CCR4-351 hydrochloride

• CAT Number: I045464
• CAS Number: 2174938-71-5
• Molecular Formula: C24H28Cl3N7O
• Purity: ≥95%

CCR4-351 hydrochloride is an orally active, potent and selective CCR4 antagonist. CCR4-351 hydrochloride, featuring a novel piperidinyl-azetidine motif, has IC50s of 22 nM and 50 nM in the calcium flux and CTX assay. CCR4-351 hydrochloride has antitumor activity[1].
CCR4-351 (compound 38) hydrochloride shows no activity in a CYP450 induction assay[1].
CCR4-351 hydrochloride inhibits the migration of mouse iTreg cells with an IC50 of 39 nM, while the IC50 in human iTreg cells is 33 nM[1].
CCR4-351 (compound 38; 50 mg/kg; PO; daily; for 40 days) hydrochloride significantly reduces the tumor growth[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), a T1/2 of 6.9 h, and good bioavailability (%F = 29) of oral dosing in mouse[1].
CCR4-351 hydrochloride has low clearance (CL=7.3 mL/min/kg), a half-life of 12.7 hr, and is 44% bioavailable in dog. CCR4-351 hydrochloride has low clearance (CL=3.7 mL/min/kg), a long terminal half-life (10.7 hr), and good bioavailability (%F = 41) in cynomolgus monkey[1].

Reference

[1]. Omar Robles, et al. 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.
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