CE-245677 is a potent, reversible inhibitor of Tie2 and TrkA/B with IC50s of 4.7 and 1 nM respectively in cell systems.

Physicochemical Properties

Molecular Formula	C24H22CL2N6O3
Molecular Weight	513.3759
Exact Mass	512.113
CAS #	717899-97-3
Related CAS #	941588-94-9 (mesylate);717899-97-3;941588-98-3;941588-96-1 (besylate);
PubChem CID	16048643
Appearance	White to off-white solid powder
LogP	4.1
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	6
Heavy Atom Count	35
Complexity	761
Defined Atom Stereocenter Count	0
SMILES	ClC1C([H])=C(C([H])=C([H])C=1N([H])C(N([H])C1=C(C([H])=C([H])C(=C1[H])C(C1=C([H])N(C2C1=C(N([H])[H])N=C([H])N=2)C([H])(C([H])([H])[H])C([H])([H])[H])=O)OC([H])([H])[H])=O)Cl
InChi Key	VFCRSIORGUNNGT-UHFFFAOYSA-N
InChi Code	InChI=1S/C24H22Cl2N6O3/c1-12(2)32-10-15(20-22(27)28-11-29-23(20)32)21(33)13-4-7-19(35-3)18(8-13)31-24(34)30-17-6-5-14(25)9-16(17)26/h4-12H,1-3H3,(H2,27,28,29)(H2,30,31,34)
Chemical Name	1-[5-(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidine-5-carbonyl)-2-methoxyphenyl]-3-(2,4-dichlorophenyl)urea
Synonyms	CE245677; CE 245677; CE-245677
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	CE-245677 exhibits >100-fold action against numerous additional angiogenic receptor tyrosine kinases (e.g., KDR, PDGFR, FGFR) selectivity. It is a strong and reversible inhibitor of Tie2 and TrkA/B kinases, with cellular IC50s of 4.7 and 1 nM, respectively[1].
ln Vivo	CE-245677 demonstrated good oral absorption (F=80%) in a rat PK investigation conducted in vivo [1].
References	[1]. Identification of selective, orally active Tie2 kinase inhibitors and discovery of CE-245,677 and PF-371,989. Cancer Research. AACR Annual Meeting-Apr 14-18, 2007.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~243.48 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.05 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 (4.05 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 20.8 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	1.9479 mL	9.7394 mL	19.4787 mL
	5 mM	0.3896 mL	1.9479 mL	3.8957 mL
	10 mM	0.1948 mL	0.9739 mL	1.9479 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.