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| | 3-Piperidinecarboxamide, 1-(cyclopropylmethyl)-4-[[[5-(2,4-difluorophenyl)-3-isoxazolyl]carbonyl]amino]-N-[1-(2-pyrimidinyl)cyclopropyl]-, (3S,4S)- Basic information |
| | 3-Piperidinecarboxamide, 1-(cyclopropylmethyl)-4-[[[5-(2,4-difluorophenyl)-3-isoxazolyl]carbonyl]amino]-N-[1-(2-pyrimidinyl)cyclopropyl]-, (3S,4S)- Chemical Properties |
| Boiling point | 751.3±60.0 °C(Predicted) | | density | 1.42±0.1 g/cm3(Predicted) | | pka | 6.28±0.40(Predicted) | | form | Solid | | color | White to off-white |
| | 3-Piperidinecarboxamide, 1-(cyclopropylmethyl)-4-[[[5-(2,4-difluorophenyl)-3-isoxazolyl]carbonyl]amino]-N-[1-(2-pyrimidinyl)cyclopropyl]-, (3S,4S)- Usage And Synthesis |
| 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 |
| | 3-Piperidinecarboxamide, 1-(cyclopropylmethyl)-4-[[[5-(2,4-difluorophenyl)-3-isoxazolyl]carbonyl]amino]-N-[1-(2-pyrimidinyl)cyclopropyl]-, (3S,4S)- Preparation Products And Raw materials |
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