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Details

Stereochemistry ABSOLUTE
Molecular Formula C15H19N5O
Molecular Weight 285.3443
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RITLECITINIB

SMILES

C[C@H]1CC[C@H](CN1C(=O)C=C)NC2=C3C=CNC3=NC=N2

InChI

InChIKey=CBRJPFGIXUFMTM-WDEREUQCSA-N
InChI=1S/C15H19N5O/c1-3-13(21)20-8-11(5-4-10(20)2)19-15-12-6-7-16-14(12)17-9-18-15/h3,6-7,9-11H,1,4-5,8H2,2H3,(H2,16,17,18,19)/t10-,11+/m0/s1

HIDE SMILES / InChI

Molecular Formula C15H19N5O
Molecular Weight 285.3443
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

PF-06651600 is a newly discovered irreversible covalent JAK3-selective inhibitor. A high level of selectivity towards JAK3 is achieved by the covalent interaction of PF-06651600 with a unique cysteine residue (Cys-909) in the catalytic domain of JAK3, which is replaced by a serine residue in the other JAK isoforms. PF-06651600 allowed the comparison of JAK3-selective inhibition to pan-JAK or JAK1-selective inhibition, in relevant immune cells to a level that could not be achieved previously without such potency and selectivity. In vitro, PF-06651600 inhibits Th1 and Th17 cell differentiation and function, and in vivo it reduces disease pathology in rat adjuvant-induced arthritis as well as in mouse experimental autoimmune encephalomyelitis models. Preclinical data demonstrates that inhibition of the cytolytic function of CD8+ T cells and NK cells by PF-06651600 is driven by the inhibition of TEC kinases. Based on the underlying pathophysiology of inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, alopecia areata and vitiligo, the dual activity of PF06651600 towards JAK3 and the TEC kinase family may provide a beneficial inhibitory profile for therapeutic intervention. PF-06651600 is in phase III clinical trial for the treatment of alopecia areata and in phase II clinical trial for the treatment of Crohn's disease, Rheumatoid arthritis, Ulcerative colitis and Vitiligo.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.346 nM [IC50]
1638.0 nM [IC50]
1507.0 nM [IC50]
3779.0 nM [IC50]
PubMed

PubMed

TitleDatePubMed

Sample Use Guides

In Vivo Use Guide
Curator's Comment: Mice data
Single administration - 30 mg/kg
Route of Administration: Oral
Substance Class Chemical
Created
by admin
on Sat Dec 16 17:42:49 UTC 2023
Edited
by admin
on Sat Dec 16 17:42:49 UTC 2023
Record UNII
2OYE00PC25
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RITLECITINIB
INN  
Official Name English
Ritlecitinib [WHO-DD]
Common Name English
ritlecitinib [INN]
Common Name English
PF-06651600
Code English
2-PROPEN-1-ONE, 1-((2S,5R)-2-METHYL-5-(7H-PYRROLO(2,3-D)PYRIMIDIN-4-YLAMINO)-1-PIPERIDINYL)-
Common Name English
Code System Code Type Description
INN
11170
Created by admin on Sat Dec 16 17:42:50 UTC 2023 , Edited by admin on Sat Dec 16 17:42:50 UTC 2023
PRIMARY
DRUG BANK
DB14924
Created by admin on Sat Dec 16 17:42:50 UTC 2023 , Edited by admin on Sat Dec 16 17:42:50 UTC 2023
PRIMARY
SMS_ID
300000010803
Created by admin on Sat Dec 16 17:42:50 UTC 2023 , Edited by admin on Sat Dec 16 17:42:50 UTC 2023
PRIMARY
CAS
1792180-81-4
Created by admin on Sat Dec 16 17:42:50 UTC 2023 , Edited by admin on Sat Dec 16 17:42:50 UTC 2023
PRIMARY
FDA UNII
2OYE00PC25
Created by admin on Sat Dec 16 17:42:50 UTC 2023 , Edited by admin on Sat Dec 16 17:42:50 UTC 2023
PRIMARY
NCI_THESAURUS
C161783
Created by admin on Sat Dec 16 17:42:50 UTC 2023 , Edited by admin on Sat Dec 16 17:42:50 UTC 2023
PRIMARY
PUBCHEM
118115473
Created by admin on Sat Dec 16 17:42:50 UTC 2023 , Edited by admin on Sat Dec 16 17:42:50 UTC 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
JAK3-Selective Inhibition over pan-JAK or JAK1-Selective Inhibition
IRREVERSIBLE INHIBITOR
IC50
TARGET -> INHIBITOR
IRREVERSIBLE INHIBITOR
k(inactivation)
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
IRREVERSIBLE INHIBITOR
kinact/Ki
Related Record Type Details
ACTIVE MOIETY