CCR4-351 hydrochloride is a sidewall potent and selective CCR4-clamping antioxidant. CCR4-351 hydrochloride has a novel ring third base-azetidine motif and has IC50 of 22nM and 50nM in calcium flux and CTX assays. CCR4-351 hydrochloride has anti-tumor activity.

Physicochemical Properties

Molecular Weight	536.88
CAS #	2174938-71-5
Related CAS #	CCR4-351;2174938-70-4
Appearance	White to off-white solid powder
SMILES	[C@@H](C1C=CC(Cl)=CC=1Cl)(N1N=C(C#N)C2=NC=C(N3CC([C@H]4CCCN(CCO)C4)C3)N=C12)C.Cl
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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 CYP450 induction experiments, CCR4-351 (compound 38) hydrochloride has no activity [1]. The migration of mouse iTreg cells is inhibited by CCR4-351 hydrochloride at an IC50 of 39 nM, whereas the IC50 of human iTreg cells is 33 nM [1].
ln Vivo	CCR4-351 (Compound 38; 50 mg/kg; oral; daily; for 40 days) hydrochloride effectively decreases tumor development [1]. CCR4-351 (0.5 mg/kg; IV) hydrochloride has low clearance (CL=10.2 mL/min/kg), medium volume of distribution (Vss=5.2 L/kg), T1/2 of 6.9 h and high Bioavailability (%F = 29) Oral delivery to mice [1]. CCR4-351 hydrochloride has a low clearance (CL=7.3 mL/min/kg), a half-life of 12.7 hours, and a bioavailability of 44% in dogs. CCR4-351 hydrochloride has low clearance (CL=3.7 mL/min/kg), extended terminal half-life (10.7 hours), and good bioavailability (%F = 41) in cynomolgus monkeys [1].
Animal Protocol	Animal/Disease Models: 6 to 8 weeks old female C57BL/6 mice with Pan02-OVA tumors [1] Doses: 50 mg/kg Route of Administration: Oral; daily; continued for 40 days Experimental Results: Significant reduction in tumor growth . Animal/Disease Models: Rat and Mouse[1] Doses: 0.5 mg/kg IV; 2 mg/kg PO Route of Administration: IV or PO Experimental Results: Rats had moderate clearance after oral administration (CL=47.6 mL/min /kg) and the bioavailability is 49%. Oral administration to mice demonstrated low clearance (CL=10.2 mL/min/kg), medium volume of distribution (Vss=5.2 L/kg), T1/2 of 6.9 hrs (hrs (hours)), and good bioavailability (%F = 29) .
References	[1]. Novel Piperidinyl-Azetidines as Potent and Selective CCR4 Antagonists Elicit Antitumor Response as Single Agent and in Combination with Checkpoint Inhibitors. J Med Chem. 2020 Jul 15.

Solubility Data

Solubility (In Vitro)

DMSO : ~170 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 4.25 mg/mL (Infinity 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 42.5 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: ≥ 4.25 mg/mL (Infinity 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 42.5 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	1.8626 mL	9.3131 mL	18.6261 mL
	5 mM	0.3725 mL	1.8626 mL	3.7252 mL
	10 mM	0.1863 mL	0.9313 mL	1.8626 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.