General
Preferred name
ML154
Synonyms
CHEMBL1474387 ()
ML 154 ()
ML155 ()
NCGC84 ()
NCGC 84 ()
ML-154 ()
P&D ID
PD015982
CAS
1345964-89-7
1346105-73-4
Tags
available
probe
Probe info
Probe selectivity
protein-selective
Probe type
P&D approved
calculated probe
experimental probe
Probe sources
Chemical Probes.org
High-quality chemical probes
MLP Probes
Tool Compound Set
Probe targets
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
DESCRIPTION The probe is able to inhibit the hydrolytic activity of the N370S mutant form of glucocerebrosidase, as well as wild type glucocerebrosidase, in tissue homogenate assays. The probe does not inhibit purified glucocerebrosidase, but the cellular activity of the enzyme is known to be dependent on interactions with other factors, such as Saposin C. Importantly, the probe increased glucocerebrosidase translocation to the lysosome in Gaucher patient-derived fibroblasts homozygous for the N370S mutation, and can be used to study ER-lysosomal trafficking of clinically relevant GC mutants in vitro. This probe may be a useful lead for the clinical development of a chemical chaperone of glucocerebrosidase.
DESCRIPTION There is a clear need to discover novel small molecule antagonists of the Neuropeptide S Receptor (NPSR) to help probe NPS/NPSR pharmacology and to validate the importance of this neurocircuitry in animal models. SHA68, a compound disclosed by Takeda Pharmaceutical Company, shows only 50% efficacy in an in vivo hyperlocomotion mouse model. An additional chemotype disclosed by Merck shows ex vivo receptor occupancy in discrete regions of the rat brain after intraperitoneal (IP) dosing. However, no small molecule has yet demonstrated robust in vivo efficacy in multiple animal models.
DESCRIPTION NCGC 84 is a competitive, selective, and brain penetrant NPS receptor antagonist . We show the parent molecule, which is used experimentally as the bromide (PubChem CID 46930969). (GtoPdb)
DESCRIPTION There is a clear need to discover novel small molecule antagonists of the Neuropeptide S Receptor (NPSR) to help probe NPS/NPSR pharmacology and to validate the importance of this neurocircuitry in animal models. SHA68, a compound disclosed by Takeda Pharmaceutical Company, shows only 50% efficacy in an in vivo hyperlocomotion mouse model. An additional chemotype disclosed by Merck shows ex vivo receptor occupancy in discrete regions of the rat brain after intraperitoneal (IP) dosing. However, no small molecule has yet demonstrated robust in vivo efficacy in multiple animal models. (MLP Probes)
MOA Antagonist (Chemical Probes.org)
DESCRIPTION Endogenous adrenergic hormone and neurotransmitter (Tocris Bioactive Compound Library)
DESCRIPTION ML 154 is a neuropeptide S receptor antagonist. It has the potential to be used in the treatment of sleep, anxiety and addiction disorders. (BOC Sciences Bioactive Compounds)
Compound Sets
15
Axon Medchem Screening Library
2321
BOC Sciences Bioactive Compounds
ml-154-cas-1345964-89-7-item-169441
Cayman Chemical Bioactives
30200
Chemical Probes.org
ml154
Concise Guide to Pharmacology 2017/18
9168
Concise Guide to Pharmacology 2019/20
9168
Concise Guide to Pharmacology 2021/22
9168
Guide to Pharmacology
9168
High-quality chemical probes
PD015982
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL1474387
MedChem Express Bioactive Compound Library
HY-108626
MLP Probes
NBK51966
Tocris Bioactive Compound Library
5161
Tool Compound Set
ZINC Tool Compounds
ZINC000038142424
External IDs
22
Properties
(calculated by RDKit )
Molecular Weight
465.15
Hydrogen Bond Acceptors
2
Hydrogen Bond Donors
0
Rotatable Bonds
6
Ring Count
5
Aromatic Ring Count
5
cLogP
5.0
TPSA
9.03
Fraction CSP3
0.07
Chiral centers
0.0
Largest ring
6.0
QED
0.25
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Antitarget
V1B Vasopressin Receptor
Alphaglucosidase
Target
NPSR
neuropeptide S receptor
N370S Glucocerebrosidase
NPS antagonist
NPSR1
Primary Target
Neuropeptide S Receptors
MOA
Antagonist
Target class
GPCR
Target subclass
Neuropeptide S Receptor
Source data