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Identification
NameTesamorelin
Accession NumberDB08869
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionTesamorelin is a stabilized synthetic peptide analogue of the hypothalamic peptide, Growth Hormone Releasing Hormone (GHRH) indicated for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy. Lipodystrophy is a metabolic condition characterized by insulin resistance, fat redistribution, and hyperlipidemia associated with antiretroviral therapy for HIV infection.
Structure
Thumb
Synonyms
GHRH(1-44)
N-[(3E)-1-oxo-3-hexenyl]Somatoliberin (human pancreatic islet)
External Identifiers
  • TH-9507
  • TH9507
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EgriftakitsubcutaneousEMD Serono, Inc.2012-09-05Not applicableUs
EgriftakitsubcutaneousTheratechnologies Inc.2014-07-14Not applicableUs
Egriftakit; powder for solution2 mgsubcutaneousTheratechnologies IncNot applicableNot applicableCanada
Egriftakit; powder for solution1 mgsubcutaneousTheratechnologies Inc2015-06-23Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Tesamorelin acetate
901758-09-6
ThumbNot applicableDBSALT001835
Categories
UNIIMQG94M5EEO
CAS number218949-48-5
WeightAverage: 5005.76
Monoisotopic: 5002.690032114
Chemical FormulaC216H360N72O63S
InChI KeyLAJJBLZKAIOLRM-YHAVXTEWSA-N
InChI
InChI=1S/C216H360N72O63S/c1-25-28-30-53-161(304)256-142(90-118-54-58-120(294)59-55-118)193(334)251-114(21)175(316)271-147(94-165(308)309)194(335)252-115(22)176(317)286-168(109(16)26-2)209(350)279-144(89-117-43-31-29-32-44-117)201(342)288-170(116(23)293)210(351)280-146(93-160(226)303)200(341)284-152(102-292)205(346)275-143(91-119-56-60-121(295)61-57-119)198(339)263-128(51-41-81-244-215(236)237)182(323)262-124(46-34-36-76-218)192(333)285-167(108(14)15)207(348)278-138(85-104(6)7)179(320)248-98-164(307)254-131(63-69-154(220)297)186(327)273-141(88-107(12)13)197(338)283-149(99-289)203(344)253-113(20)174(315)258-126(49-39-79-242-213(232)233)181(322)261-123(45-33-35-75-217)185(326)272-140(87-106(10)11)196(337)274-139(86-105(8)9)195(336)267-135(67-73-158(224)301)190(331)277-148(95-166(310)311)202(343)287-169(110(17)27-3)208(349)269-136(74-83-352-24)191(332)282-150(100-290)204(345)264-129(52-42-82-245-216(238)239)183(324)266-133(65-71-156(222)299)189(330)265-130(62-68-153(219)296)178(319)247-97-163(306)255-132(64-70-155(221)298)187(328)281-151(101-291)206(347)276-145(92-159(225)302)199(340)268-134(66-72-157(223)300)188(329)260-122(47-37-77-240-211(228)229)177(318)246-96-162(305)249-111(18)172(313)257-125(48-38-78-241-212(230)231)180(321)250-112(19)173(314)259-127(50-40-80-243-214(234)235)184(325)270-137(171(227)312)84-103(4)5/h28-32,43-44,54-61,103-116,122-152,167-170,289-295H,25-27,33-42,45-53,62-102,217-218H2,1-24H3,(H2,219,296)(H2,220,297)(H2,221,298)(H2,222,299)(H2,223,300)(H2,224,301)(H2,225,302)(H2,226,303)(H2,227,312)(H,246,318)(H,247,319)(H,248,320)(H,249,305)(H,250,321)(H,251,334)(H,252,335)(H,253,344)(H,254,307)(H,255,306)(H,256,304)(H,257,313)(H,258,315)(H,259,314)(H,260,329)(H,261,322)(H,262,323)(H,263,339)(H,264,345)(H,265,330)(H,266,324)(H,267,336)(H,268,340)(H,269,349)(H,270,325)(H,271,316)(H,272,326)(H,273,327)(H,274,337)(H,275,346)(H,276,347)(H,277,331)(H,278,348)(H,279,350)(H,280,351)(H,281,328)(H,282,332)(H,283,338)(H,284,341)(H,285,333)(H,286,317)(H,287,343)(H,288,342)(H,308,309)(H,310,311)(H4,228,229,240)(H4,230,231,241)(H4,232,233,242)(H4,234,235,243)(H4,236,237,244)(H4,238,239,245)/b30-28+/t109?,110?,111-,112-,113-,114-,115-,116?,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-,147-,148-,149-,150-,151-,152-,167-,168-,169-,170-/m0/s1
IUPAC Name
SMILES
CC\C=C\CC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)CC)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)CC)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(N)=O
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
  • Glutamine or derivatives
  • Leucine or derivatives
  • Isoleucine or derivatives
  • Aspartic acid or derivatives
  • Asparagine or derivatives
  • Methionine or derivatives
  • N-acyl-alpha amino acid or derivatives
  • Valine or derivatives
  • Serine or derivatives
  • Alpha-amino acid amide
  • Alanine or derivatives
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Amphetamine or derivatives
  • 1-hydroxy-2-unsubstituted benzenoid
  • Phenol
  • Monocyclic benzene moiety
  • Dicarboxylic acid or derivatives
  • Fatty amide
  • N-acyl-amine
  • Fatty acyl
  • Benzenoid
  • Primary carboxylic acid amide
  • Amino acid or derivatives
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Amino acid
  • Carboxamide group
  • Guanidine
  • Sulfenyl compound
  • Dialkylthioether
  • Carboximidamide
  • Thioether
  • Carboxylic acid derivative
  • Carboxylic acid
  • Primary amine
  • Organic oxygen compound
  • Organic nitrogen compound
  • Imine
  • Primary aliphatic amine
  • Organic oxide
  • Carbonyl group
  • Alcohol
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organooxygen compound
  • Organosulfur compound
  • Amine
  • Primary alcohol
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationTesamorelin acetate is a synthetic analogue of human hypothalamic Growth Hormone Releasing Factor (hGRF) indicated to induce and maintain a reduction of excess abdominal fat in HIV-infected patients with lipodystrophy.
PharmacodynamicsTesamorelin stimulates growth hormone secretion, and subsequently increases IGF-1 and IGFBP-3 levels.
Mechanism of actionBy acting on the pituitary cells in the brain, tesamorelin stimulates production and release of the endogenous hormone (hGRF). Tesamorelin therapy predisposes the patient to glucose intolerance and can also increase the risk of type 2 diabetes, so the drug is contraindicated in pregnancy.
Related Articles
AbsorptionThe absolute bioavailability was determined to be less than 4% in healthy adult subjects following a 2 mg subcutaneous dose.
Volume of distribution

9.4±3.1 L/kg in healthy subjects.
10.5±6.1 L/kg in HIV-infected patients.

Protein bindingNot Available
Metabolism

No formal metabolism studies have been performed in humans.

Route of eliminationNot Available
Half life26 and 38 minutes in healthy subjects and HIV-infected patients, respectively.
ClearanceNot Available
ToxicityDiarrhea, congestive heart failure, peripheral neuropathy, and loss of mobility were the four serious adverse events reported during the clinical studies
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal AbsorptionNot AvailableNot Available
Blood Brain BarrierNot AvailableNot Available
Caco-2 permeableNot AvailableNot Available
P-glycoprotein substrateNot AvailableNot Available
P-glycoprotein inhibitor INot AvailableNot Available
P-glycoprotein inhibitor IINot AvailableNot Available
Renal organic cation transporterNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 1A2 substrateNot AvailableNot Available
CYP450 2C9 inhibitorNot AvailableNot Available
CYP450 2D6 inhibitorNot AvailableNot Available
CYP450 2C19 inhibitorNot AvailableNot Available
CYP450 3A4 inhibitorNot AvailableNot Available
CYP450 inhibitory promiscuityNot AvailableNot Available
Ames testNot AvailableNot Available
CarcinogenicityNot AvailableNot Available
BiodegradationNot AvailableNot Available
Rat acute toxicityNot AvailableNot applicable
hERG inhibition (predictor I)Not AvailableNot Available
hERG inhibition (predictor II)Not AvailableNot Available
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Kitsubcutaneous
Kit; powder for solutionsubcutaneous1 mg
Kit; powder for solutionsubcutaneous2 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5861379 No2000-05-262020-05-26Us
US7144577 No2000-07-142020-07-14Us
US7316997 No2003-08-142023-08-14Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
Predicted Properties
PropertyValueSource
logP-35ChemAxon
pKa (Strongest Acidic)3.28ChemAxon
pKa (Strongest Basic)12.7ChemAxon
Physiological Charge6ChemAxon
Hydrogen Acceptor Count83ChemAxon
Hydrogen Donor Count81ChemAxon
Polar Surface Area2278.76 Å2ChemAxon
Rotatable Bond Count176ChemAxon
Refractivity1314.56 m3·mol-1ChemAxon
Polarizability505.02 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Spooner LM, Olin JL: Tesamorelin: a growth hormone-releasing factor analogue for HIV-associated lipodystrophy. Ann Pharmacother. 2012 Feb;46(2):240-7. doi: 10.1345/aph.1Q629. Epub 2012 Jan 31. [PubMed:22298602 ]
  2. McLarnon A: Neuroendocrinology: Tesamorelin can improve cognitive function. Nat Rev Endocrinol. 2012 Oct;8(10):568. doi: 10.1038/nrendo.2012.151. Epub 2012 Aug 28. [PubMed:22926095 ]
  3. Bedimo R: Growth hormone and tesamorelin in the management of HIV-associated lipodystrophy. HIV AIDS (Auckl). 2011;3:69-79. doi: 10.2147/HIV.S14561. Epub 2011 Jul 10. [PubMed:22096409 ]
  4. Dhillon S: Spotlight on tesamorelin in HIV-associated lipodystrophy. BioDrugs. 2011 Dec 1;25(6):405-8. doi: 10.2165/11208290-000000000-00000. [PubMed:22050344 ]
  5. Garg A: Acquired and inherited lipodystrophies. N Engl J Med. 2004 Mar 18;350(12):1220-34. [PubMed:15028826 ]
  6. Patel A, Gandhi H, Upaganlawar A: Tesamorelin: A hope for ART-induced lipodystrophy. J Pharm Bioallied Sci. 2011 Apr;3(2):319-20. doi: 10.4103/0975-7406.80763. [PubMed:21687371 ]
  7. Campbell RM, Lee Y, Rivier J, Heimer EP, Felix AM, Mowles TF: GRF analogs and fragments: correlation between receptor binding, activity and structure. Peptides. 1991 May-Jun;12(3):569-74. [PubMed:1656403 ]
External Links
ATC CodesH01AC06
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (1.53 MB)
MSDSDownload (568 KB)
Interactions
Drug Interactions
Drug
Cortisone acetateThe serum concentration of the active metabolites of Cortisone acetate can be reduced when Cortisone acetate is used in combination with Tesamorelin resulting in a loss in efficacy.
PrednisoneThe serum concentration of the active metabolites of Prednisone can be reduced when Prednisone is used in combination with Tesamorelin resulting in a loss in efficacy.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
binder
General Function:
Peptide hormone binding
Specific Function:
Receptor for GRF, coupled to G proteins which activate adenylyl cyclase. Stimulates somatotroph cell growth, growth hormone gene transcription and growth hormone secretion.
Gene Name:
GHRHR
Uniprot ID:
Q02643
Molecular Weight:
47401.53 Da
References
  1. Spooner LM, Olin JL: Tesamorelin: a growth hormone-releasing factor analogue for HIV-associated lipodystrophy. Ann Pharmacother. 2012 Feb;46(2):240-7. doi: 10.1345/aph.1Q629. Epub 2012 Jan 31. [PubMed:22298602 ]
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Drug created on April 30, 2013 18:36 / Updated on September 24, 2016 02:16