CCR4-351

• CAT Number: I045758
• CAS Number: 2174938-70-4
• Molecular Formula: C24H27Cl2N7O
• Molecular Weight: 500.42
• Purity: ≥95%
• Synonyms: 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[3-[(3R)-1-(2-hydroxyethyl)piperidin-3-yl]azetidin-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile
• InChI: InChI=1S/C24H27Cl2N7O/c1-15(19-5-4-18(25)9-20(19)26)33-24-23(21(10-27)30-33)28-11-22(29-24)32-13-17(14-32)16-3-2-6-31(12-16)7-8-34/h4-5,9,11,15-17,34H,2-3,6-8,12-14H2,1H3/t15-,16+/m1/s1
• InChIKey: PNCGVFJZWKHMCL-CVEARBPZSA-N
• SMILES: CC(C1=C(C=C(C=C1)Cl)Cl)N2C3=NC(=CN=C3C(=N2)C#N)N4CC(C4)C5CCCN(C5)CCO

CCR4-351 is an orally active, potent and selective CCR4 antagonist. CCR4-351, featuring a novel piperidinyl-azetidine motif, has IC50s of 22 nM and 50 nM in the calcium flux and CTX assay. CCR4-351 has antitumor activity[1].
CCR4-351 (compound 38) shows no activity in a CYP450 induction assay[1].
CCR4-351 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) significantly reduces the tumor growth[1].
CCR4-351 (0.5 mg/kg; IV) 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 has low clearance (CL=7.3 mL/min/kg), a half-life of 12.7 hr, and is 44% bioavailable in dog. CCR4-351 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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