G-5555

SKU: orb1309653

Description

G-5555 is a potent and selective small molecule inhibitor of p21-activated kinase 1 (PAK1), with Kis of 3.7 nM and 11 nM for PAK1 and PAK2, respectively. This compound is a valuable research tool for studying PAK signaling in cancer cell proliferation, invasion, and metastasis in both in vitro and in vivo models.

Research Area

Signal Transduction

Key Properties

• CAS Number: 1648863-90-4
• MW: 492.96
• Purity: 99.70% (May vary between batches)
• Formula: C₂₅H₂₅ClN₆O₃
• SMILES: CNc1ncc2cc(-c3ccc(cc3Cl)-c3cccc(C)n3)c(=O)n(C[C@H]3OC[C@H](N)CO3)c2n1
• Target: PAK
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (2.03 mM);DMSO:1 mg/mL (2.03 mM)

Bioactivity

• Target IC50:
  PAK1:3.7 nM (ki)|PAK2:11 nM (ki)
• In Vivo:
  G-5555 has low blood clearance and an acceptable half-life. Good oral exposure (AUC = 30 μM h) and high oral bioavailability (F = 80%) are achieved. G-5555 inhibits phosphorylation of the PAK1/2 downstream substrate mitogen-activated protein kinase 1 (MEK1) S298, in an H292 non-small cell lunger cancer (NSCLC) xenograft study in mice. 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.
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• In Vitro:
  G-5555 shows high selectivity for the group I PAKs and it also 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. There is a negligible activity for G-5555 against the hERG channel with IC50 more than 10 μM in a patch-clamp assay. G-5555 potently inhibits PAK2 (Ki: 11 nM). G-5555 has obviously greater growth inhibitory activity in cell lines that are PAK-amplified compared to non-amplified lines, in an array of 23 breast cancer cell lines.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

inhibit, PAK, PAK2, PAK1, Inhibitor, G 5555, G5555, G-5555, p21 activated kinases

Compound Identifiers

PubChem CID

91664373