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
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
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2148 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27791347 |
0.346 nM [IC50] | ||
Target ID: CHEMBL2835 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27791347 |
1638.0 nM [IC50] | ||
Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27791347 |
1507.0 nM [IC50] | ||
Target ID: CHEMBL3553 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27791347 |
3779.0 nM [IC50] |
PubMed
Title | Date | PubMed |
---|---|---|
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 |
|
PF-06651600, a Dual JAK3/TEC Family Kinase Inhibitor. | 2019 Jun 21 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/31082193
Curator's Comment: Mice data
Single administration - 30 mg/kg
Route of Administration:
Oral
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 09:04:27 GMT 2023
by
admin
on
Sat Dec 16 09:04:27 GMT 2023
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Record UNII |
132LF5WGH4
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Record Status |
Validated (UNII)
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Record Version |
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132LF5WGH4
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2140301-97-7
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300000045439
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PARENT -> SALT/SOLVATE |
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ACTIVE MOIETY |