| Identification | Back Directory | [Name]
Peficitinib hydrobromide (JAN/USAN) | [CAS]
1353219-05-2 | [Synonyms]
Peficitinib hydrobromide
Peficitinib hydrobromide (JAN/USAN)
4-(5-Hydroxytricyclo3.3.1.13,7dec-2-yl)amino-1H-pyrrolo2,3-bpyridine-5-carboxamide hydrobromide (1:1) stereoisomer | [Molecular Formula]
C18H22N4O2. HBr | [MDL Number]
MFCD30747936 | [MOL File]
1353219-05-2.mol | [Molecular Weight]
407.31 |
| Chemical Properties | Back Directory | [InChI]
InChI=1S/C18H22N4O2.BrH/c19-16(23)13-8-21-17-12(1-2-20-17)15(13)22-14-10-3-9-4-11(14)7-18(24,5-9)6-10;/h1-2,8-11,14,24H,3-7H2,(H2,19,23)(H2,20,21,22);1H | [InChIKey]
ZUVPMAPXNYGJQC-UHFFFAOYSA-N | [SMILES]
N(C1C(=CN=C2NC=CC=12)C(=O)N)C1C2CC3CC(O)(C2)CC1C3.Br |
| Hazard Information | Back Directory | [Uses]
Peficitinib (ASP015K) hydrobromide is an orally active JAK inhibitor, with IC50s of 3.9, 5.0, 0.7 and 4.8 nM for JAK1, JAK2, JAK3 and Tyk2, respectively[1]. | [Mechanism of action]
Peficitinib hydrobromide potently inhibits the JAK-STAT pathway and blocks the signaling of pro-inflammatory cytokines such as IL-6 and IFN-γ. It has the strongest inhibitory activity against JAK3 (IC₅₀ = 0.7 nM), while also taking into account other subtypes (JAK1/2/Tyk2 IC₅₀ 3.9–5.0 nM). | [Synthesis]
Synthesis of Peficitinib hydrobromide  | [in vivo]
Peficitinib hydrobromide (1-30 mg/kg; p.o.; once daily for 24 days) shows dose-dependent efficacy both in prophylactic and therapeutic dosing regimens in an adjuvant-induced arthritis rat model[1]. | Animal Model: | Seven-weeks-old female Lewis rats, adjuvant-induced arthritis (AIA) model[1] | | Dosage: | 1, 3, 10, and 30 mg/kg | | Administration: | Oral administration, once daily for 24 days | | Result: | Significantly inhibited the increase in paw volume at doses of 1 mg/kg or greater with an ED50 value of 2.7 mg/kg (95% confidence interval: 1.5–4.2 mg/kg). Significantly reduced the bone destruction score at 10 mg/kg or greater and almost fully ameliorated both paw swelling and bone destruction scores at 30 mg/kg.
|
| [IC 50]
JAK3: 0.7 nM (IC50); JAK1: 3.9 nM (IC50); Tyk2: 4.8 nM (IC50); JAK2: 5 nM (IC50) | [References]
[1] Ito M, et al. A novel JAK inhibitor, peficitinib, demonstrates potent efficacy in a rat adjuvant-induced arthritis model. J Pharmacol Sci. 2017 Jan;133(1):25-33. DOI:10.1016/j.jphs.2016.12.001 |
|
|