G-5555 is a potent PAK1 inhibitor (antagonist) with Kis of 3.7 nM and 11 nM for PAK1 and PAK2 respectively.

Physicochemical Properties

Molecular Formula	C25H26CL2N6O3
Molecular Weight	529.4183
Exact Mass	492.167
CAS #	1648863-90-4
Related CAS #	G-5555 hydrochloride
PubChem CID	91664373
Appearance	White to light yellow solid powder
Density	1.4±0.1 g/cm3
Boiling Point	684.6±65.0 °C at 760 mmHg
Flash Point	367.8±34.3 °C
Vapour Pressure	0.0±2.1 mmHg at 25°C
Index of Refraction	1.652
LogP	1.98
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	5
Heavy Atom Count	35
Complexity	778
Defined Atom Stereocenter Count	0
InChi Key	ZBCMHWUFWQFPLV-UHFFFAOYSA-N
InChi Code	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)
Chemical Name	8-[(5-amino-1,3-dioxan-2-yl)methyl]-6-[2-chloro-4-(6-methylpyridin-2-yl)phenyl]-2-(methylamino)pyrido[2,3-d]pyrimidin-7-one
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	G-5555 has a Ki of 3.7 nM, making it a strong PAK1 conjugate. Of the 235 interactions evaluated, G-5555 shown good interactions, modifying but inhibiting 8 of them by more than 70%: PAK2, PAK3, KHS1, Lck, MST3, MST4, SIK2, and YSK1. G-5555 has an IC50 of 9, 11, 10, 20, 34, 43, and 52 nM against SIK2, PAK2, KHS1, MST4, YSK1, MST3, and Lck, in that order. G-5555 generally shows good selectivity for group I PAKs. G-5555 exhibits very little action on hERG channels in patch-clamp studies, with an IC50 greater than 10 μM [1]. G-5555 inhibits PAK2 potently, having a Ki of 11 nM. G-5555 had much more growth inhibitory action in the PAK cell line than in non-amplified cell lines in a panel of 23 tumor cell lines [2].
ln Vivo	G-5555 has a deadly half-life and poor blood clearance. High oral bioavailability (F=80%) and good oral exposure (AUC=30 μM h) were attained [1]. G-5555 inhibited phosphorylation of the PAK1/2 downstream substrate mitogen-activated protein kinase 1 (MEK1) S298 in a simulator H292 non-small cell lung cancer (NSCLC) xenograft study. When given at a final dose of 25 mg hour/kg bid, this model and the PAK1 breast cancer xenograft model MDAMB-175 showed 60% tumor growth inhibition [2].
References	[1]. 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]. 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.

Solubility Data

Solubility (In Vitro)

DMSO : ~25 mg/mL (~50.71 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.07 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 (5.07 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.07 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly.  (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.