"目錄號(hào): HY-14734A

GPCR/G Protein-

Anamorelin(RC1291; ONO-7643)是口服活性的饑餓素受體（ghrelin receptor）激動(dòng)劑检访。

GHSR

相關(guān)產(chǎn)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.