Anamorelin hydrochloride

• CAT Number: I002354
• CAS Number: 861998-00-7
• Molecular Formula: C31H43ClN6O3
• Molecular Weight: 583.16
• Purity: ≥95%
• Target: GHSR
• Solubility: Soluble in water
• Storage: 0 - 4°Cfor short term (days to weeks), or -20 °C for long term (months).
• IUPAC Name: 2-amino-N-[(2R)-1-[(3R)-3-benzyl-3-[dimethylamino(methyl)carbamoyl]piperidin-1-yl]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2-methylpropanamide;hydrochloride
• InChI: InChI=1S/C31H42N6O3.ClH/c1-30(2,32)28(39)34-26(18-23-20-33-25-15-10-9-14-24(23)25)27(38)37-17-11-16-31(21-37,29(40)36(5)35(3)4)19-22-12-7-6-8-13-22;/h6-10,12-15,20,26,33H,11,16-19,21,32H2,1-5H3,(H,34,39);1H/t26-,31-;/m1./s1
• InChIKey: VFYAEUWJFGTGGO-GHTUPXNNSA-N
• SMILES: CC(C)(N)C(N[C@H](CC1=CNC2=C1C=CC=C2)C(N3C[C@](C(N(C)N(C)C)=O)(CC4=CC=CC=C4)CCC3)=O)=O.[H]Cl.

Anamorelin (Cat.No:I002354), also known as RC-1291 or ONO-7643, is the orally bioavailable, small-molecule ghrelin mimetic with appetite-stimulating and anabolic activities. Anamorelin binds to and stimulates the growth hormone secretagogue receptor (GHSR) centrally, thereby mimicking the appetite-stimulating and growth hormone-releasing effects of grhelin. Stimulation of GHSR may also reduce the production of the pro-inflammatory cytokines TNF-alpha and interleukin-6, which may play a direct role in cancer-related loss of appetite.

Reference

1:J Cachexia Sarcopenia Muscle. 2014 Dec;5(4):329-37. doi: 10.1007/s13539-014-0159-5. Epub 2014 Sep 30. Anamorelin HCl (ONO-7643), a novel ghrelin receptor agonist, for the treatment of cancer anorexia-cachexia syndrome: preclinical profile.Pietra C,Takeda Y,Tazawa-Ogata N,Minami M,Yuanfeng X,Duus EM,Northrup R, PMID: 25267366 PMCID: PMC4248409 DOI: 10.1007/s13539-014-0159-5
Abstract: BACKGROUND: Anamorelin HCl (ANAM) is a novel, orally active, ghrelin receptor agonist in clinical development for the treatment of cancer cachexia. We report in vitro and in vivo studies evaluating the preclinical pharmacologic profile of ANAM.METHODS: Fluorescent imaging plate reader and binding assays in HEK293 and baby hamster kidney cells determined the agonist and antagonist activity of ANAM, and its affinity for the ghrelin receptor. Rat pituitary cells were incubated with ANAM to evaluate its effect on growth hormone (GH) release. In vivo, rats were treated with ANAM 3, 10, or 30 mg/kg, or control orally, once daily for 6 days to evaluate the effect on food intake (FI) and body weight (BW), and once to assess GH response. In pigs, single (3.5 mg/kg) or continuous (1 mg/kg/day) ANAM doses were administered to assess GH and insulin-like growth factor (IGF-1) response.RESULTS: ANAM showed significant agonist and binding activity on the ghrelin receptor, and stimulated GH release in vitro. In rats, ANAM significantly and dose-dependently increased FI and BW at all dose levels compared with control, and significantly increased GH levels at 10 or 30 mg/kg doses. Increases in GH and IGF-1 levels were observed following ANAM administration in pigs.CONCLUSION: ANAM is a potent and highly specific ghrelin receptor agonist with significant appetite-enhancing activity, leading to increases in FI and BW, and a stimulatory effect on GH secretion. These results support the continued investigation of ANAM as a potential treatment of cancer anorexia-cachexia syndrome.