C021 (C-021; CCR4 antagonist) is a novel and potent CCR4 antagonist with anti-inflammatory activity. It exhibits IC50 of 0.039 and 0.14 μM for inhibition of chemotaxis in mouse and human, respectively.

Physicochemical Properties

Molecular Formula	2[C27H41N5O2].6[HCL].3[H2O]
Molecular Weight	1208.10496
Exact Mass	467.326
CAS #	864289-85-0
Related CAS #	C-021 dihydrochloride;1784252-84-1
PubChem CID	25141190
Appearance	Off-white to light yellow solid powder
LogP	5.312
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	6
Heavy Atom Count	34
Complexity	602
Defined Atom Stereocenter Count	0
InChi Key	WYVBISCFCHREDA-UHFFFAOYSA-N
InChi Code	InChI=1S/C27H41N5O2/c1-33-24-18-22-23(19-25(24)34-2)29-27(30-26(22)28-20-10-6-3-4-7-11-20)32-16-12-21(13-17-32)31-14-8-5-9-15-31/h18-21H,3-17H2,1-2H3,(H,28,29,30)
Chemical Name	N-cycloheptyl-6,7-dimethoxy-2-(4-piperidin-1-ylpiperidin-1-yl)quinazolin-4-amine
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	C-021 (compound 1b) was evaluated for its in vitro oxidative hindrance stability by determining its apparent clearance values (CLint) by drug consumption rate measurements in human liver microsomes (HML). The CLint value of C-021 is 17,377 mL/hour/kg [1].
ln Vivo	The efficacy of C-021 (compound 1b) is preliminary as a subcutaneous medication in an oxazolone-induced contact hypersensitivity assay in mice, an established model of acute skin toxicity. However, when dose C-C-021 (1 mg/kg; i.p.; daily; for 3 days) was duplicated in acute hepatic mice, small cell apoptosis was seen [2]. At 021, virtually little inhibition was detected [1].
Animal Protocol	Animal/Disease Models: Male C57Bl/6 mice with acute liver failure (20-25 g) [2] Doses: 1 mg/kg Route of Administration: intraperitoneal (ip) injection; daily; continued for 3 days Experimental Results: Microglia Hyperplasia was Dramatically diminished, and the ratio of pERK1/2 to tERK1/2 was Dramatically diminished.
References	[1]. Potent and orally bioavailable CCR4 antagonists: Synthesis and structure-activity relationship study of 2-aminoquinazolines. Bioorg Med Chem. 2009 Jan 1;17(1):64-73. [2]. Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline. J Neuroinflammation. 2014 Jul 10;11:121.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~106.92 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 0.71 mg/mL (1.52 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 7.1 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: ≥ 0.71 mg/mL (1.52 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 7.1 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: ≥ 0.71 mg/mL (1.52 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 7.1 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	0.8277 mL	4.1387 mL	8.2774 mL
	5 mM	0.1655 mL	0.8277 mL	1.6555 mL
	10 mM	0.0828 mL	0.4139 mL	0.8277 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.