Physicochemical Properties
| Molecular Formula | C25H26CL2N6O3 |
| Molecular Weight | 529.42 |
| CAS # | 2319590-15-1 |
| Related CAS # | G-5555;1648863-90-4 |
| Appearance | Light yellow to yellow solid powder |
| 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
| Targets | PAK1 3.7 nM (Ki) PAK2 11 nM (Ki) |
| ln Vitro | G-5555 demonstrates exceptional kinase selectivity, inhibiting only eight of the 235 kinases examined (excluding PAK1) with an inhibition level exceeding 70%: PAK2, PAK3, KHS1, Lck, MST3, MST4, SIK2, and YSK1. G-5555's IC50 values are 9, 11, 10, 20, 34, 43, and 52 nM for SIK2, PAK2, KHS1, MST4, YSK1, MST3, and Lck, respectively. G-5555 generally shows good selectivity for the group I PAKs. G-5555 exhibits very little action against the hERG channel in a patch clamp experiment, with an IC50 greater than 10 μM[1]. Across a range of 23 different breast cancer cell lines, G-5555 exhibits noticeably higher growth inhibitory efficacy in PAK-amplified lines as opposed to non-amplified cells[2]. |
| ln Vivo | G-5555 has a respectable half-life and minimal blood clearance. High oral bioavailability (F=80%) and good oral exposure (AUC=30 μM·h) are attained[1]. G-5555 inhibits phosphorylation of the PAK1/2 downstream substrate mitogen-activated protein kinase 1 (MEK1) S298 in an H292 non-small cell lung cancer (NSCLC) xenograft study in mice. When given orally at a dose of 25 mg/kg bid, this compound imparts 60% tumor growth inhibition in this model13, as well as in an amplified PAK1 breast cancer xenograft model, MDAMB-175[2]. |
| References |
[1]. Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-pK a Polar Moiety. ACS Med Chem Lett. 2015 Oct 31;6(12):1241-6. [2]. Chemically Diverse Group I p21-Activated Kinase (PAK) Inhibitors Impart Acute Cardiovascular Toxicity with a Narrow Therapeutic Window. J Med Chem. 2016 Jun 9;59(11):5520-41. |
Solubility Data
| Solubility (In Vitro) |
DMSO :~100 mg/mL (~188.89 mM) H2O :~16.67 mg/mL (~31.49 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.72 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 (4.72 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8889 mL | 9.4443 mL | 18.8886 mL | |
| 5 mM | 0.3778 mL | 1.8889 mL | 3.7777 mL | |
| 10 mM | 0.1889 mL | 0.9444 mL | 1.8889 mL |