| Stereochemistry | ACHIRAL |
| Molecular Formula | C18H22N4O2 |
| Molecular Weight | 326.3929 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 4 / 5 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
NC(=O)C1=C(N[C@H]2[C@H]3CC4C[C@@H]2C[C@@](O)(C4)C3)C5=C(NC=C5)N=C1
InChI
InChIKey=DREIJXJRTLTGJC-RRBRBRQDSA-N
InChI=1S/C18H22N4O2/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)/t9?,10-,11+,14-,18+
| Molecular Formula | C18H22N4O2 |
| Molecular Weight | 326.3929 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | MIXED |
| Additional Stereochemistry | No |
| Defined Stereocenters | 3 / 5 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
Peficitinib (formerly known as ASP015K) is a pyrrolo[2,3-b]pyridine derivative orally administered once-daily JAK inhibitor in development for the treatment of Rheumatoid Arthritis. In preclinical studied Peficitinib inhibited JAK1 and JAK3 with IC50 of 3.9 and 0.7 nM, respectively. Peficitinib also inhibited IL-2-dependent T cell proliferation in vitro and STAT5 phosphorylation in vitro and ex vivo. Furthermore, Peficitinib dose-dependently suppressed bone destruction and paw swelling in an adjuvant-induced arthritis model in rats via prophylactic or therapeutic oral dosing regimens.In clinical trials, Peficitinib treatment prescribed at 50, 100 and 150 mg amounts each showed statistically significantly higher ACR20 response rates compared to the placebo and response rates increased up to the 150 mg dosage. Adverse events included neutropenia, headache, and abdominal pain. The treatment-emergent adverse events occurring more frequently in the Peficitinib group compared with the placebo group included diarrhea, nasopharyngitis, and increased serum creatine phosphokinase activity. No cases of serious infections were reported. Herpes zoster occurred in four patients (two each in the peficitinib 25 and 100 mg cohorts). The authors concluded that treatment with peficitinib as monotherapy for 12 weeks in Japanese patients with moderate to severe RA is efficacious and showed an acceptable safety profile.
Originator
Approval Year
Sourcing
PubMed
Patents
Sample Use Guides
25 mg, 50 mg, 100 mg, or 150 mg once daily for 12 weeks.
Route of Administration:
Oral
Splenocytes from male Lewis rats were suspended in RPMI1640 (Sigma, St. Louis, MO, USA) supplemented with 10% fetal bovine serum and 50 mkM 2-mercaptoethanol at a density of 1.5 x 10^6 cells/mL. Rat splenocytes were cultured with Concanavalin A (Sigma) for 24 h at 37 C to induce IL-2 receptor expression. Splenocytes were then incubated with IL-2 (BD Biosciences, San Diego, CA, USA) and peficitinib or tofacitinib at designated concentrations in 96-well tissue culture plates. After 3-day incubation, alamarBlue® (Life Technologies, Carlsbad, CA, USA) was added to each of the test wells, followed by 4-6 h incubation. Fluorescence intensity was measured at an excitation wavelength of 545 nm and an emission wavelength of 590 nm.
