upadacitinib   Click here for help

GtoPdb Ligand ID: 9246

Synonyms: ABT-494 | Rinvoq®
Approved drug Immunopharmacology Ligand
upadacitinib is an approved drug (EMA & FDA (2019))
Compound class: Synthetic organic
Comment: Upadacitinib (ABT-494) is a novel second generation orally active Janus kinase inhibitor with high JAK1 selectivity [5,10]. The chemical structure is claimed as compound 1 in Abbvie's patent WO2015061665 [10]. It was developed for potential clinical efficacy in multiple autoimmune diseases. Its first approval was for the treatment of rheumatoid arthritis [2].
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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 5
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 78.32
Molecular weight 380.16
XLogP 3.06
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 CCC1CN(CC1c1cnc2n1c1cc[nH]c1nc2)C(=O)NCC(F)(F)F
Isomeric SMILES CC[C@@H]1CN(C[C@@H]1c1cnc2n1c1cc[nH]c1nc2)C(=O)NCC(F)(F)F
InChI InChI=1S/C17H19F3N6O/c1-2-10-7-25(16(27)24-9-17(18,19)20)8-11(10)13-5-22-14-6-23-15-12(26(13)14)3-4-21-15/h3-6,10-11,21H,2,7-9H2,1H3,(H,24,27)/t10-,11+/m1/s1
InChI Key WYQFJHHDOKWSHR-MNOVXSKESA-N
Immunopharmacology Comments
Upadacitinib (ABT-494) is reported to have met all of its primary and secondary endpoints in Phase 3 clinical trial in patients with DMARD refactory moderate to severe rheumatoid arthritis (RA), or with DMARD intolerance- see this drugs.com webpage report for further details [11]. Abbvie published an online update in April 2018, reporting that a significantly higher proportion of patients given upadacitinib achieved clinical remission compared to placebo controls, and that upadacitinib was more effective in achieving a low disease activity score compared to adalimumab [1].
Immunopharmacology Disease
Disease X-Refs Comment References
Crohn's disease Disease Ontology: DOID:8778
OMIM: 266600
Orphanet: ORPHA206
 Phase 3 clinical candidate for CD.
Rheumatoid arthritis Disease Ontology: DOID:7148
OMIM: 180300
 FDA approved drug for RA (August 2019).
Temporal arteritis Disease Ontology: DOID:13375
OMIM: 187360
Orphanet: ORPHA397
 Phase 3 clinical candidate for temporal arteritis (giant cell arteritis)- see NCT03725202
Psoriatic arthritis Disease Ontology: DOID:9008
 Phase 3 clinical candidate for PsA- see NCT03104374
Ulcerative colitis Disease Ontology: DOID:8577
OMIM: 266600
Orphanet: ORPHA771
 Phase 3 clinical candidate for UC- see NCT02819635
Atopic dermatitis Disease Ontology: DOID:3310
OMIM: 603165
 Phase 3 clinical candidate for AD- see NCT03568318