capromorelin
{{Short description|Chemical compound}}
{{Use dmy dates|date=December 2022}}
{{Unbalanced|date=March 2017}}
{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 464366037
| image = Capromorelin skeletal.svg
| alt =
| pronounce =
| tradename = Entyce, Elura, Eluracat
| Drugs.com =
| MedlinePlus =
| DailyMedID = Capromorelin
| pregnancy_AU =
| pregnancy_AU_comment =
| pregnancy_category =
| routes_of_administration = By mouth
| class =
| ATCvet = yes
| ATC_prefix = H01
| ATC_suffix = AX90
| ATC_supplemental =
| legal_AU =
| legal_AU_comment =
| legal_BR =
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment = {{cite web | title=Notice: Multiple additions to the Prescription Drug List (PDL) [2024-08-13] | website=Health Canada | date=13 August 2024 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/prescription-drug-list/notices-changes/multiple-additions-2024-08-13.html | access-date=15 August 2024}}
| legal_DE =
| legal_DE_comment =
| legal_NZ =
| legal_NZ_comment =
| legal_UK =
| legal_UK_comment =
| legal_US = Rx-only
| legal_EU = Rx-only
| legal_EU_comment = {{cite web | website=European Medicines Agency | title=Eluracat EPAR | date=22 May 2023 | url=https://www.ema.europa.eu/en/medicines/veterinary/EPAR/eluracat | access-date=24 May 2024}}
| legal_UN =
| legal_UN_comment =
| legal_status =
| bioavailability =
| protein_bound =
| metabolism =
| metabolites =
| onset =
| duration_of_action =
| excretion =
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 193273-66-4
| PubChem = 216208
| IUPHAR_ligand =
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB15205
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 187411
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 0MQ44VUN84
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| KEGG = D03373
| ChEBI =
| ChEMBL = 113313
| NIAID_ChemDB =
| PDB_ligand =
| synonyms = CP-424,391
| IUPAC_name = N-[(2R)-1-[(3aR)-2-methyl-3-oxo-3a-(phenylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl]-1-oxo-3-(phenylmethoxy)propan-2-yl]-2-amino-2-methylpropanamide
| C=28 | H=35 | N=5 | O=4
| smiles = CC(C)(C(=O)N[C@H](COCC1=CC=CC=C1)C(=O)N2CCC3=NN(C(=O)[C@@]3(C2)CC4=CC=CC=C4)C)N
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C28H35N5O4/c1-27(2,29)25(35)30-22(18-37-17-21-12-8-5-9-13-21)24(34)33-15-14-23-28(19-33,26(36)32(3)31-23)16-20-10-6-4-7-11-20/h4-13,22H,14-19,29H2,1-3H3,(H,30,35)/t22-,28-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = KVLLHLWBPNCVNR-SKCUWOTOSA-N
}}
Capromorelin, sold under the brand names Entyce and Elura, is a medication used for the management of weight loss in cats and dogs.{{cite web | title=Entyce | website=U.S. Food and Drug Administration (FDA) | url=https://animaldrugsatfda.fda.gov/adafda/views/#/home/previewsearch/141-457 | access-date=12 December 2022}}{{cite web | title=Elura | website=U.S. Food and Drug Administration (FDA) | url=https://animaldrugsatfda.fda.gov/adafda/views/#/home/previewsearch/141-536 | access-date=12 December 2022}} Capromorelin is a ghrelin receptor agonist known to increase appetite and weight gain.
Capromorelin was developed by Pfizer.{{cite journal | vauthors = Carpino PA, Lefker BA, Toler SM, Pan LC, Hadcock JR, Murray MC, Cook ER, DiBrino JN, DeNinno SL, Chidsey-Frink KL, Hada WA, Inthavongsay J, Lewis SK, Mangano FM, Mullins MA, Nickerson DF, Ng O, Pirie CM, Ragan JA, Rose CR, Tess DA, Wright AS, Yu L, Zawistoski MP, Pettersen JC, DaSilva-Jardine PA, Wilson TC, Thompson DD | display-authors = 6 | title = Discovery and biological characterization of capromorelin analogues with extended half-lives | journal = Bioorganic & Medicinal Chemistry Letters | volume = 12 | issue = 22 | pages = 3279–82 | date = November 2002 | pmid = 12392732 | doi = 10.1016/s0960-894x(02)00734-5 }}{{cite journal | vauthors = Carpino PA, Lefker BA, Toler SM, Pan LC, Hadcock JR, Cook ER, DiBrino JN, Campeta AM, DeNinno SL, Chidsey-Frink KL, Hada WA, Inthavongsay J, Mangano FM, Mullins MA, Nickerson DF, Ng O, Pirie CM, Ragan JA, Rose CR, Tess DA, Wright AS, Yu L, Zawistoski MP, DaSilva-Jardine PA, Wilson TC, Thompson DD | display-authors = 6 | title = Pyrazolinone-piperidine dipeptide growth hormone secretagogues (GHSs). Discovery of capromorelin | journal = Bioorganic & Medicinal Chemistry | volume = 11 | issue = 4 | pages = 581–90 | date = February 2003 | pmid = 12538023 | doi = 10.1016/s0968-0896(02)00433-9 }}
Capromorelin was approved for veterinary use in the United States in May 2016.{{cite web | title=Aratana Therapeutics Granted FDA Approval of Entyce (capromorelin oral solution) | publisher=Aratana Therapeutics | via=PR Newswire | date=17 May 2016 | url=https://www.prnewswire.com/news-releases/aratana-therapeutics-granted-fda-approval-of-entyce-capromorelin-oral-solution-300270460.html | access-date=12 December 2022}} It is the second drug approved for the management of weight loss in cats and the first drug approved specifically for the management of weight loss in cats with chronic kidney disease.
Research
Capromorelin functions to stimulate the secretion of growth hormone and as a ghrelin mimetic which causes the body to secrete human growth hormone in a way usually seen at puberty and in young adulthood. Studies have shown the drug to directly raise insulin growth factor 1 (IGF-1) and growth hormone levels.{{cite journal | vauthors = Pan LC, Carpino PA, Lefker BA, Ragan JA, Toler SM, Pettersen JC, Nettleton DO, Ng O, Pirie CM, Chidsey-Frink K, Lu B, Nickerson DF, Tess DA, Mullins MA, MacLean DB, DaSilva-Jardine PA, Thompson DD | display-authors = 6 | title = Preclinical pharmacology of CP-424,391, an orally active pyrazolinone-piperidine [correction of pyrazolidinone-piperidine] growth hormone secretagogue | journal = Endocrine | volume = 14 | issue = 1 | pages = 121–32 | date = February 2001 | pmid = 11322494 | doi = 10.1385/ENDO:14:1:121 | s2cid = 46978604 }}
In a one-year treatment trial (starting 1999) with 395 seniors between 65 and 84 years old, patients who received the drug gained an average of 3 lb (1.4 kg) in lean body mass in the first six months and also were better able to walk in a straight line in a test of balance, strength and coordination. After 12 months, patients receiving capromorelin also had an improved ability to climb stairs; however, the results were not good enough to continue the trial for the second planned year.{{cite journal | vauthors = White HK, Petrie CD, Landschulz W, MacLean D, Taylor A, Lyles K, Wei JY, Hoffman AR, Salvatori R, Ettinger MP, Morey MC, Blackman MR, Merriam GR | display-authors = 6 | title = Effects of an oral growth hormone secretagogue in older adults | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 94 | issue = 4 | pages = 1198–206 | date = April 2009 | pmid = 19174493 | doi = 10.1210/jc.2008-0632 | doi-access = free }}
As of 2017, capromorelin studies in humans had been discontinued.{{cite journal | vauthors = Rhodes L, Zollers B, Wofford JA, Heinen E | title = Capromorelin: a ghrelin receptor agonist and novel therapy for stimulation of appetite in dogs | journal = Veterinary Medicine and Science | volume = 4 | issue = 1 | pages = 3–16 | date = February 2018 | pmid = 29468076 | pmc = 5813110 | doi = 10.1002/vms3.83 }}
Veterinary uses
Capromorelin is indicated for the management of weight loss in cats and dogs.