Tesamorelin

Last updated
Tesamorelin
Tesamorelin.svg
Clinical data
Trade names Egrifta SV
AHFS/Drugs.com Multum Consumer Information
MedlinePlus a611035
Routes of
administration 		Subcutaneous injection
ATC code
Legal status
Legal status
  • US: ℞-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability ≤4% [1]
Metabolism Proteolysis
Elimination half-life 26–38 min
Excretion Renal/proteolysis
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
CompTox Dashboard (EPA)
Chemical and physical data
Formula C221H366N72O67S
Molar mass 5135.86 g·mol−1
3D model (JSmol)
  • 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=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]

Contents

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]

See also

Related Research Articles

<span class="mw-page-title-main">Growth hormone</span> Peptide hormone, that stimulates growth

Growth hormone (GH) or somatotropin, also known as human growth hormone in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in human development. GH also stimulates production of IGF-1 and increases the concentration of glucose and free fatty acids. It is a type of mitogen which is specific only to the receptors on certain types of cells. GH is a 191-amino acid, single-chain polypeptide that is synthesized, stored and secreted by somatotropic cells within the lateral wings of the anterior pituitary gland.

<span class="mw-page-title-main">Vasopressin</span> Mammalian hormone released from the pituitary gland

Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travels down the axon terminating in the posterior pituitary, and is released from vesicles into the circulation in response to extracellular fluid hypertonicity (hyperosmolality). AVP has two primary functions. First, it increases the amount of solute-free water reabsorbed back into the circulation from the filtrate in the kidney tubules of the nephrons. Second, AVP constricts arterioles, which increases peripheral vascular resistance and raises arterial blood pressure.

<span class="mw-page-title-main">Human chorionic gonadotropin</span> Hormone

Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo, which eventually forms the placenta after implantation. The presence of hCG is detected in some pregnancy tests. Some cancerous tumors produce this hormone; therefore, elevated levels measured when the patient is not pregnant may lead to a cancer diagnosis and, if high enough, paraneoplastic syndromes, however, it is not known whether this production is a contributing cause, or an effect of carcinogenesis. The pituitary analog of hCG, known as luteinizing hormone (LH), is produced in the pituitary gland of males and females of all ages.

<span class="mw-page-title-main">Somatostatin</span> Peptide hormone that regulates the endocrine system

Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones. Somatostatin inhibits insulin and glucagon secretion.

<span class="mw-page-title-main">Insulin-like growth factor 1</span> Protein-coding gene in the species Homo sapiens

Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults.

<span class="mw-page-title-main">Gonadotropin-releasing hormone</span> Mammalian protein found in Homo sapiens

Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and released from GnRH neurons within the hypothalamus. The peptide belongs to gonadotropin-releasing hormone family. It constitutes the initial step in the hypothalamic–pituitary–gonadal axis.

<span class="mw-page-title-main">Octreotide</span> Octapeptide that mimics natural somatostatin pharmacologically

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<span class="mw-page-title-main">Motilin</span>

Motilin is a 22-amino acid polypeptide hormone in the motilin family that, in humans, is encoded by the MLN gene.

Growth hormone–releasing hormone (GHRH), also known as somatocrinin or by several other names in its endogenous forms and as somatorelin (INN) in its pharmaceutical form, is a releasing hormone of growth hormone (GH). It is a 44-amino acid peptide hormone produced in the arcuate nucleus of the hypothalamus.

Sermorelin acetate, also known as GHRH (1-29), is a peptide analogue of growth hormone-releasing hormone (GHRH) which is used as a diagnostic agent to assess growth hormone (GH) secretion for the purpose of diagnosing growth hormone deficiency. It is a 29-amino acid polypeptide representing the 1–29 fragment from endogenous human GHRH, thought to be the shortest fully functional fragment of GHRH.

<span class="mw-page-title-main">GHRP-6</span> Chemical compound

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Lipoatrophy is the term describing the localized loss of fat tissue. This may occur as a result of subcutaneous injections of insulin in the treatment of diabetes, from the use of human growth hormone or from subcutaneous injections of copaxone used for the treatment of multiple sclerosis. In the latter case, an injection may produce a small dent at the injection site. Lipoatrophy occurs in HIV-associated lipodystrophy, one cause of which is an adverse drug reaction that is associated with some antiretroviral medications.

<span class="mw-page-title-main">Growth-hormone-releasing hormone receptor</span> Receptor protein that binds with somatcrinin

The growth-hormone-releasing hormone receptor (GHRHR) is a G-protein-coupled receptor that binds growth hormone-releasing hormone. The GHRHR activates a Gs protein that causes a cascade of cAMP via adenylate cyclase. GHRHR is distinct from the growth hormone secretagogue receptor, where growth hormone releasing peptides act to release growth hormone.

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<span class="mw-page-title-main">Acromegaly</span> Human disease that results in excess growth of certain parts of the body

Acromegaly is a disorder that results in excess growth of certain parts of the human body. It is caused by excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. There may also be an enlargement of the forehead, jaw, and nose. Other symptoms may include joint pain, thicker skin, deepening of the voice, headaches, and problems with vision. Complications of the disease may include type 2 diabetes, sleep apnea, and high blood pressure.

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Growth hormone secretagogues or GH secretagogues (GHSs) are a class of drugs which act as secretagogues of growth hormone (GH). They include agonists of the ghrelin/growth hormone secretagogue receptor (GHSR), such as ghrelin (lenomorelin), pralmorelin (GHRP-2), GHRP-6, examorelin (hexarelin), ipamorelin, and ibutamoren (MK-677), and agonists of the growth hormone-releasing hormone receptor (GHRHR), such as growth hormone-releasing hormone, CJC-1295, sermorelin, and tesamorelin.

<span class="mw-page-title-main">Pralmorelin</span> Chemical compound

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<span class="mw-page-title-main">Ipamorelin</span> Peptide selective agonist of the ghrelin/growth hormone secretagogue receptor

Ipamorelin (INN) (developmental code name NNC 26-0161) is a peptide selective agonist of the ghrelin/growth hormone secretagogue receptor (GHS) and a growth hormone secretagogue. It is a pentapeptide with the amino acid sequence Aib-His-D-2-Nal-D-Phe-Lys-NH2 that was derived from GHRP-1.

<span class="mw-page-title-main">Examorelin</span> Chemical compound

Examorelin (INN) (developmental code names EP-23905, MF-6003), also known as hexarelin, is a potent, synthetic, peptidic, orally-active, centrally-penetrant, and highly selective agonist of the ghrelin/growth hormone secretagogue receptor (GHSR) and a growth hormone secretagogue which was developed by Mediolanum Farmaceutici. It is a hexapeptide with the amino acid sequence His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2 which was derived from GHRP-6. These GH-releasing peptides have no sequence similarity to ghrelin, but mimic ghrelin by acting as agonists at the ghrelin receptor.

References

  1. ↑ "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.
  2. ↑ "FDA Application Chemistry Review" (PDF).
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ DeRuiter J, Holston PL. "Review of Selected NMEs 2011". www.uspharmacist.com. Auburn: Health Information Designs, Inc. Retrieved 2019-06-22.
  8. ↑ 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.
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