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Details

Stereochemistry ACHIRAL
Molecular Formula C18H22N4O2
Molecular Weight 326.3936
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PEFICITINIB

SMILES

c1cnc2-c1c(c(c[nH]2)C(=N)O)N[C@@]3([H])[C@@]4([H])CC5([H])C[C@]3([H])C[C@@](C5)(C4)O

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+

HIDE SMILES / InChI

Molecular Formula C18H22N4O2
Molecular Weight 326.3936
Charge 0
Count
Stereochemistry MIXED
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: The description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT02308163 | https://clinicaltrials.gov/ct2/show/NCT02305849 | https://www.drugbank.ca/drugs/DB11708 | https://www.ncbi.nlm.nih.gov/pubmed/28118538 | https://www.ncbi.nlm.nih.gov/pubmed/26351728 | https://www.ncbi.nlm.nih.gov/pubmed/28117214

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
3.9 nM [IC50]
5.0 nM [IC50]
0.71 nM [IC50]
4.8 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
In vitro/in vivo investigations to examine the gender differences in the pharmacokinetics of novel oral Janus kinase (JAK) inhibitor ASP015K and sulfate metabolite M2 in rats.
2015
A phase 2a randomized, double-blind, placebo-controlled, sequential dose-escalation study to evaluate the efficacy and safety of ASP015K, a novel Janus kinase inhibitor, in patients with moderate-to-severe psoriasis.
2015 Sep
Patents

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.
Substance Class Chemical
Created
by admin
on Sat Jun 26 14:02:06 UTC 2021
Edited
by admin
on Sat Jun 26 14:02:06 UTC 2021
Record UNII
HPH1166CKX
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PEFICITINIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
PEFICITINIB [INN]
Common Name English
JNJ-54781532
Code English
PEFICITINIB [WHO-DD]
Common Name English
PEFICITINIB [USAN]
Common Name English
4-((TRANS-5-HYDROXYADAMANTAN-2-YL)AMINO)-1H-PYRROLO(2,3-B)PYRIDINE-5-CARBOXAMIDE
Systematic Name English
ASP015K
Code English
ASP-015K
Code English
PEFICITINIB HYDROBROMIDE [JAN]
Common Name English
4-((ANTI-5-HYDROXYADAMANTAN-2-YL)AMINO)-1H-PYRROLO(2,3-B)PYRIDINE-5-CARBOXAMIDE
Systematic Name English
Code System Code Type Description
CAS
944118-01-8
Created by admin on Sat Jun 26 14:02:07 UTC 2021 , Edited by admin on Sat Jun 26 14:02:07 UTC 2021
PRIMARY
NCI_THESAURUS
C170291
Created by admin on Sat Jun 26 14:02:07 UTC 2021 , Edited by admin on Sat Jun 26 14:02:07 UTC 2021
PRIMARY
FDA UNII
HPH1166CKX
Created by admin on Sat Jun 26 14:02:07 UTC 2021 , Edited by admin on Sat Jun 26 14:02:07 UTC 2021
PRIMARY
ChEMBL
CHEMBL3137308
Created by admin on Sat Jun 26 14:02:07 UTC 2021 , Edited by admin on Sat Jun 26 14:02:07 UTC 2021
PRIMARY
INN
9910
Created by admin on Sat Jun 26 14:02:07 UTC 2021 , Edited by admin on Sat Jun 26 14:02:07 UTC 2021
PRIMARY
EVMPD
SUB184949
Created by admin on Sat Jun 26 14:02:07 UTC 2021 , Edited by admin on Sat Jun 26 14:02:07 UTC 2021
PRIMARY
DRUG BANK
DB11708
Created by admin on Sat Jun 26 14:02:07 UTC 2021 , Edited by admin on Sat Jun 26 14:02:07 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
IC50
TARGET -> INHIBITOR
IC50
TARGET -> INHIBITOR
IC50
Related Record Type Details
ACTIVE MOIETY