OICR-9429

SKU: orb1225889

Description

A potent, selective, small-molecule antagonist of WDR5-MLL interaction that binds to WDR5 with Kd of 93±28 nM; competitively disrupts the interaction with a high-affinity Wdr5-INteracting (WIN) peptide of MLL (Kdisp=64 nM), shows no significant binding or inhibition for 22 human methyltransferases, 9 different WD40- and histone reader domains; selectively inhibits proliferation and induces differentiation in p30-expressing human AML cells.

Key Properties

• CAS Number: 1801787-56-3
• MW: 555.5913
• Purity: >98% (HPLC)
• Formula: C₂₉H₃₂F₃N₅O₃
• SMILES: O=C(C(C(C(F)(F)F)=C1)=CNC1=O)NC2=CC(C3=CC=CC(CN4CCOCC4)=C3)=CC=C2N5CCN(C)CC5
• Target: HMTase
• Solubility: DMSO: ≥ 32 mg/mL

Bioactivity

• In Vivo:
  Animal model: xenograft mouse model. Dosage: 30 mg/kg, 60 mg/kg. Administration: 30 mg/kg, 60 mg/kg, i.p. Result: Suppressed tumour growth, small tumours and enhanced tumour sensitivity.
• In Vitro:
  Cell Proliferation Assay Cell line: BCa cell lines (T24, UM-UC-3 and TCCSUP). Concentration: 70 μM, 120 μM, 140 μM and 240 μM. Incubation time: 5 days. Result: Had a low proliferation rate and remarkably reduced the number of colonies formed by the three BCa cell lines in a dose-dependent manner. Cell Cytotoxicity Assay Cell line: BCa cell lines (T24, UM-UC-3 and TCCSUP). Concentration: 0-10 μM. Incubation time: 48 h. Result: Inhibited cell viability in a dose-dependent manner in BCa cell lines. Apoptosis Analysis Cell line: BCa cell lines (T24, UM-UC-3 and TCCSUP). Concentration: 70 μM, 120 μM, 140 μM and 240 μM. Incubation time: 24 h. Result: Showed no obvious apoptotic cells for 24 h but the apoptotic rate was significantly increased at 72 h and upregulated caspase 3/7 activity. Cell Migration Assay Cell line: BCa cell lines (T24, UM-UC-3 and TCCSUP). Concentration: 70 μM, 120 μM, 140 μM and 240 μM. Incubation time: 24 h, 48 h. Result: Reduced the migratory speed and decreased the migration of the three BCa cell lines. Cell Invasion Assay Cell line: BCa cell lines (T24, UM-UC-3 and TCCSUP). Concentration: 70 μM, 120 μM, 140 μM and 240 μM. Incubation time: 24 h, 48 h. Result: Decreased the invasion of the three BCa cell lines. Western blot analysis. Cell line: BCa cell lines (T24, UM-UC-3 and TCCSUP). Concentration: 70 μM, 120 μM, 140 μM and 240 μM. Incubation time: 48 h. Result: Showed significant downregulation of H3K4me3 in treated cells but not WDR5 or total H3.Reduced the expression of PD-L1 induced by IFN-γ in a dose-dependent manner at both the RNA and protein levels. RT-PCR Cell line: BCa cell lines (T24, UM-UC-3 and TCCSUP). Concentration: 70 μM, 120 μM, 140 μM and 240 μM. Incubation time: 48 h. Result: Downregulated some genes related to the cell cycle, such as CDK1, PLK1, CCNE2, CCNB1, CCNA2, AURKA, and E2F1, genes related to apoptosis and DNA repair, such as BIRC5, XRCC2, AURKA, E2F1, and MCM2, and genes related to metastasis, such as AURKA and FOXM1.Cell Cycle Analysis Cell line: BCa cell lines (T24, UM-UC-3 and TCCSUP). Concentration: 70 μM, 120 μM, 140 μM and 240 μM. Incubation time: 48 h. Result: Increased the cell population in the G0/G1 phase of three BCa cells and reduced cell population in the S and G2/M phases.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

OICR9429 | OICR 9429

Quick Database Links

Gene Symbol

HMTase