NIK SMI1   Click here for help

GtoPdb Ligand ID: 9964

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: NIK SMI1 is a selective inhibitor of the NF-κB-inducing kinase, NIK (MAP3K14) [1]. NIK is a kinase that operates downstream of several TNF family receptors, including BAFF (TNFRSF13C), TWEAK (TNFRSF12A), CD40 (TNFRSF5), and OX40 (TNFRSF4), and which mediates non-canonical NF-κB signaling. Inhibition of NIK recapitulates the inhibition of BAFF that is observed for example using the anti-BAFF, SLE approved biologic belimumab. The compound has no effect on canonical NF-κB signaling.
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 6
Hydrogen bond donors 2
Rotatable bonds 3
Topological polar surface area 105.75
Molecular weight 365.14
XLogP 1.39
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 COc1cc(nc(c1)c1cccc(c1)C#CC1(O)CCN(C1=O)C)C(=O)N
Isomeric SMILES COc1cc(nc(c1)c1cccc(c1)C#C[C@]1(O)CCN(C1=O)C)C(=O)N
InChI InChI=1S/C20H19N3O4/c1-23-9-8-20(26,19(23)25)7-6-13-4-3-5-14(10-13)16-11-15(27-2)12-17(22-16)18(21)24/h3-5,10-12,26H,8-9H2,1-2H3,(H2,21,24)/t20-/m0/s1
InChI Key LQSHXYHWYGKAMX-FQEVSTJZSA-N
Bioactivity Comments
In a screening panel NIK SMI1 inhibited just 3 off-target kinases, KHS1 (MAP4K5), LRRK2, and PKD1 (PRKD1), by >75% at 1 μM, out of 222 kinases tested. Ki determination established NIK SMI1's selectivity over these off-targets [1].
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
mitogen-activated protein kinase kinase kinase 14 Primary target of this compound Hs Inhibitor Inhibition 9.6 pKi - 1
⤷ pKi 9.6 (Ki 2.3x10-10 M) [1]
mitogen-activated protein kinase kinase kinase 14 Mm Inhibitor Inhibition 9.4 pKi - 1
⤷ pKi 9.4 (Ki 3.95x10-10 M) [1]
mitogen-activated protein kinase kinase kinase kinase 5 Hs Inhibitor Inhibition 7.3 pKi - 1
⤷ pKi 7.3 (Ki 4.96x10-8 M) [1]
protein kinase D1 Hs Inhibitor Inhibition 7.1 pKi - 1
⤷ pKi 7.1 (Ki 7.52x10-8 M) [1]
leucine rich repeat kinase 2 Hs Inhibitor Inhibition 6.6 pKi - 1
⤷ pKi 6.6 (Ki 2.478x10-7 M) [1]