Identification
NameTesamorelin
Accession NumberDB08869
TypeSmall Molecule
GroupsApproved, Investigational
Description

Tesamorelin 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 IDs TH-9507 / TH9507
Product Ingredients
IngredientUNIICASInChI KeyDetails
Tesamorelin acetateLGW5H38VE3 901758-09-6Not applicableDetails
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EgriftaKitSubcutaneousEmd Serono2012-09-05Not applicableUs
EgriftaKitSubcutaneousTheratechnologies2014-07-14Not applicableUs
EgriftaKit; Powder, for solution2 mgSubcutaneousTheratechnologiesNot applicableNot applicableCanada
EgriftaKit; Powder, for solution1 mgSubcutaneousTheratechnologies2015-06-23Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
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
Pharmacology
Indication

Tesamorelin 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.

Structured Indications
Pharmacodynamics

Tesamorelin stimulates growth hormone secretion, and subsequently increases IGF-1 and IGFBP-3 levels.

Mechanism of action

By 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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Growth hormone-releasing hormone receptorProteinyes
binder
HumanQ02643 details
Related Articles
Absorption

The 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 life

26 and 38 minutes in healthy subjects and HIV-infected patients, respectively.

ClearanceNot Available
Toxicity

Diarrhea, 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
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
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.Approved
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.Approved, Vet Approved
Food InteractionsNot 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 — Tesamorelin
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (1.53 MB)
MSDSDownload (568 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHIV Disease1
1RecruitingTreatmentMild Cognitive Impairment (MCI)1
2CompletedTreatmentGrowth Hormone Deficiency (GHD) / Obesity, Abdominal1
2CompletedTreatmentType 2 Diabetes Mellitus1
2Not Yet RecruitingTreatmentPeripheral Nerve Injury (PNI)1
2RecruitingTreatmentMild Cognitive Impairment (MCI)1
2TerminatedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
2WithdrawnTreatmentSleep Disorder / Traumatic Brain Injury (TBI)1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Lipodystrophies2
4RecruitingPreventionHIV Disease / Retinopathy, Diabetic1
Not AvailableCompletedTreatmentHIV Disease / HIV Lipodystrophy1
Not AvailableCompletedTreatmentHealthy Volunteers1
Not AvailableRecruitingNot AvailableHIV Disease1
Not AvailableRecruitingTreatmentHuman Immunodeficiency Virus (HIV) / Nonalcoholic Fatty Liver Disease (NAFLD) / Nonalcoholic Steatohepatitis (NASH)1
Not AvailableWithdrawnNot AvailableLipodystrophies1
Not AvailableWithdrawnTreatmentObesity, Abdominal1
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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
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 ParentsPeptides / Tyrosine and derivatives / Arginine and derivatives / Phenylalanine and derivatives / Glutamine and derivatives / Asparagine and derivatives / Aspartic acid and derivatives / Isoleucine and derivatives / Leucine and derivatives / Methionine and derivatives
SubstituentsPolypeptide / 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
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptorspolypeptide, peptide hormone (CHEBI:63626 )

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 ]
Drug created on April 30, 2013 18:36 / Updated on July 22, 2017 18:10