ARRY-371797   Click here for help

GtoPdb Ligand ID: 11095

Synonyms: ARRY-797 | ARRY371797 | ARRY797 | compound 7 [PMID: 19950901]
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: ARRY-371797 is a clinical stage, oral, p38α (MAPK14)-selective kinase inhibitor that was originally developed by Array BioPharma (a Pfizer owned company since mid-2019) for anti-inflammatory and analgesic potential [2]. However, development for chronic inflammatory diseases has since been terminated. No results from completed analgesia trials have been published. Subsequent repositioning has seen the focus transfer to ARRY-371797 for LMNA-related dilated cardiomyopathy. p38α signalling is hyperactivated in mice with cardiomyopathy caused by lamin A/C gene (LMNA) mutation [3] and p38α activation is observed in the hearts from human subjects with LMNA-related dilated cardiomyopathy, thus ARRY-371797 has been advanced as a therapeutic option for this indication.
Click here for help

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.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

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.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

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.

✖
Hydrogen bond acceptors 4
Hydrogen bond donors 1
Rotatable bonds 9
Topological polar surface area 59.39
Molecular weight 416.2
XLogP 4.09
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help

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.

✖
Canonical SMILES CN(CCNC(=O)c1cc2c(cc1Oc1ccc(cc1F)F)cnn2CC(C)C)C
Isomeric SMILES CN(CCNC(=O)c1cc2c(cc1Oc1ccc(cc1F)F)cnn2CC(C)C)C
InChI InChI=1S/C22H26F2N4O2/c1-14(2)13-28-19-11-17(22(29)25-7-8-27(3)4)21(9-15(19)12-26-28)30-20-6-5-16(23)10-18(20)24/h5-6,9-12,14H,7-8,13H2,1-4H3,(H,25,29)
InChI Key IFGWYHGYNVGVRB-UHFFFAOYSA-N
References
1. Bouhaddou M, Memon D, Meyer B, White KM, Rezelj VV, Marrero MC, Polacco BJ, Melnyk JE, Ulferts S, Kaake RM. (2020)
The Global Phosphorylation Landscape of SARS-CoV-2 Infection.
Cell, Article Online Now. DOI: 10.1016/j.cell.2020.06.034
2. Goldstein DM, Kuglstatter A, Lou Y, Soth MJ. (2010)
Selective p38alpha inhibitors clinically evaluated for the treatment of chronic inflammatory disorders.
J Med Chem, 53 (6): 2345-53. [PMID:19950901]
3. Muchir A, Wu W, Choi JC, Iwata S, Morrow J, Homma S, Worman HJ. (2012)
Abnormal p38α mitogen-activated protein kinase signaling in dilated cardiomyopathy caused by lamin A/C gene mutation.
Hum Mol Genet, 21 (19): 4325-33. [PMID:22773734]