AMG-25 (AMG25) is a novel, oral, potent and selective inhibitor of c-Kit with anticancer activity and desirable pharmacokinetic properties. It inhibits c-Kit with IC50s of 22 nM and 16 nM in kinase assay and cell assay, respectively.

Physicochemical Properties

Molecular Formula	C23H17N5O2EXACTMASS
Molecular Weight	395.4134
Exact Mass	395.138
CAS #	1003311-62-3
PubChem CID	24879368
Appearance	Light yellow to light brown solid powder
Density	1.4±0.1 g/cm3
Boiling Point	720.7±70.0 °C at 760 mmHg
Flash Point	389.7±35.7 °C
Vapour Pressure	0.0±2.3 mmHg at 25°C
Index of Refraction	1.709
LogP	2.78
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	3
Heavy Atom Count	30
Complexity	714
Defined Atom Stereocenter Count	0
InChi Key	IGFSMGCBFTXTJK-UHFFFAOYSA-N
InChi Code	InChI=1S/C23H17N5O2/c1-14-8-10-28(18-5-2-15(3-6-18)21-25-9-11-30-21)22(29)20(14)16-4-7-19-17(12-16)13-26-23(24)27-19/h2-13H,1H3,(H2,24,26,27)
Chemical Name	3-(2-aminoquinazolin-6-yl)-4-methyl-1-[4-(1,3-oxazol-2-yl)phenyl]pyridin-2-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
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	Compound 25, also known as c-Kit-IN-5, has selectivity against KDR, p38, Lck, and Src that is more than 200 times higher (IC50=>5.0, 40, 7.8, and >5.0 μM, respectively)[1].
ln Vivo	c-Kit-IN-5 (compound 25) (1 mg/kg; iv) demonstrates CL (0.46 L/h/kg) and Vdss (1.59 L/kg) in rats[1]. c-Kit-IN-5 (10 mg/kg; po) demonstrates AUC0-t(9860 ng·h/mL) Cmax(1230 ng/mL), T1/2 (2.6 h), and F (39%) in rats[1].
References	[1]. Discovery of aryl aminoquinazoline pyridones as potent, selective, and orally efficacious inhibitors of receptor tyrosine kinase c-Kit. J Med Chem. 2008 Jun 12;51(11):3065-8.

Solubility Data

Solubility (In Vitro)

DMSO : ~25 mg/mL (~63.23 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 1.67 mg/mL (4.22 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 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: 1.67 mg/mL (4.22 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5290 mL	12.6451 mL	25.2902 mL
	5 mM	0.5058 mL	2.5290 mL	5.0580 mL
	10 mM	0.2529 mL	1.2645 mL	2.5290 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.