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Details

Stereochemistry ABSOLUTE
Molecular Formula C15H19N5O.C3H4O4
Molecular Weight 389.4057
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RITLECITINIB MALONATE

SMILES

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

InChI

InChIKey=QMPMPSGDPRHZCG-VZXYPILPSA-N
InChI=1S/C15H19N5O.C3H4O4/c1-3-13(21)20-8-11(5-4-10(20)2)19-15-12-6-7-16-14(12)17-9-18-15;4-2(5)1-3(6)7/h3,6-7,9-11H,1,4-5,8H2,2H3,(H2,16,17,18,19);1H2,(H,4,5)(H,6,7)/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

Molecular Formula C3H4O4
Molecular Weight 104.0615
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
Design of a Janus Kinase 3 (JAK3) Specific Inhibitor 1-((2S,5R)-5-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one (PF-06651600) Allowing for the Interrogation of JAK3 Signaling in Humans.
2017 Mar 9

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 09:04:27 GMT 2023
Edited
by admin
on Sat Dec 16 09:04:27 GMT 2023
Record UNII
132LF5WGH4
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RITLECITINIB MALONATE
Common Name English
1-((2S,5R)-2-METHYL-5-(7H-PYRROLO(2,3-D)PYRIMIDIN-4-YLAMINO)-1-PIPERIDINYL)-2-PROPEN-1-ONE MALONATE
Systematic Name English
PROPANEDIOIC ACID, COMPD. WITH 1-((2S,5R)-2-METHYL-5-(7H-PYRROLO(2,3-D)PYRIMIDIN-4-YLAMINO)-1-PIPERIDINYL)-2-PROPEN-1-ONE (1:1)
Systematic Name English
PF-06651600 MALONATE
Code English
Code System Code Type Description
PUBCHEM
124203830
Created by admin on Sat Dec 16 09:04:28 GMT 2023 , Edited by admin on Sat Dec 16 09:04:28 GMT 2023
PRIMARY
FDA UNII
132LF5WGH4
Created by admin on Sat Dec 16 09:04:28 GMT 2023 , Edited by admin on Sat Dec 16 09:04:28 GMT 2023
PRIMARY
CAS
2140301-97-7
Created by admin on Sat Dec 16 09:04:28 GMT 2023 , Edited by admin on Sat Dec 16 09:04:28 GMT 2023
PRIMARY
SMS_ID
300000045439
Created by admin on Sat Dec 16 09:04:28 GMT 2023 , Edited by admin on Sat Dec 16 09:04:28 GMT 2023
PRIMARY
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ACTIVE MOIETY