AZ12672857 is an orally bioactive inhibitor of EphB4 (IC50=1.3 nM) and Src kinase. AZ12672857 suppresses the proliferation/growth of c-Src-transfected 3T3 cells (IC50=2 nM) and inhibits EphB4 autophosphorylation in transfected CHO-K1 cells (IC50=9 nM).

Physicochemical Properties

Molecular Formula	C26H30N8O2
Molecular Weight	486.568804264069
Exact Mass	486.249
CAS #	945396-55-4
PubChem CID	49831162
Appearance	Light brown to brown solid powder
LogP	3.2
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	6
Heavy Atom Count	36
Complexity	665
Defined Atom Stereocenter Count	0
SMILES	O1CCN(CC1)C1C=C(C=C(C=1)N1CCOCC1)NC1N=CC=C(N=1)N(C)C1=CC=CC2=C1C=NN2
InChi Key	QLFGDTPACJHLRY-UHFFFAOYSA-N
InChi Code	InChI=1S/C26H30N8O2/c1-32(24-4-2-3-23-22(24)18-28-31-23)25-5-6-27-26(30-25)29-19-15-20(33-7-11-35-12-8-33)17-21(16-19)34-9-13-36-14-10-34/h2-6,15-18H,7-14H2,1H3,(H,28,31)(H,27,29,30)
Chemical Name	2-N-(3,5-dimorpholin-4-ylphenyl)-4-N-(1H-indazol-4-yl)-4-N-methylpyrimidine-2,4-diamine
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

Targets	Src
ln Vitro	Merely little CYP P450 inhibition is demonstrated by AZ12672857 (IC50=5 μM against 2C9 and 3A4, >10 μM against 1A4, 2D6, and 2C19). AZ12672857 has an IC50 of 240 nM for p-KDR inhibition in HUVEC and 58 nM for p-PDGFR-β inhibition in MG63 cell line[1].
References	[1]. Inhibitors of the tyrosine kinase EphB4. Part 3: identification of non-benzodioxole-based kinase inhibitors. Bioorg Med Chem Lett. 2010;20(21):6242-6245.

Solubility Data

Solubility (In Vitro)

DMSO: 25 mg/mL (51.38 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.27 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 20.8 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: ≥ 2.08 mg/mL (4.27 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 20.8 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	2.0552 mL	10.2760 mL	20.5520 mL
	5 mM	0.4110 mL	2.0552 mL	4.1104 mL
	10 mM	0.2055 mL	1.0276 mL	2.0552 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.