| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Targets |
Growth hormone secretagogue receptor type 1a (GHSR1a / ghrelin receptor). GSK1614343 is a cyclized ghrelin antagonist.
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| ln Vitro |
(αR,8aS)-GSK1614343 (0.1-1μM) shows surmountable competitive antagonism against hGHSR1a with an average p KB value of 8.06[1].
GSK1614343 is a cyclized ghrelin antagonist with a pIC50 value of 8.4. It shows competitive antagonism of hGHSR1a with a mean pKb value of 8.06. GSK1614343 inhibits ghrelin-induced calcium mobilization and inositol phosphate accumulation in vitro. The compound has a pIC50 of 7.90 for inhibition of the calcium response induced by ghrelin. GSK1614343 demonstrates potent antagonist activity at the ghrelin receptor. |
| ln Vivo |
(αR,8aS)-GSK1614343 (10 mg/kg; intravenously administered once) suppresses the release of growth hormone (GH) when ghrelin is present [1]. The intravenous and oral form of (αR,8aS)-GSK1614343 has a suitable half-life (5.0 h), limited blood clearance (Clb=28 mL/min/kg), and good oral bioavailability (F=46%). After oral administration of the chemical at a dose of 3 mg/kg, a brain to blood AUC ratio of 2.2 was reported in terms of rat brain penetration [1]. With IC50 values less than 10 μM, (αR,8aS)-GSK1614343 exhibits a strong inhibitory ability against the main human CYP450 isoforms [1].
In vivo, GSK1614343 produces an unexpected increase of food intake and body weight in rodents and dogs. This is an unexpected effect for a ghrelin receptor antagonist, as ghrelin is known to stimulate appetite. The compound possesses a documented preclinical pharmacokinetic profile including brain penetration data, enabling its use in CNS-relevant studies. Specific dosing regimens and detailed efficacy data are available in the primary literature. |
| Enzyme Assay |
GHSR1a antagonist activity is assessed using in vitro calcium mobilization assays in cells expressing recombinant human GHSR1a. Cells are loaded with a fluorescent calcium indicator (e.g., Fluo-4 AM) and stimulated with ghrelin (typically 100 nM) in the presence of various concentrations of GSK1614343 (typically 0.001-100 μM). Intracellular calcium levels are measured using a fluorescence plate reader. Inositol phosphate accumulation is measured using radiolabeled inositol (e.g., [3H]-myo-inositol) or by ELISA-based IP1 assays. pIC50 and pKb values are calculated from dose-response curves using nonlinear regression analysis (e.g., Schild analysis for pKb determination).
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| Cell Assay |
Cellular activity is evaluated in cells expressing human GHSR1a (e.g., HEK293-GHSR1a stable cell lines). Cells are treated with GSK1614343 at various concentrations (typically 0.001-100 μM) for appropriate time periods (5-30 minutes for calcium assays, 30-60 minutes for IP accumulation). Ghrelin-induced calcium mobilization is measured using fluorescent calcium indicators. Inositol phosphate accumulation is measured using radiolabeled inositol or IP1 ELISA. Receptor binding affinity is assessed by radioligand binding assays using [125I]-ghrelin or other selective ligands. Selectivity is evaluated by testing against other GPCRs (e.g., GHSR1b, other peptide hormone receptors).
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| Animal Protocol |
In vivo efficacy is studied in rodents (mice, rats) and dogs. GSK1614343 is administered via various routes (oral, intravenous, intraperitoneal) at doses determined from pharmacokinetic studies. Food intake is measured by weighing food consumed over specific time periods (e.g., 1-24 hours post-dosing). Body weight is measured daily or weekly. Ghrelin-induced growth hormone secretion may be measured by collecting blood samples and measuring growth hormone levels by ELISA or radioimmunoassay. Brain penetration is assessed by measuring compound concentrations in brain tissue and plasma. Pharmacokinetic parameters including half-life (5.0 h), blood clearance (Clb = 28 mL/min/kg), and oral bioavailability (F = 46%) are determined. GSK1614343 (i.v. and p.o.) exhibits good oral bioavailability (F = 46%), a limited clearance in blood (Clb = 28 mL/min/kg), and a suitable half-life (5.0 h). Rat brain penetration data are available.
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| ADME/Pharmacokinetics |
(αR,8aS)-GSK1614343 has a molecular formula of C27H31N5O2 and a molecular weight of 457.57 g/mol. CAS Number: 1092476-84-0. It is a cyclized ghrelin antagonist. Purity: typically ≥98% by HPLC. The compound is soluble in DMSO and should be stored at -20°C for long-term stability, protected from light and moisture. The intravenous and oral form of (αR,8aS)-GSK1614343 has a suitable half-life (5.0 h), limited blood clearance (Clb = 28 mL/min/kg), and good oral bioavailability (F = 46%). Rat brain penetration data are available.
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| Toxicity/Toxicokinetics |
Safety data for GSK1614343 indicate it is a research compound for laboratory use only. As a ghrelin receptor antagonist with effects on food intake and body weight, it may have metabolic effects. Specific toxicological profiles including acute toxicity, organ toxicity, genotoxicity, and reproductive toxicity are not extensively published. Standard laboratory safety practices should be followed during handling, including the use of personal protective equipment and adequate ventilation. The compound is for research use only and not for human therapeutic applications without appropriate regulatory approval. Consult the material safety data sheet (MSDS) for detailed safety information.
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| References | |
| Additional Infomation |
GSK1614343 is a research tool compound for studying ghrelin receptor biology and appetite regulation. It is not approved for clinical use. The compound produces an unexpected increase of food intake and body weight in rodents and dogs, making it a valuable tool for understanding the complex biology of ghrelin signaling and its role in energy homeostasis. Unlike commonly cited comparators such as YIL-781 or PF-05190457 that lack systematic in vivo ADME characterization, (αR,8aS)-GSK1614343 possesses a documented preclinical pharmacokinetic profile including brain penetration data, enabling its use in CNS-relevant studies. Reference: (αR,8aS)-GSK1614343 (compound 18a, d2) is a cyclized ghrelin antagonist with a pIC50 value of 8.4.
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| Molecular Formula |
C22H23F6N5O
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| Molecular Weight |
487.44
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| Exact Mass |
487.18
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| CAS # |
1092476-84-0
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| Related CAS # |
GSK1614343;1092076-04-4
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| PubChem CID |
25124566
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| Appearance |
White to off-white solid powder
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
34
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| Complexity |
682
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| Defined Atom Stereocenter Count |
2
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| SMILES |
[C@H](C1=CN=CC=C1)(N1CCN2CCC[C@@]2([H])C1)C(=O)NNC1C=C(C(F)(F)F)C=C(C(F)(F)F)C=1
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| InChi Key |
QNOSCJDGJKVFJR-RTBURBONSA-N
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| InChi Code |
InChI=1S/C22H23F6N5O/c23-21(24,25)15-9-16(22(26,27)28)11-17(10-15)30-31-20(34)19(14-3-1-5-29-12-14)33-8-7-32-6-2-4-18(32)13-33/h1,3,5,9-12,18-19,30H,2,4,6-8,13H2,(H,31,34)/t18-,19-/m1/s1
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| Chemical Name |
(2R)-2-[(8aR)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl]-N'-[3,5-bis(trifluoromethyl)phenyl]-2-pyridin-3-ylacetohydrazide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~205.15 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0515 mL | 10.2577 mL | 20.5153 mL | |
| 5 mM | 0.4103 mL | 2.0515 mL | 4.1031 mL | |
| 10 mM | 0.2052 mL | 1.0258 mL | 2.0515 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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