lorpucitinib   Click here for help

GtoPdb Ligand ID: 10631

Synonyms: compound 2 [PMID: 32134643] | example 1 [WO2018112379A1] | JNJ-64251330 | JNJ64251330
Compound class: Synthetic organic
Comment: The chemical structure that was submitted to the WHO for the INN lorpucitinib is identical to the structure of example 1 that is claimed as a pan-Janus kinase inhibitor in Janssen's patent WO2018112379A1 [1]. Based on structural conformation this is an exact match to PubChem SID 395564298, and this is associated to CID 134611548. However, this CID does not specify the stereochemical conformation as described in the patent or as stipulated in the INN submission. The chemical structure was disclosed in March 2020 as a JAK inhibitor that is intended for the treatment of inflammatory bowel disease [2]. Its activity is restricted to the gut by virtue of its permeability and physicochemical properties, and this limits systemic exposure and the potential for on-target adverse events. Lorpucitinib is Janssen's clinical lead JNJ-64251330. It blocks phosphorylation and activation of Signal Transducer and Activator of Transcription (STAT) factor proteins.
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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
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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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Physico-chemical Properties
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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 6
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 119.62
Molecular weight 408.23
XLogP 1.79
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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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 N#CCC1CCC(CC1)n1c(CC(=O)NCC(O)(C)C)nc2c1c1cc[nH]c1nc2
Isomeric SMILES N#CC[C@@H]1CC[C@H](CC1)n1c(CC(=O)NCC(O)(C)C)nc2c1c1cc[nH]c1nc2
InChI InChI=1S/C22H28N6O2/c1-22(2,30)13-26-19(29)11-18-27-17-12-25-21-16(8-10-24-21)20(17)28(18)15-5-3-14(4-6-15)7-9-23/h8,10,12,14-15,30H,3-7,11,13H2,1-2H3,(H,24,25)(H,26,29)/t14-,15-
InChI Key NJKMSBSVJSQUBU-SHTZXODSSA-N
References
1. Koudriakova T, Kreutter K, Leonard K, Rizzolio M, Smith RC, Tichenor MS, Wang A. (2018)
Small molecule inhibitors of the JAK family of kinases.
Patent number: WO2018112379A1. Assignee: Janssen Pharmaceutica. Priority date: 16/12/2016. Publication date: 21/06/2018.
2. Leonard KA, Madge LA, Krawczuk PJ, Wang A, Kreutter KD, Bacani GM, Chai W, Smith RC, Tichenor MS, Harris MC et al.. (2020)
Discovery of a Gut-Restricted JAK Inhibitor for the Treatment of Inflammatory Bowel Disease.
J Med Chem, 63 (6): 2915-2929. [PMID:32134643]