Cushing's disease. However, if corticorelin injection does not result in an increase of plasma ACTH and cortisol, the patient is diagnosed with ectopic ACTH syndrome.

Structure
Thumb
Synonyms
  • Corticorelin triflutate
  • Corticotropin-releasing factor (sheep hypothalamus)
  • Corticotropin-releasing factor (sheep)
  • L-seryl-L-glutaminyl-L-α-glutamyl-L-prolyl-L-prolyl-L-isoleucyl-L-seryl-L-leucyl-L-α-aspartyl-L-leucyl-L-valyl-L-phenylalanyl-L-histidyl-L-leucyl-L-leucyl-L-arginyl-L-α-glutamyl-L-valyl-L-leucyl-L-α-glutamyl-L-methionyl-L-threonyl-L-lysyl-L-alanyl-L-α-aspartyl-L-glutaminyl-L-leucyl-L-alanyl-L-glutaminyl-L-glutaminyl-L-alanyl-L-histidyl-L-seryl-L-asparaginyl-L-arginyl-L-lysyl-L-leucyl-L-leucyl-L-α-aspartyl-L-isoleucyl-L-alaninamide
  • Ovine ACTH releasing factor
  • Ovine corticotropin-releasing factor
  • Ovine CRF 41
  • Ovine CRH
  • Sheep corticotropin-releasing factor
  • Sheep corticotropin-releasing factor (1-41)
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ActhrelInjection, powder, lyophilized, for solution100 ug/2mLIntravenousFerring Pharmaceuticals1996-05-23Not applicableUs
Categories
UNII
56X54T817Q
CAS number
121249-14-7
Weight
Average: 4670.38
Monoisotopic: 4667.485744386
Chemical Formula
C205H339N59O63S
InChI Key
QEEJLLNYQOBRRM-KSHGRFHLSA-N
InChI
InChI=1S/C205H339N59O63S/c1-30-104(21)159(198(322)225-106(23)163(214)287)259-193(317)142(87-157(285)286)253-184(308)132(77-99(11)12)246-182(306)130(75-97(7)8)244-172(296)117(46-36-38-67-207)231-170(294)118(47-39-68-221-204(215)216)233-189(313)139(84-151(213)274)251-194(318)143(91-266)256-188(312)137(82-113-88-219-93-223-113)241-165(289)108(25)227-169(293)120(51-58-147(209)270)234-173(297)121(52-59-148(210)271)229-164(288)107(24)228-179(303)128(73-95(3)4)243-176(300)123(54-61-150(212)273)236-190(314)140(85-155(281)282)242-166(290)109(26)226-168(292)116(45-35-37-66-206)239-200(324)161(110(27)268)261-178(302)126(65-72-328-29)238-174(298)124(55-62-152(275)276)237-181(305)134(79-101(15)16)254-197(321)158(103(19)20)258-177(301)125(56-63-153(277)278)235-171(295)119(48-40-69-222-205(217)218)232-180(304)129(74-96(5)6)245-183(307)131(76-98(9)10)247-187(311)138(83-114-89-220-94-224-114)250-186(310)136(81-112-43-33-32-34-44-112)255-201(325)162(111(28)269)262-192(316)135(80-102(17)18)248-191(315)141(86-156(283)284)252-185(309)133(78-100(13)14)249-195(319)144(92-267)257-199(323)160(105(22)31-2)260-196(320)145-49-41-70-263(145)203(327)146-50-42-71-264(146)202(326)127(57-64-154(279)280)240-175(299)122(53-60-149(211)272)230-167(291)115(208)90-265/h32-34,43-44,88-89,93-111,115-146,158-162,265-269H,30-31,35-42,45-87,90-92,206-208H2,1-29H3,(H2,209,270)(H2,210,271)(H2,211,272)(H2,212,273)(H2,213,274)(H2,214,287)(H,219,223)(H,220,224)(H,225,322)(H,226,292)(H,227,293)(H,228,303)(H,229,288)(H,230,291)(H,231,294)(H,232,304)(H,233,313)(H,234,297)(H,235,295)(H,236,314)(H,237,305)(H,238,298)(H,239,324)(H,240,299)(H,241,289)(H,242,290)(H,243,300)(H,244,296)(H,245,307)(H,246,306)(H,247,311)(H,248,315)(H,249,319)(H,250,310)(H,251,318)(H,252,309)(H,253,308)(H,254,321)(H,255,325)(H,256,312)(H,257,323)(H,258,301)(H,259,317)(H,260,320)(H,261,302)(H,262,316)(H,275,276)(H,277,278)(H,279,280)(H,281,282)(H,283,284)(H,285,286)(H4,215,216,221)(H4,217,218,222)/t104-,105-,106-,107-,108-,109-,110+,111+,115-,116-,117-,118-,119-,120-,121-,122-,123-,124-,125-,126-,127-,128-,129-,130-,131-,132-,133-,134-,135-,136-,137-,138-,139-,140-,141-,142-,143-,144-,145-,146-,158-,159-,160-,161-,162-/m0/s1
IUPAC Name
corticorelin
SMILES
CC[C@H](C)[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CO)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)O)C(=O)N[C@@H](C)C(N)=O

Pharmacology

Indication

Corticorelin is indicated for use in differentiating pituitary and ectopic production of ACTH in patients with ACTH-dependent Cushing's syndrome.

Associated Conditions
Pharmacodynamics

In normal subjects, intravenous administration of corticorelin results in a rapid and sustained increase of plasma ACTH levels and a near parallel increase of plasma cortisol. In addition, intravenous administration of corticorelin to normal subjects causes a concomitant and prolonged release of the related proopiomelanocortin peptides β- and γ-lipotropins (β -and γ-LPH) and β-endorphin (β -END).

Mechanism of action

Corticorelin is a potent stimulator of adrenocorticotropic hormone (ACTH) release from the anterior pituitary. It is used as a diagnostic agent to evaluate the status of the pituitary-adrenal axis in the differentiation of a pituitary source from an ectopic source of excessive ACTH secretion.

TargetActionsOrganism
ACorticotropin-releasing factor receptor 1
ligand
Absorption

Plasma ACTH levels in normal subjects increased 2 minutes after injection of corticorelin doses of ≥0.3 mcg/kg and reached peak levels after 10-15 minutes. Plasma cortisol levels increased within 10 minutes and reached peak levels at 30 to 60 minutes.

Volume of distribution

The mean volume of distribution for IR-corticorelin is 6.2 ± 0.5 L

Protein binding

Corticorelin does not appear to be bound specifically by a circulating plasma protein.

Metabolism
Not Available
Route of elimination
Not Available
Half life

Plasma half-lives for IR-corticorelin are 11.6 ± 1.5 minutes (mean ± SE) for the fast component and 73 ± 8 minutes for the slow component.

Clearance

95 ± 11 L/m2/day

Toxicity

The severity of adverse effects to a corticorelin injection appear to be dose-dependent. Dosages above 1 mcg/kg are not recommended. While few adverse effects have been observed at the 1 mcg/kg or 100 mcg dose, higher doses have been associated with transient tachycardia, decreased blood pressure, loss of consciousness, and asystole.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
16-BromoepiandrosteroneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with 16-Bromoepiandrosterone.Investigational
19-norandrostenedioneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with 19-norandrostenedione.Experimental, Illicit
5-androstenedioneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with 5-androstenedione.Experimental, Illicit
AlclometasoneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Alclometasone.Approved
AldosteroneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Aldosterone.Experimental, Investigational
AmcinonideThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Amcinonide.Approved
AndrostenedioneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Androstenedione.Experimental, Illicit
AnecortaveThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Anecortave.Investigational
anecortave acetateThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with anecortave acetate.Investigational
AtamestaneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Atamestane.Investigational
Beclomethasone dipropionateThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Beclomethasone dipropionate.Approved, Investigational
BetamethasoneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Betamethasone.Approved, Vet Approved
BudesonideThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Budesonide.Approved
CiclesonideThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Ciclesonide.Approved, Investigational
ClobetasolThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Clobetasol.Approved, Investigational
Clobetasol propionateThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Clobetasol propionate.Approved
ClobetasoneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Clobetasone.Approved
ClocortoloneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Clocortolone.Approved
Cortexolone 17α-propionateThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Cortexolone 17α-propionate.Investigational
CorticosteroneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Corticosterone.Experimental
Cortisone acetateThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Cortisone acetate.Approved, Investigational
DeflazacortThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Deflazacort.Approved, Investigational
DesonideThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Desonide.Approved, Investigational
DesoximetasoneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Desoximetasone.Approved
Desoxycorticosterone acetateThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Desoxycorticosterone acetate.Approved
Desoxycorticosterone PivalateThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Desoxycorticosterone Pivalate.Experimental, Vet Approved
DexamethasoneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Dexamethasone.Approved, Investigational, Vet Approved
Dexamethasone isonicotinateThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Dexamethasone isonicotinate.Vet Approved
DiflorasoneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Diflorasone.Approved
DifluocortoloneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Difluocortolone.Approved, Investigational, Withdrawn
DifluprednateThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Difluprednate.Approved
EquileninThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Equilenin.Experimental
EquilinThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Equilin.Approved
EstroneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Estrone.Approved
Estrone sulfateThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Estrone sulfate.Approved
FluasteroneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Fluasterone.Investigational
FludrocortisoneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Fludrocortisone.Approved, Investigational
FlumethasoneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Flumethasone.Approved, Vet Approved
FlunisolideThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Flunisolide.Approved, Investigational
Fluocinolone AcetonideThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Fluocinolone Acetonide.Approved, Investigational, Vet Approved
FluocinonideThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Fluocinonide.Approved, Investigational
FluocortoloneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Fluocortolone.Approved, Withdrawn
FluorometholoneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Fluorometholone.Approved, Investigational
FluprednideneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Fluprednidene.Approved, Withdrawn
FluprednisoloneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Fluprednisolone.Approved
FlurandrenolideThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Flurandrenolide.Approved
FluticasoneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Fluticasone.Approved, Experimental, Investigational
Fluticasone furoateThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Fluticasone furoate.Approved
Fluticasone propionateThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Fluticasone propionate.Approved
FormestaneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Formestane.Approved, Investigational, Withdrawn
HalcinonideThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Halcinonide.Approved, Investigational, Withdrawn
HE3286The therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with HE3286.Investigational
HeparinThe risk or severity of adverse effects can be increased when Heparin is combined with Corticorelin ovine triflutate.Approved, Investigational
HydrocortisoneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Hydrocortisone.Approved, Vet Approved
IstaroximeThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Istaroxime.Investigational
LoteprednolThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Loteprednol.Approved
ME-609The therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with ME-609.Investigational
MedrysoneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Medrysone.Approved
MelengestrolThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Melengestrol.Vet Approved
MethylprednisoloneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Methylprednisolone.Approved, Vet Approved
MometasoneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Mometasone.Approved, Vet Approved
NCX 1022The therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with NCX 1022.Investigational
Oleoyl-estroneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Oleoyl-estrone.Investigational
ParamethasoneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Paramethasone.Approved
PrasteroneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Prasterone.Approved, Investigational, Nutraceutical
Prasterone sulfateThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Prasterone sulfate.Investigational
PrednicarbateThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Prednicarbate.Approved, Investigational
PrednisoloneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Prednisolone.Approved, Vet Approved
PrednisoneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Prednisone.Approved, Vet Approved
PregnenoloneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Pregnenolone.Approved, Experimental, Investigational
RimexoloneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Rimexolone.Approved
TixocortolThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Tixocortol.Approved, Withdrawn
TriamcinoloneThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Triamcinolone.Approved, Vet Approved
UlobetasolThe therapeutic efficacy of Corticorelin ovine triflutate can be decreased when used in combination with Ulobetasol.Approved
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Drug
D03592
PubChem Compound
16132344
PubChem Substance
310265000
ChemSpider
17289003
ChEBI
65307
ChEMBL
CHEMBL1201591
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Corticorelin
FDA label
Download (2.56 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedDiagnosticPituitary Neoplasms1
1CompletedBasic ScienceStress1
Not AvailableCompletedNot AvailableCocaine-Related Disorders / Dependence, Cocaine / Substance-Related Disorders1
Not AvailableCompletedNot AvailableDependence, Cocaine1
Not AvailableNot Yet RecruitingBasic ScienceFunctional Dyspepsia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous100 ug/2mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
logP-27ChemAxon
pKa (Strongest Acidic)2.87ChemAxon
pKa (Strongest Basic)12.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count74ChemAxon
Hydrogen Donor Count66ChemAxon
Polar Surface Area1989.13 Å2ChemAxon
Rotatable Bond Count159ChemAxon
Refractivity1178.82 m3·mol-1ChemAxon
Polarizability485.81 Å3ChemAxon
Number of Rings5ChemAxon
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
Hexacarboxylic acids and derivatives / Peptides / Arginine and derivatives / Phenylalanine and derivatives / Histidine and derivatives / Glutamic acid and derivatives / Glutamine and derivatives / Asparagine and derivatives / Aspartic acid and derivatives / Isoleucine and derivatives
show 32 more
Substituents
Polypeptide / Hexacarboxylic acid or derivatives / Alpha peptide / Arginine or derivatives / Phenylalanine or derivatives / Histidine or derivatives / Glutamic acid or derivatives / Glutamine or derivatives / Methionine or derivatives / Asparagine or derivatives
show 56 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Not Available
Pharmacological action
Yes
Actions
Ligand
General Function
G-protein coupled receptor for CRH (corticotropin-releasing factor) and UCN (urocortin). Has high affinity for CRH and UCN. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and down-stream effectors, such as adenylate cyclase. Promotes the activation of adenylate cyclase, leading to increased intracellular cAMP levels. Inhibits the activity of the calcium channel CACNA1H. Required for normal embryonic development of the adrenal gland and for normal hormonal responses to stress. Plays a role in the response to anxiogenic stimuli.
Specific Function
Corticotrophin-releasing factor receptor activity
Gene Name
CRHR1
Uniprot ID
P34998
Uniprot Name
Corticotropin-releasing factor receptor 1
Molecular Weight
50718.755 Da

Drug created on May 11, 2015 16:48 / Updated on June 02, 2018 08:16