Tesamorelin

Pharmaceutical drug

H01AC06 (WHO)

US: ℞-only
In general: ℞ (Prescription only)

Pharmacokinetic dataBioavailability≤4%^[1]MetabolismProteolysisElimination half-life26–38 minExcretionRenal/proteolysisIdentifiersCAS Number

218949-48-5^Y
as salt: 901758-09-6^Y

PubChem CID

16137828

ChemSpider

34982925

UNII

MQG94M5EEO
as salt: LGW5H38VE3^Y

KEGG

D09015^Y

ChEBI

CHEBI:63626

CompTox Dashboard (EPA)

DTXSID00583207

Chemical and physical dataFormulaC₂₂₁H₃₆₆N₇₂O₆₇SMolar mass5135.86 g·mol⁻¹3D model (JSmol)

Interactive image

SMILES

CCC[C@@H](C(=O)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CCSC)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)N)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](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)N)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccc(cc1)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](Cc3ccc(cc3)O)NC(=O)C/C=C/CC

InChI

InChI=1S/C220H364N72O67S/c1-24-28-30-54-162(307)259-144(92-119-55-59-121(298)60-56-119)197(342)254-115(20)178(323)275-149(96-168(315)316)198(343)255-116(21)179(324)290-171(110(15)26-3)213(358)283-146(91-118-44-31-29-32-45-118)205(350)292-173(117(22)297)214(359)284-148(95-161(229)306)204(349)288-154(104-296)209(354)279-145(93-120-57-61-122(299)62-58-120)202(347)267-130(52-41-84-247-219(239)240)186(331)266-126(47-34-36-79-222)196(341)289-170(109(13)14)211(356)282-140(87-105(5)6)182(327)251-100-165(310)257-133(64-71-156(224)301)189(334)277-143(90-108(11)12)201(346)287-151(101-293)207(352)256-114(19)177(322)263-129(51-40-83-246-218(237)238)185(330)265-125(46-33-35-78-221)188(333)276-142(89-107(9)10)200(345)278-141(88-106(7)8)199(344)272-137(67-74-159(227)304)194(339)281-150(97-169(317)318)206(351)291-172(111(16)27-4)212(357)274-139(77-86-360-23)195(340)286-152(102-294)208(353)268-131(53-42-85-248-220(241)242)187(332)270-135(65-72-157(225)302)191(336)269-132(63-70-155(223)300)181(326)250-99-164(309)258-134(68-75-166(311)312)190(335)285-153(103-295)210(355)280-147(94-160(228)305)203(348)273-136(66-73-158(226)303)192(337)271-138(69-76-167(313)314)193(338)264-124(48-37-80-243-215(231)232)180(325)249-98-163(308)252-112(17)175(320)261-127(49-38-81-244-216(233)234)183(328)253-113(18)176(321)262-128(50-39-82-245-217(235)236)184(329)260-123(43-25-2)174(230)319/h28-32,44-45,55-62,105-117,123-154,170-173,293-299H,24-27,33-43,46-54,63-104,221-222H2,1-23H3,(H2,223,300)(H2,224,301)(H2,225,302)(H2,226,303)(H2,227,304)(H2,228,305)(H2,229,306)(H2,230,319)(H,249,325)(H,250,326)(H,251,327)(H,252,308)(H,253,328)(H,254,342)(H,255,343)(H,256,352)(H,257,310)(H,258,309)(H,259,307)(H,260,329)(H,261,320)(H,262,321)(H,263,322)(H,264,338)(H,265,330)(H,266,331)(H,267,347)(H,268,353)(H,269,336)(H,270,332)(H,271,337)(H,272,344)(H,273,348)(H,274,357)(H,275,323)(H,276,333)(H,277,334)(H,278,345)(H,279,354)(H,280,355)(H,281,339)(H,282,356)(H,283,358)(H,284,359)(H,285,335)(H,286,340)(H,287,346)(H,288,349)(H,289,341)(H,290,324)(H,291,351)(H,292,350)(H,311,312)(H,313,314)(H,315,316)(H,317,318)(H4,231,232,243)(H4,233,234,244)(H4,235,236,245)(H4,237,238,246)(H4,239,240,247)(H4,241,242,248)/b30-28+/t110-,111-,112-,113-,114-,115-,116-,117+,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-,153-,154-,170-,171-,172-,173-/m0/s1
Key:VQFDKKWXORFBDI-VAVVJCQZSA-N

Tesamorelin (INN) (trade name Egrifta SV) is a synthetic form of growth-hormone-releasing hormone (GHRH) which is used in the treatment of HIV-associated lipodystrophy, approved initially in 2010. It is produced and developed by Theratechnologies, Inc. of Canada. The drug is a synthetic peptide consisting of all 44 amino acids of human GHRH with the addition of a trans-3-hexenoic acid group.^[2]

Mechanism of action

Tesamorelin is the N-terminally modified compound based on 44 amino acids sequence of human GHRH.^[3] This modified synthetic form is more potent and stable than the natural peptide. It is also more resistant to cleavage by the dipeptidyl aminopeptidase than human GHRH.^[4] It stimulates the synthesis and release of endogenous GH, with an increase in level of insulin-like growth factor (IGF-1). The released GH then binds with the receptors present on various body organs and regulates the body composition. This regulation is mainly because of the combination of anabolic and lipolytic mechanisms. However, it has been found that the main mechanisms by which Tesamorelin reduces body fat mass are lipolysis followed by reduction in triglycerides level.^[5]

Contraindication

Tesamorelin therapy may cause glucose intolerance and increase the risk of type 2-diabetes, so it is contraindicated in pregnancy.^[6] It is also contraindicated in pregnancy (category X) because it may cause harm to fetus. It is also contraindicated in patients affected by hypothalamic-pituitary axis disruption due to pituitary gland tumor, head irradiation and hypopituitarism.^[7]

Adverse effects

Injection site erythema, peripheral edema, injection site pruritus and diarrhea.^[8]

References

^ "Egrifta (tesamorelin for injection) for Subcutaneous Use. U.S. Full Prescribing Information" (PDF). EMD Serono, Inc. Archived from the original (PDF) on 18 December 2011. Retrieved 9 April 2016.
^ "FDA Application Chemistry Review" (PDF).
^ Dhillon S (May 2011). "Tesamorelin: a review of its use in the management of HIV-associated lipodystrophy". Drugs. 71 (8): 1071–1091. doi:10.2165/11202240-000000000-00000. PMID 21668043. S2CID 195681455.
^ Ferdinandi ES, Brazeau P, High K, Procter B, Fennell S, Dubreuil P (January 2007). "Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analogue". Basic & Clinical Pharmacology & Toxicology. 100 (1): 49–58. doi:10.1111/j.1742-7843.2007.00008.x. PMID 17214611.
^ Benedini S, Terruzzi I, Lazzarin A, Luzi L (2008). "Recombinant human growth hormone: rationale for use in the treatment of HIV-associated lipodystrophy". BioDrugs. 22 (2): 101–112. doi:10.2165/00063030-200822020-00003. PMID 18345707. S2CID 34340539.
^ Patel A, Gandhi H, Upaganlawar A (April 2011). "Tesamorelin: A hope for ART-induced lipodystrophy". Journal of Pharmacy & Bioallied Sciences. 3 (2): 319–320. doi:10.4103/0975-7406.80763. PMC 3103937. PMID 21687371.
^ DeRuiter J, Holston PL. "Review of Selected NMEs 2011". www.uspharmacist.com. Auburn: Health Information Designs, Inc. Retrieved 2019-06-22.
^ Falutz J, Potvin D, Mamputu JC, Assaad H, Zoltowska M, Michaud SE, et al. (March 2010). "Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension". Journal of Acquired Immune Deficiency Syndromes. 53 (3): 311–322. doi:10.1097/qai.0b013e3181cbdaff. PMID 20101189. S2CID 13613924.