ACT-660602

• CAT Number: I042867
• CAS Number: 1646267-59-5
• Molecular Formula: C20H20F6N8OS
• Molecular Weight: 534.48
• Purity: ≥95%
• Synonyms: 2-(3,5-dimethyl-1,2,4-triazol-1-yl)-1-[(2R)-2-methyl-4-[2-(trifluoromethyl)-4-[2-(trifluoromethyl)pyrimidin-5-yl]-1,3-thiazol-5-yl]piperazin-1-yl]ethanone
• InChI: InChI=1S/C20H20F6N8OS/c1-10-8-32(4-5-33(10)14(35)9-34-12(3)29-11(2)31-34)16-15(30-18(36-16)20(24,25)26)13-6-27-17(28-7-13)19(21,22)23/h6-7,10H,4-5,8-9H2,1-3H3/t10-/m1/s1
• InChIKey: JENUMEXEVAAAJX-SNVBAGLBSA-N
• SMILES: CC1CN(CCN1C(=O)CN2C(=NC(=N2)C)C)C3=C(N=C(S3)C(F)(F)F)C4=CN=C(N=C4)C(F)(F)F

ACT-660602 is an orally active antagonist of chemokine receptor (CXCR3) with an IC50 value of 204 nM. ACT-660602 inhibits T-cell migration and shows efficacy in acute lung ingury model. ACT-660602 can be used for autoimmune diseases research[1][2].
ACT-660602 shows selectivity to CXCR3 over hERG, with IC50s of 18 μM (hERG)[1].
ACT-660602 (112 nM; 6 h) inhibits cell migration and improves the metabolic stability[1].
ACT-660602 (5, 20, 100 or 500 nM) displays an non-competitive binding mode to CXCL10 and CXCL11 in different concentration, with more stable IC50s[1].
ACT-660602 (1 μM; 6 h) intrinsic metabolic clearance (CLint) in human, rat, mouse liver microsomes (HLM, RLM, MLM)[1].
ACT-660602 (30 mg/kg; p.o.; once daily) displays anti-inflammatory activity and exerts efficacy in the mouse model of acute lung ingury[1].
Range for Pharmacokinetics of ACT-660602[1]

Animal
Route
Dose (range) (mg/kg)
Cmax (range) (ng/mL)
Tmax (range) (h)
AUC (range) (ng•h/mL)
F (%)
CL (range) (mL/min/kg)
Vss (range) (L/kg)
T1/2 (range) (h)

Dog
p.o.
2
1380
1
20000
8
1.3
1.7
14.5

i.v.
0.5
1300-1450
0.5-2.0
10400-32000
/
0.6-3.0
1.6-1.7
6.3-

Rat
p.o.
2
1520
0.5
14000
80
1.9
1.1
7.1

i.v.
0.5
1250-1860
0.5-1.0
11600-15641
/
1.9-1.9
0.9-1.3
5.7-8.8

Reference

[1]. Meyer EA, et al. Discovery and In Vivo Evaluation of ACT-660602: A Potent and Selective Antagonist of the Chemokine Receptor CXCR3 for Autoimmune Diseases. J Med Chem. 2022 Aug 10.
 [Content Brief]

[2]. Caroff Eva, et al. Preparation of piperazinyltriazolylethanone derivatives for use as CXCR3 receptor modulators: World Intellectual Property Organization, WO2015011099. 2015-01-29.