Identification

Name
Tesamorelin
Accession Number
DB08869
Type
Small Molecule
Groups
Approved, 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 Key
Tesamorelin acetateLGW5H38VE3901758-09-6Not applicable
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EgriftaKit1 mg/1mLSubcutaneousEmd Serono2010-12-162014-11-30Us
EgriftaKit; Powder, for solution2 mgSubcutaneousTheratechnologiesNot applicableNot applicableCanada
EgriftaKit1 mg/1mLSubcutaneousTheratechnologies Inc.2014-07-14Not applicableUs
EgriftaKit2 mg/2mLSubcutaneousEmd Serono2012-09-052018-08-01Us
EgriftaKit2 mg/2mLSubcutaneousTheratechnologies2014-04-162014-08-25Us
EgriftaKit; Powder, for solution1 mgSubcutaneousTheratechnologies2015-06-23Not applicableCanada
Categories
UNII
MQG94M5EEO
CAS number
218949-48-5
Weight
Average: 5005.76
Monoisotopic: 5002.690032114
Chemical Formula
C216H360N72O63S
InChI Key
LAJJBLZKAIOLRM-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.

Associated Conditions
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.

TargetActionsOrganism
AGrowth hormone-releasing hormone receptor
binder
Human
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 binding
Not Available
Metabolism

No formal metabolism studies have been performed in humans.

Route of elimination
Not Available
Half life

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

Clearance
Not 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
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.
PrednisoloneThe serum concentration of Prednisolone can be decreased when it is combined with Tesamorelin.
PrednisoneThe serum concentration of Prednisone can be decreased when it is combined with Tesamorelin.
Food Interactions
Not Available

References

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
UniProt
P01286
KEGG Drug
D09015
PubChem Compound
56928011
PubChem Substance
347827804
ChemSpider
34999256
ChEBI
63626
ChEMBL
CHEMBL1237026
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Tesamorelin
ATC Codes
H01AC06 — Tesamorelin
AHFS Codes
  • 68:30.04 — Somatotropin Agonists*
FDA label
Download (1.53 MB)
MSDS
Download (568 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHuman Immunodeficiency Virus (HIV)1
1RecruitingTreatmentMild Cognitive Impairment (MCI)1
2CompletedTreatmentHuman Growth Hormone Deficiency / Obesity, Abdominal1
2CompletedTreatmentType 2 Diabetes Mellitus1
2Not Yet RecruitingTreatmentBMI >30 kg/m2 / Fatty Liver / Liver Fat / Non-Alcoholic Fatty Liver Disease (NAFLD) / Obesity, Abdominal1
2RecruitingTreatmentMild Cognitive Impairment (MCI)1
2RecruitingTreatmentPeripheral Nerve Injury (PNI)1
2TerminatedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
2WithdrawnTreatmentSleep Disorder / Traumatic Brain Injury (TBI)1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Lipodystrophies2
4RecruitingTreatmentBody Composition / HIV Lipodystrophy Syndrome / Human Growth Hormone Deficiency1
4TerminatedPreventionHuman Immunodeficiency Virus (HIV) / Retinopathy, Diabetic1
Not AvailableActive Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) / Nonalcoholic Fatty Liver Disease (NAFLD) / Nonalcoholic Steatohepatitis (NASH)1
Not AvailableCompletedTreatmentHIV Lipodystrophy / Human Immunodeficiency Virus (HIV)1
Not AvailableCompletedTreatmentHealthy Volunteers1
Not AvailableTerminatedNot AvailableHuman Immunodeficiency Virus (HIV)1
Not AvailableWithdrawnNot AvailableLipodystrophies1
Not AvailableWithdrawnTreatmentObesity, Abdominal1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
KitSubcutaneous1 mg/1mL
KitSubcutaneous2 mg/2mL
Kit; powder, for solutionSubcutaneous1 mg
Kit; powder, for solutionSubcutaneous2 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7144577No2000-07-142020-07-14Us
US7316997No2003-08-142023-08-14Us
US5861379No2000-05-262020-05-26Us

Properties

State
Solid
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 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 / Glutamine and derivatives / Asparagine and derivatives / Aspartic acid and derivatives / Isoleucine and derivatives / Leucine and derivatives / Methionine and derivatives
show 25 more
Substituents
Polypeptide / Alpha peptide / Tyrosine or derivatives / Arginine or derivatives / Phenylalanine or derivatives / Glutamine or derivatives / Methionine or derivatives / Asparagine or derivatives / Aspartic acid or derivatives / Leucine or derivatives
show 46 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
polypeptide, 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
Uniprot Name
Growth hormone-releasing hormone receptor
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 November 13, 2018 08:04