NB-360   Click here for help

GtoPdb Ligand ID: 9822

Synonyms: NB360
PDB Ligand
Compound class: Synthetic organic
Comment: Due to good brain penetration, oral doses of Novartis NB-360 completely block amyloid-β deposition in an APP transgenic mouse model [3]. Data across species suggest similar treatment effects can possibly be achieved in humans. The reduced neuroinflammation upon amyloid reduction by NB-360 treatment supports the notion that targeting amyloid-β pathology can have beneficial downstream effects on the progression of Alzheimer's disease. Note this inhibitor is equipotent against BACE2 in vitro. NB-360 did not progress to clinical development, but is suitable as an effective pharmacological tool to investigate the effects of BACE-1 inhibition in Alzherimer's disease models [2]. There is a recent paper describing impairment of synaptic plasticity in mice via Seizure Protein 6 [4]. One of the Novartis patents has a SAR set of 184 IC50 values [1].
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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 7
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 113.39
Molecular weight 449.15
XLogP 2.63
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#Cc1cnc(c(c1)C)C(=O)Nc1ccc(c(c1)C1(C)COC(C(=N1)N)(C)C(F)(F)F)F
Isomeric SMILES N#Cc1cnc(c(c1)C)C(=O)Nc1ccc(c(c1)[C@]1(C)CO[C@@](C(=N1)N)(C)C(F)(F)F)F
InChI InChI=1S/C21H19F4N5O2/c1-11-6-12(8-26)9-28-16(11)17(31)29-13-4-5-15(22)14(7-13)19(2)10-32-20(3,18(27)30-19)21(23,24)25/h4-7,9H,10H2,1-3H3,(H2,27,30)(H,29,31)/t19-,20+/m0/s1
InChI Key BQFHTVUWPJXLOW-VQTJNVASSA-N
Classification Click here for help
Compound class Synthetic organic
IUPAC Name Click here for help
N-[3-[(3R,6R)-5-amino-3,6-dimethyl-6-(trifluoromethyl)-2H-1,4-oxazin-3-yl]-4-fluorophenyl]-5-cyano-3-methylpyridine-2-carboxamide
Synonyms Click here for help
NB360
Database Links Click here for help
ChEMBL Ligand CHEMBL3261067
GtoPdb PubChem SID 354702293
PubChem CID 66665322
RCSB PDB Ligand SLK
Search Google for chemical match using the InChIKey BQFHTVUWPJXLOW-VQTJNVASSA-N
Search Google for chemicals with the same backbone BQFHTVUWPJXLOW
UniChem Compound Search for chemical match using the InChIKey BQFHTVUWPJXLOW-VQTJNVASSA-N
UniChem Connectivity Search for chemical match using the InChIKey BQFHTVUWPJXLOW-VQTJNVASSA-N