OICR-9429

OICR-9429 A chemical probe for WDR5

This probe is available from Cayman Chemical , Tocris and Sigma-Aldrich.

The control may be requested by clicking here.

  • overview
  • properties
  • selectivity profile
  • cell based assay data
  • references
  • co-crystal structures
overview

A collaboration between the SGC and The Drug Discovery Program at the Ontario Institute for Cancer Research (OICR) has resulted in the discovery of OICR-9429, a chemical probe for WDR5, a component of several chromatin regulatory complexes including the MLL1 (Mixed Lineage Leukemia 1) complex. OICR-9429 is a potent antagonist of the interaction of WDR5 with peptide regions of MLL and Histone 3 with >100-fold selectivity over other chromatin “reader” domains, methyltransferases, and other non-epigenetic targets. OICR-9429 has been shown to bind to WDR5 with KD values of 24 nM (Biacore) and 52 nM (ITC). OICR-9429 also disrupts the interaction of WDR5 with MLL1 and RbBP5 in cells with IC50 values below 1 µM.

A closely-related compound, OICR-0547, does not show WDR5 antagonism, and can therefore be used as a negative control in phenotypic assays.

properties


OICR-9429


OICR-0547
(negative control)

 

Physical and chemical properties for OICR-9429
Molecular weight555.2
Molecular formulaC29H32F3N5O3
IUPAC name5-((2-(4-methyl-piperazin-1-yl)-5-(3-((morpholin-4-yl)-methyl)-phenyl)-phenylamino)-formyl)-4-(trifluoro-methyl)-1,2-dihydro-pyridin-2-one
MollogP3.382
PSA65.34
No. of chiral centres0
No. of rotatable bonds8
No. of hydrogen bond acceptors7
No. of hydrogen bond donors2



 

Physical and chemical properties for OICR-0547 (Negative Control)
Molecular weight542.2
Molecular formulaC28H29F3N4O4
IUPAC name5-((2-(morpholin-4-yl)-5-(3-((morpholin-4-yl)-methyl)-phenyl)-phenylamino)-formyl)-4-(trifluoro-methyl)-1,2-dihydro-pyridin-2-one
MollogP3.331
PSA69.77
No. of chiral centres0
No. of rotatable bonds8
No. of hydrogen bond acceptors7
No. of hydrogen bond donors2
  • SMILES:
  • OICR-9429: CN1CCN(CC1)c1ccc(cc1NC(C1=CNC(C=C1C(F)(F)F)=O)=O)c1cccc(CN2CCOCC2)c1
  • OICR-0547: C1COCCN1Cc1cccc(c1)c1ccc(c(c1)NC(C1=CNC(C=C1C(F)(F)F)=O)=O)N1CCOCC1
  • InChI:
  • OICR-9429: InChI=1S/C29H32F3N5O3/c1-35-7-9-37(10-8-35)26-6-5-22(21-4-2-3-20(15-21)19-36-11-13-40-14-12-36)16-25(26)34-28(39)23-18-33-27(38)17-24(23)29(30,31)32/h2-6,15-18H,7-14,19H2,1H3,(H,33,38)(H,34,39)
  • OICR-0547: InChI=1S/C28H29F3N4O4/c29-28(30,31)23-16-26(36)32-17-22(23)27(37)33-24-15-21(4-5-25(24)35-8-12-39-13-9-35)20-3-1-2-19(14-20)18-34-6-10-38-11-7-34/h1-5,14-17H,6-13,18H2,(H,32,36)(H,33,37)
  • InChIKey:
  • OICR-9429: DJOVLOYCGXNVPI-UHFFFAOYSA-N
  • OICR-0547: RFHOOFYUTGZPFH-UHFFFAOYSA-N
selectivity profile

in vitro potency
cell based assay data

references

Pharmacological targeting of the Wdr5-MLL interaction in C/EBPa N-terminal leukemia ,Florian Grebien, Masoud Vedadi, Matthäus Getlik, Roberto Giambruno, Amit Grover, Roberto Avellino, Anna Skucha, Sarah Vittori, Ekaterina Kuznetsova, David Smil, Dalia Barsyte-Lovejoy, Fengling Li, Gennadiy Poda, Matthieu Schapira, Hong Wu, Aiping Dong, Guillermo Senisterra, Alexey Stukalov, Kilian V M Huber,Andreas Schönegger, Richard Marcellus, Martin Bilban, Christoph Bock, Peter J Brown, Johannes Zuber, Keiryn L Bennett, Rima Al-awar, Ruud Delwel, Claus Nerlov, Cheryl H Arrowsmith & Giulio Superti-Furga. Nature Chemical Biology. 10.1038/nchembio.1859

pk properties
co-crystal structures

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Main features

synthetic schemes
materials and methods
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