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MedKoo Cat#: 406821 | Name: OICR-9429
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

OICR-9429 is a potent and selective chemical probe suitable to help dissect the biological role of WDR5 (Kdisp < 100 nM). OICR-9429 selectively inhibited proliferation and induced differentiation in p30-expressing human AML cells. OICR-9429 disrupts the interaction of Wdr5 with MLL in cells, thereby selectively triggering a differentiation program in p30-expressing leukemia cells.

Chemical Structure

OICR-9429
OICR-9429
CAS#1801787-56-3

Theoretical Analysis

MedKoo Cat#: 406821

Name: OICR-9429

CAS#: 1801787-56-3

Chemical Formula: C29H32F3N5O3

Exact Mass: 555.2457

Molecular Weight: 555.60

Elemental Analysis: C, 62.69; H, 5.81; F, 10.26; N, 12.61; O, 8.64

Price and Availability

Size Price Availability Quantity
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 385.00 Ready to ship
100mg USD 685.00 Ready to ship
200mg USD 1,250.00 Ready to ship
500mg USD 2,450.00 Ready to ship
1g USD 3,850.00 2 weeks
2g USD 5,950.00 2 weeks
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Related CAS #
No Data
Synonym
OICR-9429; OICR 9429; OICR9429.
IUPAC/Chemical Name
N-(4-(4-methylpiperazin-1-yl)-3'-(morpholinomethyl)-[1,1'-biphenyl]-3-yl)-6-oxo-4-(trifluoromethyl)-1,6-dihydropyridine-3-carboxamide
InChi Key
DJOVLOYCGXNVPI-UHFFFAOYSA-N
InChi Code
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)
SMILES Code
O=C(C(C(C(F)(F)F)=C1)=CNC1=O)NC2=CC(C3=CC=CC(CN4CCOCC4)=C3)=CC=C2N5CCN(C)CC5
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
WD repeat-containing protein 5 (WDR5) is an important component of the multiprotein complex essential for activating mixed-lineage leukemia 1 (MLL1). Rearrangement of the MLL1 gene is associated with onset and progression of acute myeloid and lymphoblastic leukemias, and targeting the WDR5-MLL1 interaction may result in new cancer therapeutics. Our previous work showed that binding of small molecule ligands to WDR5 can modulate its interaction with MLL1, suppressing MLL1 methyltransferase activity.
Biological target:
OICR-9429 is a small-molecule antagonist of the Wdr5-MLL interaction with IC50 of 5 uM.
In vitro activity:
First this study tested whether OICR-9429 was able to disrupt the C/EBPα p30-Wdr5 interaction. Wdr5 was readily detected in C/EBPα immunoprecipitates from lysates of Cebpap30/p30 cells in the presence of OICR-9429, suggesting that the interaction of Wdr5 with MLL did not influence p30 binding (Supplementary Fig. 13). This study next tested the effect of OICR-9429 on Wdr5-dependent protein-protein interactions in cells using a biotinylated variant of the compound in a chemical proteomics experiment. Although this study was able to efficiently isolate Wdr5 using the biotinylated variant of OICR-9429, this enrichment was lost upon competition with excess unmodified OICR-9429 (Fig. 5a). Bioinformatic analysis of LC/MS/MS data revealed that Wdr5 was the primary target protein of OICR-9429 in cells (Fig. 5b). Notably, analysis did not identify any other components of SET/MLL HMT complexes, indicating that OICR-9429 disrupts integral protein-protein interactions between Wdr5 and its binding partners. Indeed, OICR-9429 reduced the amount of endogenous MLL and RBBP5 that coimmunoprecipitated with exogenously expressed Flag-tagged WDR5 in a dose-dependent manner (Fig. 5c). Reference: Nat Chem Biol. 2015 Oct;11(10):815. https://www.nature.com/articles/nchembio.1859
In vivo activity:
Protein levels of p16INK4a increased in IRI (ischemia reperfusion injury) mice following vehicle treatment compared with those in sham-operated mice, whereas they decreased in IRI mice with MM-102 or OICR-9429 injection (Figure 2a). Similarly, gene expression of p16INK4a also increased in IRI mice and was suppressed by MM-102 or OICR-9429 administration (Figure 2b). Meanwhile, expansion of the p16INK4a-positive area was observed mainly in the interstitial region of the kidney in IRI mice following vehicle treatment, but this area shrank with MM-102 treatment. Reference: Kidney Int. 2019 Nov;96(5):1162-1175. https://www.kidney-international.org/article/S0085-2538(19)30773-2/fulltext
Solvent mg/mL mM
Solubility
DMSO 10.0 18.00
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 555.60 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Grebien F, Vedadi M, Getlik M, Giambruno R, Grover A, Avellino R, Skucha A, Vittori S, Kuznetsova E, Smil D, Barsyte-Lovejoy D, Li F, Poda G, Schapira M, Wu H, Dong A, Senisterra G, Stukalov A, Huber KVM, Schönegger A, Marcellus R, Bilban M, Bock C, Brown PJ, Zuber J, Bennett KL, Al-Awar R, Delwel R, Nerlov C, Arrowsmith CH, Superti-Furga G. Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia. Nat Chem Biol. 2015 Aug;11(8):571-578. doi: 10.1038/nchembio.1859. Epub 2015 Jul 13. Erratum in: Nat Chem Biol. 2015 Oct;11(10):815. PMID: 26167872; PMCID: PMC4511833. 2. Neilsen BK, Chakraborty B, McCall JL, Frodyma DE, Sleightholm RL, Fisher KW, Lewis RE. WDR5 supports colon cancer cells by promoting methylation of H3K4 and suppressing DNA damage. BMC Cancer. 2018 Jun 20;18(1):673. doi: 10.1186/s12885-018-4580-6. PMID: 29925347; PMCID: PMC6011590. 3. Shimoda H, Doi S, Nakashima A, Sasaki K, Doi T, Masaki T. Inhibition of the H3K4 methyltransferase MLL1/WDR5 complex attenuates renal senescence in ischemia reperfusion mice by reduction of p16INK4a. Kidney Int. 2019 Nov;96(5):1162-1175. doi: 10.1016/j.kint.2019.06.021. Epub 2019 Aug 1. PMID: 31570196. 4. Zhou Q, Chen X, He H, Peng S, Zhang Y, Zhang J, Cheng L, Liu S, Huang M, Xie R, Lin T, Huang J. WD repeat domain 5 promotes chemoresistance and Programmed Death-Ligand 1 expression in prostate cancer. Theranostics. 2021 Mar 4;11(10):4809-4824. doi: 10.7150/thno.55814. PMID: 33754029; PMCID: PMC7978315.
In vitro protocol:
1. Grebien F, Vedadi M, Getlik M, Giambruno R, Grover A, Avellino R, Skucha A, Vittori S, Kuznetsova E, Smil D, Barsyte-Lovejoy D, Li F, Poda G, Schapira M, Wu H, Dong A, Senisterra G, Stukalov A, Huber KVM, Schönegger A, Marcellus R, Bilban M, Bock C, Brown PJ, Zuber J, Bennett KL, Al-Awar R, Delwel R, Nerlov C, Arrowsmith CH, Superti-Furga G. Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia. Nat Chem Biol. 2015 Aug;11(8):571-578. doi: 10.1038/nchembio.1859. Epub 2015 Jul 13. Erratum in: Nat Chem Biol. 2015 Oct;11(10):815. PMID: 26167872; PMCID: PMC4511833. 2. Neilsen BK, Chakraborty B, McCall JL, Frodyma DE, Sleightholm RL, Fisher KW, Lewis RE. WDR5 supports colon cancer cells by promoting methylation of H3K4 and suppressing DNA damage. BMC Cancer. 2018 Jun 20;18(1):673. doi: 10.1186/s12885-018-4580-6. PMID: 29925347; PMCID: PMC6011590.
In vivo protocol:
1. Shimoda H, Doi S, Nakashima A, Sasaki K, Doi T, Masaki T. Inhibition of the H3K4 methyltransferase MLL1/WDR5 complex attenuates renal senescence in ischemia reperfusion mice by reduction of p16INK4a. Kidney Int. 2019 Nov;96(5):1162-1175. doi: 10.1016/j.kint.2019.06.021. Epub 2019 Aug 1. PMID: 31570196. 2. Zhou Q, Chen X, He H, Peng S, Zhang Y, Zhang J, Cheng L, Liu S, Huang M, Xie R, Lin T, Huang J. WD repeat domain 5 promotes chemoresistance and Programmed Death-Ligand 1 expression in prostate cancer. Theranostics. 2021 Mar 4;11(10):4809-4824. doi: 10.7150/thno.55814. PMID: 33754029; PMCID: PMC7978315.
1: Getlik M, Smil D, Zepeda-Velázquez C, Bolshan Y, Poda G, Wu H, Dong A, Kuznetsova E, Marcellus R, Senisterra G, Dombrovski L, Hajian T, Kiyota T, Schapira M, Arrowsmith CH, Brown PJ, Vedadi M, Al-Awar R. 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 Med Chem. 2016 Mar 24;59(6):2478-96. doi: 10.1021/acs.jmedchem.5b01630. Epub 2016 Mar 9. PubMed PMID: 26958703. 2: Grebien F, Vedadi M, Getlik M, Giambruno R, Grover A, Avellino R, Skucha A, Vittori S, Kuznetsova E, Smil D, Barsyte-Lovejoy D, Li F, Poda G, Schapira M, Wu H, Dong A, Senisterra G, Stukalov A, Huber KV, Schönegger A, Marcellus R, Bilban M, Bock C, Brown PJ, Zuber J, Bennett KL, Al-Awar R, Delwel R, Nerlov C, Arrowsmith CH, Superti-Furga G. Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia. Nat Chem Biol. 2015 Aug;11(8):571-8. doi: 10.1038/nchembio.1859. Epub 2015 Jul 13. Erratum in: Nat Chem Biol. 2015 Oct;11(10):815. PubMed PMID: 26167872; PubMed Central PMCID: PMC4511833.