Peficitinib hydrobromide CAS 1353219-05-2

Introduction：Basic information about Peficitinib hydrobromide CAS 1353219-05-2, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Peficitinib hydrobromide Basic information

• Product Name: Peficitinib hydrobromide
• Synonyms: Peficitinib hydrobromide (JAN/USAN);Peficitinib hydrobromide;4-(5-Hydroxytricyclo3.3.1.13,7dec-2-yl)amino-1H-pyrrolo2,3-bpyridine-5-carboxamide hydrobromide (1:1) stereoisomer;Peficitinib Hydrobromid;anti-4-((5-Hydroxyadamantan-2-yl)amino)-1H-pyrrolo[2,3-b]pyridine-5-carboxamide hydrobromide;RMA-849
• CAS: 1353219-05-2
• MF: C18H22N4O2. HBr
• MW: 407.31
• Mol File: 1353219-05-2.mol

Peficitinib hydrobromide Chemical Properties

• 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

Peficitinib hydrobromide Usage And Synthesis

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