General
Preferred name
OICR-9429
Synonyms
OICR 9429 ()
GTPL8231 ()
AKOS025147341 ()
P&D ID
PD000011
CAS
1801787-56-3
Tags
available
probe
drug candidate
Drug indication
Discovery agent
Probe info
Probe type
calculated probe
experimental probe
Probe sources
Chemical Probes.org
High-quality chemical probes
Nature Chemical Biology Probes
Protein methyltransferases chemical toolbox
SGC 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)
COMMENT Recommended concentration is based on the finding that the IC50s for the disruption of WDR5-MLL and WDR5-RbBP5 complexes in co-IPs from HEK293 expressing Flag-WDR5 are 223 nM and 458 nM, respectively. Jun 12 2016 - 2:45pm; OICR-9429 is a small-molecule antagonist of the WDR5-MLL protein-protein interaction, a notoriously difficult class of molecular targets. There is solid evidence showing a direct in vitro interaction between OICR-9429 and its intended target, WDR5. This includes ITC and X-ray crystallography. This compound displays high affinity (Kd <100 nM) for WDR5. It has well-characterized, reversible binding kinetics. The authors also show (at least in vitro) that it does not significantly inhibit other many other HMTs, kinases or other pharmacologically relevant targets. There are convincing target-engagement data in cells via biotinylated pull-down proteomics and gene-expression profiling consistent with such engagement. It is effective in vitro versus p30-expressing cells. Note, there is <1-log difference is cytotoxicity of OICR-9429 to p30-expressing cells versus other cells, as reported in the original publication. Therefore, dosage of this probe should be carefully considered, perhaps even taking care to perform dose-response controls to rule out non-specific effects that may occur at higher compound concentrations. Users should take advantage of a close structural analog, OICR-0547, as a negative control compound. The authors present evidence showing the negative control compound does not disrupt the WDR5-MLL interaction in vitro. It has similar cytotoxoicity as OICR-9429 versus K562 cells. Users should also note that there is only ~1-log difference in cytotoxicity between the active compound and inactive analog. Jun 30 2016 - 4:17am
DESCRIPTION OICR-9429 was developed in a collaboration between the SGC (Structural Genomics Consortium) and The Drug Discovery Program at the Ontario Institute for Cancer Research (OICR). It can be used as a chemical probe for WDR5 activity, WDR5 being a component of several chromatin regulatory complexes including the MLL1 (mixed lineage leukemia 1) complex. OICR-9429 antagonises the interaction between WDR5 and MLL or Histone 3 binding domains. Click here to link to the SGC's full list of epigenetics probes. (GtoPdb)
DESCRIPTION OICR-9429 is high affinity WD repeat domain 5 (WDR5) inhibitor, competitively blocks WDR5 interaction with MLL protein via binding the central peptide-binding pocket of WDR5. OICR-9429 can suppress histone H3K4 trimethylation and can be used for the research of various cancers including non-MLL-rearranged leukaemia, colon, pancreatic, prostate cancer and bladder cancer (BCa) [1].
PRICE 119
MOA Antagonist (Chemical Probes.org)
DESCRIPTION Selective LIMK2 inhibitor; antitumor (Tocris Bioactive Compound Library)
DESCRIPTION High affinity and selective WDR5 antagonist (Tocriscreen Plus)
DESCRIPTION OICR-9429 is a potent antagonist of the interaction that WDR5 effect with peptide regions of MLL and Histone 3. It reduces the viability of acute myeloid leukemia cells in vitro. (TargetMol Bioactive Compound Library)
Cell lines
1
Organisms
0
Compound Sets
21
Cayman Chemical Bioactives
16095
Chemical Probes.org
oicr-9429
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugMAP
DMN7KPQ
EU-OPENSCREEN Bioactive Compound Library
EOS101144
EUbOPEN Chemogenomics Library
EUB0000211
Guide to Pharmacology
8231
High-quality chemical probes
PD000011
IPPI - DB
2240
MedChem Express Bioactive Compound Library
HY-16993
Nature Chemical Biology Probes
1859
Novartis Chemogenetic Library (NIBR MoA Box)
Protein methyltransferases chemical toolbox
ReFrame library
Selleckchem Bioactive Compound Library
oicr-9429
SGC Probes
OICR-9429
TargetMol Bioactive Compound Library
T6916
Tocris Bioactive Compound Library
5267
Tocriscreen Plus
5267
Tool Compound Set
External IDs
16
Properties
(calculated by RDKit )
Molecular Weight
555.25
Hydrogen Bond Acceptors
6
Hydrogen Bond Donors
2
Rotatable Bonds
6
Ring Count
5
Aromatic Ring Count
3
cLogP
3.9
TPSA
80.91
Fraction CSP3
0.38
Chiral centers
0.0
Largest ring
6.0
QED
0.48
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
Enzymes
Target
WD repeat-containing protein 5
Histone methyltransferase
WDR5
Apoptosis
Histone Methyltransferase,WDR5
Member status
member
MOA
WDR5 inhibitor
WDR5/MLL interaction inhibitor
Pathway
Angiogenesis
Chromatin/Epigenetic
JAK/STAT Signaling
Stem Cells
Tyrosine Kinase/Adaptors
Epigenetics
Protein Family
WD40
Target class
Structural protein
Target subclass
WD40-repeat proteins
Control
OICR-0547
Recommended Cell Concentration
1 uM
Source data