"目录号: HY-14734A
GPCR/G Protein-
Anamorelin(RC1291; ONO-7643)是口服活性的饥饿素受体（ghrelin receptor）激动剂。
GHSR
相关产品
Anamorelin-Ibutamoren Mesylate-Alexamorelin-AZP-531-GHRP-2 metabolite 1-Capromorelin Tartrate-Examorelin-TC-G-1008-
生物活性
Description
Anamorelin hydrochloride is a novelghrelin receptoragonist withEC50value of 0.74 nM in the FLIPR assay.
IC50& Target
Ki: 0.7 nM (ghrelin receptor)[1]
EC50: 0.74 nM (ghrelin receptor)[1]
In Vitro
In the FLIPR assay, Anamorelin (ANAM) shows significant agonist activity on the ghrelin receptor, with EC50value of 0.74 nM. No significant antagonist activity is observed with Anamorelin at concentrations of up to 1,000 nM. In the binding experiments, Anamorelin binds to the ghrelin receptor with a binding affinity constant (Ki) of 0.70 nM. In the competition assay with radiolabeled ibutamoren (35S-MK-677; another ghrelin receptor agonist) Anamorelin (ANAM) is also found to bind with high affinity to the ghrelin receptor (IC50=0.69 nM). In rat pituitary cells incubated with Anamorelin, there is a dose-dependent stimulatory effect on GH release and the potency (EC50) is 1.5 nM. Anamorelin is screened for activity against a set of over 100 receptors, ion channels, transporters, and enzymes. Anamorelin demonstrates binding to the tachykinin neurokinin 2 (NK2) site (IC50=0.021 μM); however, a subsequent NK2functional assay demonstrates no functional activity[1].?
In Vivo
In rats, Anamorelin (ANAM) at an oral dose of 3, 10, or 30 mg/kg once daily significantly increases both food intake and body weight from Day 2 to Day 7 of treatment compared with the vehicle control. The cumulative change in food intake and weight gain increases dose-dependently, and these changes are significant at all dose levels (P<0.05) compared to the control. Administration of Anamorelin at a single oral dose of 3, 10, or 30 mg/kg induces a dose-dependent increase in plasma GH levels and GH AUC0-6hin rats[1].
Clinical Trial
NCT03035409
M.D. Anderson Cancer Center-Helsinn Healthcare SA
Malignant Neoplasms of Independent (Primary) Multiple Sites-Advanced Cancer-Metastatic or Recurrent Incurable Solid Tumors
February 8, 2017
Phase 2
NCT01387269
Helsinn Therapeutics (U.S.), Inc
Cachexia-Non-Small Cell Lung Cancer
July 2011
Phase 3
NCT01387282
Helsinn Therapeutics (U.S.), Inc
Cachexia-Non-Small Cell Lung Cancer
July 2011
Phase 3
NCT01395914
Helsinn Therapeutics (U.S.), Inc
Cachexia-Non-Small Cell Lung Cancer
July 2011
Phase 3
NCT00622193
Helsinn Therapeutics (U.S.), Inc
Carcinoma, Non-Small-Cell Lung
March 2008
Phase 2
NCT01505764
VA Office of Research and Development-Helsinn Therapeutics (U.S.), Inc
Cancer Cachexia
June 2012
Phase 2
NCT03035409
M.D. Anderson Cancer Center-Helsinn Healthcare SA
Malignant Neoplasms of Independent (Primary) Multiple Sites-Advanced Cancer-Metastatic or Recurrent Incurable Solid Tumors
February 8, 2017
Phase 2
NCT01387269
Helsinn Therapeutics (U.S.), Inc
Cachexia-Non-Small Cell Lung Cancer
July 2011
Phase 3
NCT01387282
Helsinn Therapeutics (U.S.), Inc
Cachexia-Non-Small Cell Lung Cancer
July 2011
Phase 3
NCT01395914
Helsinn Therapeutics (U.S.), Inc
Cachexia-Non-Small Cell Lung Cancer
July 2011
Phase 3
NCT00622193
Helsinn Therapeutics (U.S.), Inc
Carcinoma, Non-Small-Cell Lung
March 2008
Phase 2
NCT01505764
VA Office of Research and Development-Helsinn Therapeutics (U.S.), Inc
Cancer Cachexia
June 2012
Phase 2
NCT00378131
Helsinn Therapeutics (U.S.), Inc
Cancer Cachexia
September 2006
Phase 2
NCT00267358
Helsinn Therapeutics (U.S.), Inc
Cancer Cachexia
November 2005
Phase 2
NCT00219817
Helsinn Therapeutics (U.S.), Inc
Cancer Cachexia
June 2005
Phase 2
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References
[1].Pietra C, et al. Anamorelin HCl (ONO-7643), a novel ghrelin receptor agonist, for the treatment of cancer anorexia-cachexiasyndrome: preclinical profile. J Cachexia Sarcopenia Muscle. 2014 Dec;5(4):329-37.