ritlecitinib   

GtoPdb Ligand ID: 9559

Synonyms: compound 11 [PMID: 28139931] | example 5 [WO2015083028] | PF-06651600 | PF06651600
Compound class: Synthetic organic
Comment: Ritlecitinib (PF-06651600) is a potent, orally active, selective covalent inhibitor of Janus kinase 3 (JAK3) [3], with anti-inflammatory activity in in vivo models [2]. It is example 5 in a Pfizer patent that provides SAR for 343 analogues [1]. There are three crystal structures available for compounds reported in [3] with JAK3, but not for compound 11 (the PDB identifiers are 5TTV, 5TTU and 5TTS).

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Click here for structure editor
Physico-chemical Properties

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 4
Topological polar surface area 73.91
Molecular weight 285.16
XLogP 1.92
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES C=CC(=O)N1CC(CCC1C)Nc1ncnc2c1cc[nH]2
Isomeric SMILES C=CC(=O)N1C[C@@H](CC[C@@H]1C)Nc1ncnc2c1cc[nH]2
InChI 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
InChI Key CBRJPFGIXUFMTM-WDEREUQCSA-N
Bioactivity Comments
PF-06651600 exhibits favourable selectivity against a screening panel of 305 kinases in vitro, and shows measurable inhibition of 7 of the 10 other kinases which share a cysteine residue analogous to Cys-909 in the JAK3 ATP binding site (these were BMX, ITK, TXK, TEC, BTK, BLK and HER4) [3].
ATP concentration for JAK3 is 4 μM at Km and for JAK1 is 40 μM at Km, but some assays reported in [3] were carried out at 1 mM ATP .
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
Janus kinase 3 Hs Inhibitor Inhibition 9.5 pIC50 -
⤷ pIC50 9.5 (IC50 3x10-10 M)
Description: At 4 μM ATP (Km).
Janus kinase 1 Hs Inhibitor Inhibition 5.8 pIC50 - 3
⤷ pIC50 5.8 (IC50 1.64x10-6 M) [3]
Description: At 1 mM ATP.