GSK3004774 is a novel, potent, nonabsorbable agonist of CaSR, with an pEC50 of 7.3, 6.6 and 6.5 for human, mouse and rat CaSR, respectively. GSK3004774 shows an EC50 of 50 nM for human CaSR. Modulation of gastrointestinal nutrient sensing pathways provides a promising a new approach for the treatment of metabolic diseases including diabetes and obesity. The calcium-sensing receptor has been identified as a key receptor involved in mineral and amino acid nutrient sensing and thus is an attractive target for modulation in the intestine.
Physicochemical Properties
| Molecular Formula | C32H40N4O3 |
| Molecular Weight | 528.685008049011 |
| Exact Mass | 528.31 |
| CAS # | 2138814-32-9 |
| PubChem CID | 137628638 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 2.4 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 10 |
| Heavy Atom Count | 39 |
| Complexity | 792 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | OC(C1CCN(CCCNC(C2C=CC(=CC=2)N2CC[C@H](C2)N[C@@H](C)C2=CC=CC3C=CC=CC2=3)=O)CC1)=O |
| InChi Key | HBTVUVNVTSSIHP-KCWPFWIISA-N |
| InChi Code | InChI=1S/C32H40N4O3/c1-23(29-9-4-7-24-6-2-3-8-30(24)29)34-27-16-21-36(22-27)28-12-10-25(11-13-28)31(37)33-17-5-18-35-19-14-26(15-20-35)32(38)39/h2-4,6-13,23,26-27,34H,5,14-22H2,1H3,(H,33,37)(H,38,39)/t23-,27+/m1/s1 |
| Chemical Name | 1-[3-[[4-[(3S)-3-[[(1R)-1-naphthalen-1-ylethyl]amino]pyrrolidin-1-yl]benzoyl]amino]propyl]piperidine-4-carboxylic acid |
| Synonyms | GSK-3004774; GSK3004774; GSK 3004774 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| References |
[1]. Identification of potent, nonabsorbable agonists of the calcium-sensing receptor for GI-specific administration. Bioorg Med Chem Lett. 2017 Oct 15;27(20):4673-4677. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~189.15 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.73 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (4.73 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8915 mL | 9.4573 mL | 18.9147 mL | |
| 5 mM | 0.3783 mL | 1.8915 mL | 3.7829 mL | |
| 10 mM | 0.1891 mL | 0.9457 mL | 1.8915 mL |