OICR-9429 Property

Boiling point:

693.0±55.0 °C(Predicted)

Density 

1.325±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

insoluble in EtOH; insoluble in H2O; ≥21.52 mg/mL in DMSO

form 

powder

pka

8.84±0.10(Predicted)

color 

white to light brown

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P321Specific treatment (see … on this label).

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

OICR-9429 Chemical Properties,Usage,Production

Uses

OICR-9429 is a chemical probe which inhibits the interaction of WDR5 (WD-repeat Protein 5) with peptide regions of MLL and Histone 3 with high selectivity. WDR5 is a part of the mixed-lineage leukemia (MLL) transferase complex that targets histone 3.

Biological Activity

oicr-9429 is an antagonist of wdr5-mll interaction.wdr5 has been identified as a component of the mll complex, which is required for histone h3 tri-methylation by its binding of histone h3. thus, wdr5 is reported to be a presenter component of mll, suggesting that wdr5 can bind substrates of methylated histone h3 to the mll complex for further methylation.

Biochem/physiol Actions

OICR-9429 is a cell penetrant, potent and selective antagonist of the interaction of WDR5 (WD repeat domain 5) with peptide regions of MLL and Histone 3 that potently binds to WDR5. OICR-9429 inhibits the interaction of WDR5 with MLL1 and RbBP5 in cells. For full characterization details, please see OICR-9429 on the Structural Genomics Consortium (SGC) website.OICR-0547 is the negative control for the active probe, OICR-9429. To request a sample of the negative control from the SGC, click here.To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc

in vitro

previous study found that wdr5 could be detected readily in c/ebpα immunoprecipitates from lysates of cebpap30/p30 cells by the treatment of oicr-9429, indicating that the wdr5-mll interaction could not influence p30 binding. moreover, the gene expression profiling of oicr-9429-treated cebpap30/p30 cells showed that wdr5 antagonism could result in the upregulation of myeloid-specific transcripts. in addition, the gene set enrichment analyses demonstrated a close correlation between oicr-9429–induced genes and genes that were upregulated after wdr5 knockdown. furthermore, the gene profile of cebpap30/p30 lics6 was downregulated due to the wdr5 antagonism caused by oicr-9429. further treatment of oicr-9429 to cebpap30/p30 cells was found to be associated with myeloid differentiation and loss of progenitor morphology [1].

IC 50

5 um

storage

Store at -20°C

References

[1] FLORIAN GREBIEN. Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia[J]. Nature chemical biology, 2015, 11 8: 571-578. DOI:10.1038/nchembio.1859.
[2] DONG A, DOMBROVSKI L, WALKER J, et al. Crystal structure of human WDR5 in complex with compound OICR-9429[C]. 2014: 0. DOI:10.2210/pdb4ql1/pdb.
[3] MATTH?US GETLIK. Structure-Based Optimization of a Small Molecule Antagonist of the Interaction Between WD Repeat-Containing Protein 5 (WDR5) and Mixed-Lineage Leukemia 1 (MLL1)[J]. Journal of Medicinal Chemistry, 2016, 59 6: 2478-2496. DOI:10.1021/acs.jmedchem.5b01630.