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.

Product information

CAS Number: 1648863-90-4

Molecular Weight: 492.96

Formula: C25H25ClN6O3

Chemical Name: 6-[2-chloro-4-(6-methylpyridin-2-yl)phenyl]-2-(methylamino)-8-{[(2r,5r)-5-amino-1,3-dioxan-2-yl]methyl}-7H,8H-pyrido[2,3-d]pyrimidin-7-one

Smiles: CC1=CC=CC(=N1)C1=CC=C(C(Cl)=C1)C1=CC2=CN=C(NC)N=C2N(C[C@@H]2OC[C@@H](N)CO2)C1=O

InChiKey: ZBCMHWUFWQFPLV-VVOJOOEHSA-N

InChi: InChI=1S/C25H25ClN6O3/c1-14-4-3-5-21(30-14)15-6-7-18(20(26)9-15)19-8-16-10-29-25(28-2)31-23(16)32(24(19)33)11-22-34-12-17(27)13-35-22/h3-10,17,22H,11-13,27H2,1-2H3,(H,28,29,31)/t17-,22-

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : ≥ 27 mg/mL (54.77 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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. 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.

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. 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.

Products are for research use only. Not for human use.