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Chemical Structure| 1801787-56-3 Chemical Structure| 1801787-56-3

Structure of OICR-9429
CAS No.: 1801787-56-3

Chemical Structure| 1801787-56-3

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OICR-9429 is an antagonist of the interaction of WDR5 with peptide regions of MLL and Histone 3.

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Product Details of OICR-9429

CAS No. :1801787-56-3
Formula : C29H32F3N5O3
M.W : 555.59
SMILES Code : O=C(C(C(C(F)(F)F)=C1)=CNC1=O)NC2=CC(C3=CC=CC(CN4CCOCC4)=C3)=CC=C2N5CCN(C)CC5
MDL No. :MFCD28411621
InChI Key :DJOVLOYCGXNVPI-UHFFFAOYSA-N
Pubchem ID :91623360

Safety of OICR-9429

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315
Precautionary Statements:P280

Related Pathways of OICR-9429

epigenetics

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
OVCAR3 10 µM 1 hour Study the effect of OICR-9429 on OVCAR3 cells, results showed that OICR-9429 inhibited the restoration of GSH metabolism, leading to a lethal increase in ROS levels Nat Commun. 2019 Aug 21;10(1):3761.
A549 10 µM 1 hour Study the effect of OICR-9429 on A549 cells, results showed that OICR-9429 inhibited the restoration of GSH metabolism, leading to a lethal increase in ROS levels Nat Commun. 2019 Aug 21;10(1):3761.
MCF7 10 µM 1 hour Study the effect of OICR-9429 on MCF7 cells, results showed that OICR-9429 inhibited the restoration of GSH metabolism, leading to a lethal increase in ROS levels Nat Commun. 2019 Aug 21;10(1):3761.
293FT 10 µM 1 hour Study the effect of OICR-9429 on 293FT cells, results showed that OICR-9429 inhibited the restoration of GSH metabolism, leading to a lethal increase in ROS levels Nat Commun. 2019 Aug 21;10(1):3761.
HepG2 10 µM and 20 µM 18 hours Inhibit H3K4me3 methylation and reverse statin-induced upregulation of PCSK9 J Lipid Res. 2025 Jan;66(1):100699.
THP-1 cells 20 µM 24 hours OICR-9429 significantly reduced the IC-induced secretion of IL-6, IL-8, TNF-α, and TF, indicating that it alleviates the pathological process of APS by downregulating FOXJ2 expression. Adv Sci (Weinh). 2024 Jun;11(24):e2309140.
Monocytes 20 µM 24 hours OICR-9429 significantly reduced the IC-induced secretion of IL-6, IL-8, TNF-α, and TF, indicating that it alleviates the pathological process of APS by downregulating FOXJ2 expression. Adv Sci (Weinh). 2024 Jun;11(24):e2309140.
THP-1 cells 20 µM 24 hours OICR-9429 treatment mitigated pyroptosis and apoptosis induced by β2GPI/anti-β2GPI complex in THP-1 cells and suppressed related inflammation. Clin Transl Med. 2024 Jan;14(1):e1539.
Primary monocytes 20 µM 24 hours OICR-9429 treatment mitigated pyroptosis and apoptosis induced by β2GPI/anti-β2GPI complex in primary monocytes and suppressed related inflammation. Clin Transl Med. 2024 Jan;14(1):e1539.
Human AML cells 5 µM 3 days To test the effect of OICR-9429 on human AML cells with N-terminal CEBPA mutations, results showed that OICR-9429 significantly reduced the viability of these cells. Nat Chem Biol. 2015 Aug;11(8):571-578.
T24 bladder cancer cells 70 µM 48 hours To evaluate the effect of OICR-9429 on bladder cancer cell viability, results showed that OICR-9429 significantly reduced cell viability J Exp Clin Cancer Res. 2021 Jun 21;40(1):203.
UM-UC-3 bladder cancer cells 70 µM 48 hours To evaluate the effect of OICR-9429 on bladder cancer cell viability, results showed that OICR-9429 significantly reduced cell viability J Exp Clin Cancer Res. 2021 Jun 21;40(1):203.
TCCSUP bladder cancer cells 120 µM 48 hours To evaluate the effect of OICR-9429 on bladder cancer cell viability, results showed that OICR-9429 significantly reduced cell viability J Exp Clin Cancer Res. 2021 Jun 21;40(1):203.
HCT116 10 µM 48 hours Repressed the expression of CBX8, CBX4 and CBX2, and decreased H3K4me3 level on m3eCBX8 Genome Biol. 2023 Nov 27;24(1):268.
DU145 0, 12.5, 25, 50, 100, 200, 400 µM 48 hours OICR-9429 significantly reduced the viability of PCa cells in a dose-dependent manner. Theranostics. 2021 Mar 4;11(10):4809-4824.
PC-3 0, 12.5, 25, 50, 100, 200, 400 µM 48 hours OICR-9429 significantly reduced the viability of PCa cells in a dose-dependent manner. Theranostics. 2021 Mar 4;11(10):4809-4824.
WPMY-1 0, 12.5, 25, 50, 100, 200, 400 µM 48 hours OICR-9429 was less cytotoxic to normal prostate cells WPMY-1. Theranostics. 2021 Mar 4;11(10):4809-4824.
Cebpap30/p30 cells 20 µM 6 days To test the effect of OICR-9429 on Cebpap30/p30 cells, results showed that OICR-9429 induced the expression of surface markers Mac-1 and Gr-1 and promoted myeloid differentiation. Nat Chem Biol. 2015 Aug;11(8):571-578.
LAN5 cells 20 µM 72 hours RNA-seq analysis was performed to compare the differences in molecular action mechanisms between OICR-9429 and the WBM site inhibitor in neuroblastoma cells. The results showed that OICR-9429 had a weak inhibitory effect on the proliferation of LAN5 cells and minimal impact on the p53 signaling pathway. Acta Pharmacol Sin. 2023 Apr;44(4):877-887.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice Prostate cancer xenograft model Subcutaneous injection 10 mg/kg Every 3 days for 4 weeks OICR-9429 significantly increased the sensitivity of PCa to cisplatin chemotherapy, as indicated by the decreased tumor volume and weight. Theranostics. 2021 Mar 4;11(10):4809-4824.
Mice Ovarian cancer PDX model Intraperitoneal injection 3 mg/kg Three times per week for up to 6 weeks Study the effect of OICR-9429 on ovarian cancer PDX model, results showed that OICR-9429 significantly enhanced the sensitivity of Topotecan chemotherapy, leading to decreased tumor volume and mass, reduced GSH concentration, increased ROS levels, and increased apoptotic cells Nat Commun. 2019 Aug 21;10(1):3761.
BALB/c mice Vascular APS model Intraperitoneal injection 5 mg/kg Once daily for 7 days OICR-9429 significantly reduced inflammation and thrombosis, alleviating the pathological process of APS by inhibiting the FOXJ2/SLAMF8/TREM1 signaling pathway. Adv Sci (Weinh). 2024 Jun;11(24):e2309140.
C57BL/6 J mice AOM/DSS-induced CRC model Intraperitoneal injection 5 mg/kg Three times per week, until the 10th week Repressed the size and number of AOM/DSS-induced tumors, and enhanced anti-tumor immunity Genome Biol. 2023 Nov 27;24(1):268.
BALB/c mice APS mouse model Intraperitoneal injection 5 mg/kg Once daily for 7 consecutive days OICR-9429 treatment mitigated inflammation and thrombosis in the APS mouse model and suppressed related pyroptosis and apoptosis. Clin Transl Med. 2024 Jan;14(1):e1539.
BALB/c Nude mice Bladder cancer xenograft model Intraperitoneal injection 60 mg/kg Every 2 days for 16 days To evaluate the effect of OICR-9429 on bladder cancer tumor growth, results showed that OICR-9429 significantly suppressed tumor growth and enhanced the efficacy of cisplatin J Exp Clin Cancer Res. 2021 Jun 21;40(1):203.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.80mL

0.36mL

0.18mL

9.00mL

1.80mL

0.90mL

18.00mL

3.60mL

1.80mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

[1]Getlik M, Smil D, et al. 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.

[2]Grebien F, Vedadi M, et al. Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia. Nat Chem Biol. 2015 Aug;11(8):571-578.

[3]Shimoda H, Doi S, et al. 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.

[4]Cao L, Wu G, et al. Genotoxic stress-triggered β-catenin/JDP2/PRMT5 complex facilitates reestablishing glutathione homeostasis. Nat Commun. 2019 Aug 21;10(1):3761.

[5]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.

[6]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. PMID: 26958703.

 

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