CC-671 is a dual TTK protein kinase/CDC2-like kinase (CLK2) inhibitor (antagonist) with IC50s of 0.005 and 0.006 μM for TTK and CLK2, respectively.

Physicochemical Properties

Molecular Formula	C28H28N6O4
Molecular Weight	512.559725761414
Exact Mass	512.217
Elemental Analysis	C, 65.61; H, 5.51; N, 16.40; O, 12.49
CAS #	1618658-88-0
Related CAS #	1618658-88-0
PubChem CID	117881270
Appearance	Off-white to light green solid powder
LogP	5.2
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	7
Heavy Atom Count	38
Complexity	814
Defined Atom Stereocenter Count	0
InChi Key	CWJLAVRXVFHDSJ-UHFFFAOYSA-N
InChi Code	InChI=1S/C28H28N6O4/c1-15-31-21-10-8-16(12-23(21)37-15)19-14-30-25-24(19)27(38-18-6-4-5-7-18)34-28(33-25)32-20-11-9-17(26(35)29-2)13-22(20)36-3/h8-14,18H,4-7H2,1-3H3,(H,29,35)(H2,30,32,33,34)
Chemical Name	4-[[4-cyclopentyloxy-5-(2-methyl-1,3-benzoxazol-6-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-methoxy-N-methylbenzamide
Synonyms	CC671; CC 671; CC-671
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	CLK2 (IC50 = 0.006 μM)
ln Vitro	CC-671 (compound 23) is a dual inhibitor of TTK protein kinase and CDC2-like kinase (CLK2), with IC50 values for TTK and CLK2 of 0.005 and 0.006 μM, respectively. Only four kinases—CLK2, CAMKK2, PIP4K22, and JNK—show cellular binding of 75% or more in HCT-116 cell lysates treated with CC-671 at 3 μM for 1 hour[1].
ln Vivo	CC-671 (compound 23) exhibits a noteworthy 71% tumor growth inhibition (TGI) (vehicle-treated/vehicle) ×100%) at doses of 10 and 20 mg/kg when administered on a once-every-three-day (q3d) basis. Body weight loss (BWL) was greater in the group treated with CC-671 (20 mg/kg) than in the group treated with 10 mg/kg (17% vs. 5%)[1].
Enzyme Assay	Compound 23 (CC-671) kinase selectivity profile is evaluated. The CC-671 concentration is maintained at 3 μM throughout the screen. Kinase binding assays are used to quantify the TTK binding affinity. The ATP-competitive kinase inhibitor scaffold, which is proprietary and labeled with Alexa Fluor 647, is the basis for the kinase binding assays[1].
Animal Protocol	Subcutaneous injection of 5×106 Cal-51 cells is administered to female SCID mice. Randomized mice bearing 125 mm3 tumors are administered CC-671 (compound 23) intravenously at different intervals and doses (n=8–10/group). For the course of the investigation, tumors are measured twice a week. Tumor volumes are computed by measuring each tumor's long and short axes in millimeters with a digital caliper[1].
References	[1]. The Discovery of a Dual TTK Protein Kinase/CDC2-Like Kinase (CLK2) Inhibitor for the Treatmentof Triple Negative Breast Cancer Initiated from a Phenotypic Screen. J Med Chem. 2017 Nov 9;60(21):8989-9002.

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 60 mg/mL (~117.1 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.06 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 (4.06 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 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. Solubility in Formulation 3: 2.08 mg/mL (4.06 mM) 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	1.9510 mL	9.7550 mL	19.5099 mL
	5 mM	0.3902 mL	1.9510 mL	3.9020 mL
	10 mM	0.1951 mL	0.9755 mL	1.9510 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.