ChemicalBook Product Catalog API Inhibitors Peficitinib hydrobromide

Peficitinib hydrobromide

Product NamePeficitinib hydrobromide
CAS1353219-05-2
MFC18H22N4O2.BrH
MW407.31
EINECS
MOL File1353219-05-2.mol

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

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 Peficitinib hydrobromide synthesis

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