G-5555 |
| Catalog No.GC18720 |
G-5555는 PAK1 및 PAK2에 대해 각각 3.7nM 및 11nM의 Kis를 갖는 강력한 p21 활성화 키나제 1(PAK1) 억제제입니다.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1648863-90-4
Sample solution is provided at 25 µL, 10mM.
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G-5555 is a potent p21-activated kinase 1 (PAK1) inhibitor with Kis of 3.7 nM and 11 nM for PAK1 and PAK2, respectively.
G-5555 is a potent PAK1 inhibitor with a Ki of 3.7 nM. G-5555 shows excellent kinase selectivity and inhibits only eight out of the 235 kinases tested other than PAK1 with inhibition >70%: PAK2, PAK3, KHS1, Lck, MST3, MST4, SIK2, and YSK1. The IC50s of G-5555 against SIK2, PAK2, KHS1, MST4, YSK1, MST3 and Lck are 9, 11, 10, 20, 34, 43, 52 nM, respectively. In general, G-5555 demonstrates high selectivity for the group I PAKs. There is negligible activity for G-5555 against the hERG channel with IC50 more than 10 μM in a patch clamp assay[1]. G-5555 potently inhibits PAK2, with a Ki of 11 nM. In an array of 23 breast cancer cell lines, G-5555 has significantly greater growth inhibitory activity in cell lines that are PAK-amplified compared to non-amplified lines[2].
G-5555 exhibits low blood clearance and an acceptable half-life. Good oral exposure (AUC = 30 μM•h) and high oral bioavailability (F = 80%) are achieved[1]. In an H292 non-small cell lunger cancer (NSCLC) xenograft study in mice, G-5555 inhibits phosphorylation of the PAK1/2 downstream substrate mitogen-activated protein kinase 1 (MEK1) S298 and, when administered at an oral dose of 25 mg/kg b.i.d., imparts 60% tumor growth inhibition in this model13 and a PAK1 amplified breast cancer xenograft model, MDAMB-175[2].
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.
Kinase experiment: | The 10 ?L assay mixtures contain 50 mM HEPES (pH 7.5), 0.01% Brij-35, 10 mM MgCl2, 1 mM EGTA, 2 ?M FRET peptide substrate, and PAK enzyme (20 pM PAK1; 50 pM PAK2; 90 pM PAK4). Incubations are carried out at 22°C in black polypropylene 384-well plates. Prior to the assay, enzyme, FRET peptide substrate and serially diluted test compounds (G-5555, etc.) are preincubated together in assay buffer (7.5 ?L) for 10 minutes, and the assay is initiated by the addition of 2.5 ?L assay buffer containing 4× ATP (160 ?M PAK1; 480 ?M PAK2; 16 ?M PAK4). Following the 60-minute incubation, the assay mixtures are quenched by the addition of development reagent, and 1 hour later the emissions of Coumarin (445 nm) and Fluorescein (520 nm) are determined after excitation at 400 nm[1]. |
Animal experiment: | Mice[1]Three mice in each of the two groups are administered 25 mg/kg oral suspension dose twice, with the second dose given 6 hours after the first dose. The dose volumes are 5 mL/kg for the IV group and 10 mL/kg for the PO groups. Following administration of G-5555, 15 ?L of blood is collected at each time point are stored at -70 to -80°C until analysis[1]. |
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. | |
| Cas No. | 1648863-90-4 | SDF | |
| Chemical Name | 8-[(trans-5-amino-1,3-dioxan-2-yl)methyl]-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-(methylamino)-pyrido[2,3-d]pyrimidin-7(8H)-one | ||
| Canonical SMILES | CNC1=NC=C(C=C(C2=C(Cl)C=C(C3=NC(C)=CC=C3)C=C2)C(N4C[C@@H]5OC[C@@H](N)CO5)=O)C4=N1 | ||
| Formula | C25H25ClN6O3 | M.Wt | 493 |
| Solubility | DMSO : ≥ 170 mg/mL (321.11 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.0284 mL | 10.142 mL | 20.284 mL |
| 5 mM | 0.4057 mL | 2.0284 mL | 4.0568 mL |
| 10 mM | 0.2028 mL | 1.0142 mL | 2.0284 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 16 reference(s) in Google Scholar.)
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