| Identification | Back Directory | [Name]
3-Piperidinecarboxamide, 1-(cyclopropylmethyl)-4-[[[5-(2,4-difluorophenyl)-3-isoxazolyl]carbonyl]amino]-N-[1-(2-pyrimidinyl)cyclopropyl]-, (3S,4S)- | [CAS]
2178049-58-4 | [Synonyms]
ACT-1004-1239
3-Piperidinecarboxamide, 1-(cyclopropylmethyl)-4-[[[5-(2,4-difluorophenyl)-3-isoxazolyl]carbonyl]amino]-N-[1-(2-pyrimidinyl)cyclopropyl]-, (3S,4S)- | [Molecular Formula]
C27H28F2N6O3 | [MOL File]
2178049-58-4.mol | [Molecular Weight]
522.55 |
| Chemical Properties | Back Directory | [Boiling point ]
751.3±60.0 °C(Predicted) | [density ]
1.42±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
6.28±0.40(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
ACT-1004-1239 is a potent, selective, orally active CXCR7 antagonist with an IC50 value of 3.2 nM[1][2]. | [in vivo]
ACT-1004-1239 (100 mg/kg, p.o.) increase of plasma CXCL12 concentration in naive male DBA/1 mice[1].
ACT-1004-1239 (100 mg/kg, p.o., twice daily) reduces disease severity in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) model[2].
ACT-1004-1239 (100 mg/kg, p.o., twice daily) increases myelination in the Cuprizone (HY-W115718)-induced demyelination model mice[2].
ACT-1004-1239 (10 mg/kg, p.o., rats) shows a Cmax of 600 ng/h/mL, Tmax of 0.5 h, F (%) of 35%[1].
ACT-1004-1239 (1 mg/kg, i.v., rats) shows a Vss of 3.6 L/kg, Cl of 70 mL/min/kg, T1/2 of 1.3 h[1].
| Animal Model: | Myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) model[2] | | Dosage: | 10-100 mg/kg | | Administration: | p.o., twice daily | | Result: | Reduced clinical disease scores, and increases survival rate.
Increases plasma CXCL12 concentration.
Reduces the infiltration of neutrophils, monocytes, monocytes-derived cells (MdCs), plasmacytoid dendritic cells (pDCs), DCs, natural killer (NK) cells, NK T cells, B cells, and T cells.
Reduces the number of CXCR4-expressing leukocytes. |
| [IC 50]
CXCR7 | [References]
[1] Richard-Bildstein S, et al. Discovery of the Potent, Selective, Orally Available CXCR7 Antagonist ACT-1004-1239. J Med Chem. 2020 Dec 24;63(24):15864-15882. DOI:10.1021/acs.jmedchem.0c01588
[2] Pouzol L, et al. ACT-1004-1239, a first-in-class CXCR7 antagonist with both immunomodulatory and promyelinating effects for the treatment of inflammatory demyelinating diseases. FASEB J. 2021 Mar;35(3):e21431. DOI:10.1096/fj.202002465R |
|
|