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Seralutinib (PK-10571; GB-002) is a novel and potent PDGFRα/β inhibitor used as an inhaled formulation for the treatment of PAH (pulmonary arterial hypertension). In a Su5416 Hypoxia Rat Model with PAH, seralutinib shows excellent in vivo efficacy.
Physicochemical Properties
| Molecular Formula | C27H27N5O3 |
| Molecular Weight | 469.545 |
| Exact Mass | 469.211 |
| Elemental Analysis | C, 69.07; H, 5.80; N, 14.92; O, 10.22 |
| CAS # | 1619931-27-9 |
| Related CAS # | 1619931-27-9 |
| PubChem CID | 91663352 |
| Appearance | White to light yellow solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 601.4±55.0 °C at 760 mmHg |
| Flash Point | 317.5±31.5 °C |
| Vapour Pressure | 0.0±1.7 mmHg at 25°C |
| Index of Refraction | 1.649 |
| LogP | 3.01 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 35 |
| Complexity | 667 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | O(C)C1=C(C=CC(=C1)C1=CN=CC(=N1)N[C@@H](C)C1C=CC=C(C=1)NC(C1C=NC=C(C)C=1)=O)OC |
| InChi Key | JHJNPOSPVGRIAN-SFHVURJKSA-N |
| InChi Code | InChI=1S/C27H27N5O3/c1-17-10-21(14-28-13-17)27(33)31-22-7-5-6-19(11-22)18(2)30-26-16-29-15-23(32-26)20-8-9-24(34-3)25(12-20)35-4/h5-16,18H,1-4H3,(H,30,32)(H,31,33)/t18-/m0/s1 |
| Chemical Name | N-[3-[(1S)-1-[[6-(3,4-dimethoxyphenyl)pyrazin-2-yl]amino]ethyl]phenyl]-5-methylpyridine-3-carboxamide |
| Synonyms | Seralutinib; PK-10571; GB002; PK10571; GB-002; PK 10571; GB 002 |
| 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 | CSF1R (IC50 = 8 nM); c-KIT (IC50 = 14 nM); PDGFRβ; PDGFRα |
| ln Vivo | Seralutinib (GB002) (treated respiratory, inhaled) significantly lowered right ventricular systolic pressure and mean pulmonary artery pressure. In Seralutinib (GB002)-treated mice, hemodynamic alterations were accompanied by reduced muscularization of pulmonary arterioles and lobar Seralutinib (GB002) was well tolerated [1]. GB002-mediated suppression of lung PDGFRα/β phosphorylation after adsorption to healthy Sprague Dawley [2]. Seralutinib is dose- and time-regulated. Induces lung BMPR2 protein expression [2]. |
| References |
[1]. Robert P. Frantz1, et.al. Phase 2 Clinical Study to Evaluate the Efficacy and Safety of Inhaled GB002 (Seralutinib) for the Treatment of World Health Organization Group 1 Pulmonary Arterial Hypertension. [2]. Abstract 11102: Gb002, A Novel Inhaled Pdgfr Kinase Inhibitor, Demonstrates Efficacy in the Su5416 Hypoxia Rat Model of Pulmonary Arterial Hypertension (pah). Circulation. 2019;140:A11102. [3]. Pharmacologic Characterization of GB002, a Novel Inhaled PDGFR Kinase Inhibitor in Development for Pulmonary Arterial Hypertension (PAH). |
Solubility Data
| Solubility (In Vitro) |
DMSO: 94~200 mg/mL (200.2~425.96 mM) Ethanol: ~94 mg/mL (~200.2 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5.75 mg/mL (12.25 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 57.5 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 2: ≥ 2.5 mg/mL (5.32 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 3: ≥ 2.5 mg/mL (5.32 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 | 2.1297 mL | 10.6485 mL | 21.2970 mL | |
| 5 mM | 0.4259 mL | 2.1297 mL | 4.2594 mL | |
| 10 mM | 0.2130 mL | 1.0648 mL | 2.1297 mL |