PF-5190457 is a novel, potent, orally available and selective ghrelin receptor inverse agonist with a pKi of 8.36. PF-5190457 stimulates human islets with glucose to effectively increase insulin secretion. The ghrelin receptor pharmacology and off-target selectivity of PF-5190457 are better balanced. Clinical trials involving humans were initiated for PF-5190457 due to its encouraging safety and pharmacological profile.
Physicochemical Properties
| Molecular Formula | C29H32N6OS |
| Molecular Weight | 512.668984413147 |
| Exact Mass | 512.235 |
| Elemental Analysis | C, 67.94; H, 6.29; N, 16.39; O, 3.12; S, 6.25 |
| CAS # | 1334782-79-4 |
| PubChem CID | 58438464 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.4±0.1 g/cm3 |
| Index of Refraction | 1.757 |
| LogP | 4.8 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 37 |
| Complexity | 842 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | S1C(C)=CN2C1=NC(=C2)CC(N1CCC2(CC1)CN([C@H]1C3C=CC(C4C=C(C)N=CN=4)=CC=3CC1)C2)=O |
| InChi Key | ZIUDADZJCKGWKR-AREMUKBSSA-N |
| InChi Code | InChI=1S/C29H32N6OS/c1-19-11-25(31-18-30-19)22-3-5-24-21(12-22)4-6-26(24)35-16-29(17-35)7-9-33(10-8-29)27(36)13-23-15-34-14-20(2)37-28(34)32-23/h3,5,11-12,14-15,18,26H,4,6-10,13,16-17H2,1-2H3/t26-/m1/s1 |
| Chemical Name | 2-(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)-1-[2-[(1R)-5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonan-7-yl]ethanone |
| Synonyms | PF5190457; PF-05190457; PF-5190457; PF 5190457; PF05190457; PF 05190457 |
| 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 |
| 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
| Targets | Humnan ghrelin receptor ( pKi = 8.36 ) |
| ln Vitro | PF-5190457 possesses an optimal ratio between off-target selectivity and ghrelin receptor pharmacology[1]. |
| ln Vivo | PF-5190457 has strong increases in glucose-stimulated insulin secretion in human whole and dispersed islets, along with excellent selectivity[1]. |
| References |
[1]. Discovery of PF-5190457, a Potent, Selective, and Orally Bioavailable Ghrelin Receptor Inverse Agonist Clinical Candidate. ACS Med Chem Lett. 2014 Feb 24;5(5):474-9. |
| Additional Infomation | PF-5190457 is under investigation in clinical trial NCT01522807 (A Study Of Three PF-05190457 Formulations In Healthy Volunteers). |
Solubility Data
| Solubility (In Vitro) |
DMSO: ~250 mg/mL (~487.6 mM) Ethanol: ~100 mg/mL (~195.1 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.88 mM) (saturation unknown) in 10% EtOH + 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 EtOH 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 (4.88 mM) (saturation unknown) in 10% EtOH + 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 EtOH 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 (4.88 mM) (saturation unknown) in 10% EtOH + 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 EtOH stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: ≥ 2.08 mg/mL (4.06 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 20.8 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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 5: ≥ 2.08 mg/mL (4.06 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9506 mL | 9.7529 mL | 19.5057 mL | |
| 5 mM | 0.3901 mL | 1.9506 mL | 3.9011 mL | |
| 10 mM | 0.1951 mL | 0.9753 mL | 1.9506 mL |