CCT137690 is a novel, potent, highly selective and orally bioavailable inhibitor of Aurora kinase A/B/C with potential antitumor activity. It inhibits Aurora A/B/C with IC50s of 15 nM, 25 nM and 19 nM respectively and shows no/little effect on hERG potassium ion-channel. CCT137690 shows potent in vitro antiproliferative activity and high in vivo antitumor efficacy.

Physicochemical Properties

Molecular Formula	C26H31BRN8O
Molecular Weight	551.48
Exact Mass	550.18
CAS #	1095382-05-0
Related CAS #	1095382-05-0
PubChem CID	25154041
Appearance	White to light yellow solid powder
Density	1.4±0.1 g/cm3
Boiling Point	722.9±70.0 °C at 760 mmHg
Flash Point	391.0±35.7 °C
Vapour Pressure	0.0±2.3 mmHg at 25°C
Index of Refraction	1.664
LogP	3.07
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	5
Heavy Atom Count	36
Complexity	710
Defined Atom Stereocenter Count	0
InChi Key	GFLQCBTXTRCREJ-UHFFFAOYSA-N
InChi Code	InChI=1S/C26H31BrN8O/c1-18-15-20(31-36-18)17-33-9-13-35(14-10-33)24-22(27)16-28-26-23(24)29-25(30-26)19-3-5-21(6-4-19)34-11-7-32(2)8-12-34/h3-6,15-16H,7-14,17H2,1-2H3,(H,28,29,30)
Chemical Name	6-Bromo-7-[4-[(5-methyl-3-isoxazolyl)methyl]-1-piperazinyl]-2-[4-(4-methyl-1-piperazinyl)phenyl]-3H-imidazo[4,5-b]pyridine
Synonyms	CCT-137690; CCT 137690; CCT137690
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	In a variety of human tumor cell lines, such as the SW620 colon carcinoma (GI50=0.30 μM) and the A2780 ovarian cancer cell line (GI50=0.14 μM), CCT 137690 exhibits antiproliferative activity. In vitro phosphorylation of histone H3 is inhibited by CCT 137690. The hERG ion-channel is moderately inhibited by CCT 137690 (IC50=3.0 μM)[1]. HeLa and HCT116 cells are effectively inhibited by CCT137690-mediated phosphorylation of histone H3 and TACC3, which are substrates for Aurora B and Aurora A, respectively. Multipolar spindle formation, chromosome misalignment, polyploidy, and apoptosis are all brought on by the inhibitor's continuous exposure to tumor cells[2].
ln Vivo	With no discernible toxicity, CCT 137690 reduces the growth of the SW620 xenografts[1]. In a transgenic mouse model of neuroblastoma (TH-MYCN) that overexpresses MYCN protein and is susceptible to spontaneous neuroblastoma development, CCT 137690 effectively reduces tumor growth[2].
Animal Protocol	Dissolved in DMSO-Tween-saline; 75 mg/kg; Oral gavage. Female CrTac:NCr-Fox1(nu) athymic mice bearing established SW620 human colorectal tumors
References	[1]. Imidazo[4,5-b]pyridine derivatives as inhibitors of Aurora kinases: lead optimization studies toward the identification of an orally bioavailable preclinical development candidate. J Med Chem. 2010 Jul 22;53(14):5213-28. [2]. The aurora kinase inhibitor CCT137690 downregulates MYCN and sensitizes MYCN-amplified neuroblastoma in vivo. Mol Cancer Ther. 2011 Nov;10(11):2115-23.

Solubility Data

Solubility (In Vitro)

DMSO: 4 mg/mL (7.2 mM) Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.67 mg/mL (3.03 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 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 (3.03 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 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. Solubility in Formulation 3: ≥ 1.67 mg/mL (3.03 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 16.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 1% DMSO+30% polyethylene glycol+1% Tween 80:~30mg/mL  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8133 mL	9.0665 mL	18.1330 mL
	5 mM	0.3627 mL	1.8133 mL	3.6266 mL
	10 mM	0.1813 mL	0.9067 mL	1.8133 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.