General
Preferred name
GNE-049
Synonyms
9UD ()
cpd 10 ()
1-{3-[7-(difluoromethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1,2,3,4-tetrahydroquinolin-1-yl]-1-(oxan-4-yl)-1H,4H,5H,6H,7H-pyrazolo[4,3-c]pyridin-5-yl}ethan-1-one ()
P&D ID
PD102627
CAS
1936421-41-8
Tags
available
probe
Probe info
Probe type
P&D approved
experimental probe
Probe selectivity
family-selective
Probe sources
Chemical Probes.org
High-quality chemical probes
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)
COMMENT GNE-049 has been studied in various cellular assays and is a potent, selective, cell-penetrant probe. It has also been evaluated in preliminary PK studies in 4 species (mouse, rat, dog, cyno) and studied in preliminary high dose rat TK up to 250 mg/kg, at which dose adverse CNS-related signs were observed. Kpuu 3h post dose was 0.43. A second probe, GNE-781 (cpd 19 in the same paper) has a similar profile to GNE-049, but with higher polar surface area and no CNS penetration. Both probes are high quality, the 2nd probe GNE-781 has more published in vivo data, and unless there is a need for CNS penetration, then should be used in preference to this probe GNE-049. However, both are high quality probes. Mar 24 2021 - 10:07am
DESCRIPTION GNE-049 is a highly potent and selective CBP inhibitor with an IC50 of 1.1 nM in TR-FRET assay. GNE-049 also inhibits BRET and BRD4(1) with IC50s of 12 nM and 4200 nM, respectively[1].
DESCRIPTION GNE-049 is a small molecule inhibitor of the CREB binding protein (CBP) bromodomain , but spares the BRD4(1) bromodomain. It has been used in the design of CBP/p300 PROTAC degraders . (GtoPdb)
MOA Inhibitor (Chemical Probes.org)
DESCRIPTION GNE-049 is a highly potent and selective histone lysine acetyltransferase CREBBP inhibitor with an IC50 of 1.1 nM. It also inhibits BRD4(1) (Bromodomain-containing protein 4 isoform long, bromodomain 1) with IC50 = 4.2 µM. (Enamine Bioactive Compounds)
Cell lines
2
Organisms
0
Compound Sets
10
Chemical Probes.org
gne-049
CZ-OPENSCREEN Bioactive Library
Enamine Bioactive Compounds
EBC-12884
Enamine BioReference Compounds
EUbOPEN Chemogenomics Library
EUB0002238
Guide to Pharmacology
13247
High-quality chemical probes
PD102627
Mcule NIBR MoA Box Subset
MCULE-3884400615
MedChem Express Bioactive Compound Library
HY-108435
Novartis Chemogenetic Library (NIBR MoA Box)
External IDs
9
Properties
(calculated by RDKit )
Molecular Weight
510.26
Hydrogen Bond Acceptors
7
Hydrogen Bond Donors
0
Rotatable Bonds
4
Ring Count
6
Aromatic Ring Count
3
cLogP
4.56
TPSA
68.42
Fraction CSP3
0.52
Chiral centers
0.0
Largest ring
6.0
QED
0.51
Structural alerts
0
No structural alerts detected
Custom attributes
(extracted from source data)
Member status
member
Target subclass
Bromodomain
Bromodomain, Bromodomain
Target class
Epigenetics
Epigenetic, Epigenetic
Orthogonal probe
CPI-1612
Target
CREBBP, EP300
Epigenetic Reader Domain
Histone Acetyltransferase
Recommended Cell Concentration
None
Source data