Capromorelin

Capromorelin
Clinical data
ATC code	none;
Pharmacokinetic data
Elimination half-life	2.4 hours
Identifiers
	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;
CAS Number	193273-66-4 ;
PubChem CID	216208;
ChemSpider	187411 ;
UNII	0MQ44VUN84;
ChEMBL	ChEMBL113313 ;
CompTox Dashboard (EPA)	DTXSID5057886 ;
Chemical and physical data
Formula	C28H35N5O4
Molar mass	505.619 g·mol−1
3D model (JSmol)	Interactive image;
	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;
	InChI InChI=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 ; Key:KVLLHLWBPNCVNR-SKCUWOTOSA-N ;
	(verify)

Capromorelin (INN) (developmental code name CP-424,391) is an investigational medication developed by the Pfizer drug company.^[2]^[3] It 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. Initial studies have shown the drug to directly raise insulin growth factor 1 (IGF-1) and growth hormone levels.^[4]

The drug is being considered for its therapeutic value in aging adults because elderly people have much lower levels of growth hormone and less lean muscle mass, which can result in weakness and frailty.^[5]

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 2nd planned year.^[6]

As of 2017, Capromorelin studies in humans had been discontinued.^[7]^[8]

References

^ Khojasteh-Bakht SC, O'donnell JP, Fouda HG, Potchoiba MJ (January 2005). "Metabolism, pharmacokinetics, tissue distribution, and excretion of [14C]CP-424391 in rats". Drug Metabolism and Disposition. 33 (1): 190–9. doi:10.1124/dmd.104.001065. PMID 15486077.
^ Carpino PA, Lefker BA, Toler SM, Pan LC, Hadcock JR, Murray MC, et al. (November 2002). "Discovery and biological characterization of capromorelin analogues with extended half-lives". Bioorganic & Medicinal Chemistry Letters. 12 (22): 3279–82. doi:10.1016/s0960-894x(02)00734-5. PMID 12392732.
^ Carpino PA, Lefker BA, Toler SM, Pan LC, Hadcock JR, Cook ER, et al. (February 2003). "Pyrazolinone-piperidine dipeptide growth hormone secretagogues (GHSs). Discovery of capromorelin". Bioorganic & Medicinal Chemistry. 11 (4): 581–90. doi:10.1016/s0968-0896(02)00433-9. PMID 12538023.
^ Pan LC, Carpino PA, Lefker BA, Ragan JA, Toler SM, Pettersen JC, et al. (February 2001). "Preclinical pharmacology of CP-424,391, an orally active pyrazolinone-piperidine [correction of pyrazolidinone-piperidine] growth hormone secretagogue". Endocrine. 14 (1): 121–32. doi:10.1385/ENDO:14:1:121. PMID 11322494.
^ Thompson DD (2007). "Aging and sarcopenia". Journal of Musculoskeletal & Neuronal Interactions. 7 (4): 344–5. PMID 18094505.
^ White HK, Petrie CD, Landschulz W, MacLean D, Taylor A, Lyles K, et al. (April 2009). "Effects of an oral growth hormone secretagogue in older adults". The Journal of Clinical Endocrinology and Metabolism. 94 (4): 1198–206. doi:10.1210/jc.2008-0632. PMID 19174493.
^ Rhodes, Linda; Zollers, Bill; Wofford, Jessica A.; Heinen, Ernst (February 2018). "Capromorelin: a ghrelin receptor agonist and novel therapy for stimulation of appetite in dogs". Veterinary Medicine and Science. 4 (1): 3–16. doi:10.1002/vms3.83.
^ Linda Rhodes, Bill Zollers, Jessica A. Wofford, and Ernst Heinen (2018). "Capromorelin: a ghrelin receptor agonist and novel therapy for stimulation of appetite in dogs". Vet Med Sci. PMID 29468076.

Researchers

Pfizer
Merck
University of Washington/VA Puget Sound Health Care System: Dr. George Merriam
University of Poland: Dr. Agnieszka Baranowska-Bik

External links

Clinical Trials

[1] Khojasteh-Bakht SC, O'donnell JP, Fouda HG, Potchoiba MJ (January 2005). "Metabolism, pharmacokinetics, tissue distribution, and excretion of [14C]CP-424391 in rats". Drug Metabolism and Disposition. 33 (1): 190–9. doi:10.1124/dmd.104.001065. PMID 15486077.

[2] Carpino PA, Lefker BA, Toler SM, Pan LC, Hadcock JR, Murray MC, et al. (November 2002). "Discovery and biological characterization of capromorelin analogues with extended half-lives". Bioorganic & Medicinal Chemistry Letters. 12 (22): 3279–82. doi:10.1016/s0960-894x(02)00734-5. PMID 12392732.

[3] Carpino PA, Lefker BA, Toler SM, Pan LC, Hadcock JR, Cook ER, et al. (February 2003). "Pyrazolinone-piperidine dipeptide growth hormone secretagogues (GHSs). Discovery of capromorelin". Bioorganic & Medicinal Chemistry. 11 (4): 581–90. doi:10.1016/s0968-0896(02)00433-9. PMID 12538023.

[4] Pan LC, Carpino PA, Lefker BA, Ragan JA, Toler SM, Pettersen JC, et al. (February 2001). "Preclinical pharmacology of CP-424,391, an orally active pyrazolinone-piperidine [correction of pyrazolidinone-piperidine] growth hormone secretagogue". Endocrine. 14 (1): 121–32. doi:10.1385/ENDO:14:1:121. PMID 11322494.

[5] Thompson DD (2007). "Aging and sarcopenia". Journal of Musculoskeletal & Neuronal Interactions. 7 (4): 344–5. PMID 18094505.

[6] White HK, Petrie CD, Landschulz W, MacLean D, Taylor A, Lyles K, et al. (April 2009). "Effects of an oral growth hormone secretagogue in older adults". The Journal of Clinical Endocrinology and Metabolism. 94 (4): 1198–206. doi:10.1210/jc.2008-0632. PMID 19174493.

[7] Rhodes, Linda; Zollers, Bill; Wofford, Jessica A.; Heinen, Ernst (February 2018). "Capromorelin: a ghrelin receptor agonist and novel therapy for stimulation of appetite in dogs". Veterinary Medicine and Science. 4 (1): 3–16. doi:10.1002/vms3.83.

[capromorelin-8] Linda Rhodes, Bill Zollers, Jessica A. Wofford, and Ernst Heinen (2018). "Capromorelin: a ghrelin receptor agonist and novel therapy for stimulation of appetite in dogs". Vet Med Sci. PMID 29468076.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

Clinical data

ATC code	none
Pharmacokinetic data
Elimination half-life	2.4 hours^[1]
Identifiers
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
CAS Number	193273-66-4
PubChem CID	216208
ChemSpider	187411
UNII	0MQ44VUN84
ChEMBL	ChEMBL113313
CompTox Dashboard (EPA)	DTXSID5057886
Chemical and physical data
Formula	C₂₈H₃₅N₅O₄
Molar mass	505.619 g·mol⁻¹
3D model (JSmol)	Interactive image
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
InChI InChI=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 Key:KVLLHLWBPNCVNR-SKCUWOTOSA-N
(verify)

Capromorelin

See also

References

Researchers

External links