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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 h 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 PMC6704105
A549 10 μM 1 h 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 PMC6704105
MCF7 10 μM 1 h 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 PMC6704105
293FT 10 μM 1 h 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 PMC6704105
HepG2 10 μM and 20 μM 18 hours Inhibit H3K4me3 methylation and reverse statin-induced upregulation of PCSK9 PMC11699316
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. PMC11199983
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. PMC11199983
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. PMC10788880
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. PMC10788880
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. PMC4511833
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 PMC8215817
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 PMC8215817
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 PMC8215817
HCT116 10 µM 48 hours Repressed the expression of CBX8, CBX4 and CBX2, and decreased H3K4me3 level on m3eCBX8 PMC10680327
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. PMC7978315
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. PMC7978315
WPMY-1 0, 12.5, 25, 50, 100, 200, 400 μM 48 hours OICR-9429 was less cytotoxic to normal prostate cells WPMY-1. PMC7978315
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. PMC4511833
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. PMC10043273

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
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 PMC8215817
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 PMC6704105
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. PMC11199983
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 PMC10680327
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. PMC7978315
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. PMC10788880

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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