| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
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| Targets |
PAK1 3.7 nM (Ki) PAK2 11 nM (Ki)
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|---|---|
| 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].
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| 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].
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| References |
[1]. Ndubaku CO, et al. 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]. Rudolph J, et al. 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. |
| Molecular Formula |
C25H26CL2N6O3
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|---|---|
| Molecular Weight |
529.42
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| Related CAS # |
G-5555;1648863-90-4
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| 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 |
*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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