1. Cell Cycle/DNA Damage
    Cytoskeleton
  2. PAK

G-5555 

Cat. No.: HY-19635 Purity: 99.18%
Handling Instructions

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.

For research use only. We do not sell to patients.
G-5555 Chemical Structure

G-5555 Chemical Structure

CAS No. : 1648863-90-4

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 119 In-stock
1 mg USD 70 In-stock
5 mg USD 110 In-stock
10 mg USD 160 In-stock
25 mg USD 360 In-stock
50 mg USD 640 In-stock
100 mg USD 1100 In-stock
200 mg   Get quote  
500 mg   Get quote  

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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

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.

IC50 & Target[2]

PAK1

3.7 nM (Ki)

PAK2

11 nM (Ki)

In Vitro

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].

In Vivo

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
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 2.0286 mL 10.1428 mL 20.2856 mL
5 mM 0.4057 mL 2.0286 mL 4.0571 mL
10 mM 0.2029 mL 1.0143 mL 2.0286 mL
Please refer to the solubility information to select the appropriate solvent.
Kinase Assay
[1]

The 10 µL assay mixtures contain 50 mM HEPES (pH 7.5), 0.01% Brij-35, 10 mM MgCl2, 1 mM EGTA, 2 µM 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 µL) for 10 minutes, and the assay is initiated by the addition of 2.5 µL assay buffer containing 4× ATP (160 µM PAK1; 480 µM PAK2; 16 µM 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].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

G-5555 is prepared in corn oil and MCT (0.5% (w/v) methylcellulose/0.2% (w/v) Tween 80 in sterile water[1].

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 µL of blood is collected at each time point are stored at -70 to -80°C until analysis[1].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

492.96

Formula

C₂₅H₂₅ClN₆O₃

CAS No.

1648863-90-4

SMILES

ClC(C=C(C1=NC(C)=CC=C1)C=C2)=C2C3=CC4=CN=C(NC)N=C4N(C[[email protected]@H]5OC[[email protected]@H](N)CO5)C3=O

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 27 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 99.18%

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Product Name:
G-5555
Cat. No.:
HY-19635
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