AZ3146

SKU: orb1305161

Description

AZ3146 is a potent and selective small molecule inhibitor of the Mps1 kinase, demonstrating an IC50 of approximately 35 nM. It is widely used in biochemical and cellular research to study mitotic checkpoint signaling and has been employed in both in vitro assays and in vivo xenograft models to investigate its potential in oncology.

Research Area

Signal Transduction

Key Properties

• CAS Number: 1124329-14-1
• MW: 452.55
• Purity: 98.03%
• Formula: C₂₄H₃₂N₆O₃
• SMILES: O=C1N(C=2C(N1C)=CN=C(NC3=C(OC)C=C(OC4CCN(C)CC4)C=C3)N2)C5CCCC5
• Target: Kinesin
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.42 mM);DMSO:11.3 mg/mL (24.97 mM);Ethanol:33.9 mg/mL (74.91 mM)

Bioactivity

• Target IC50:
  Mps1:35 nM
• In Vivo:
  AZ3146 does not affect the mitosis-specific phosphorylated forms of Aurora B and BubR1. When HeLa cells were treated with nocodazole and 2 μM AZ3146, mitosis was briefly delayed before cells resumed genome replication, indicating that AZ3146 can override the Spindle Assembly Checkpoint (SAC). Notably, 90% of AZ3146-treated HeLa cells exhibited abnormal mitosis, with ~50% of cells entering late mitosis failing to correct their chromosomes and ~30% completing mitosis without apparent chromosome segregation. AZ3146 also inhibits FAK, JNK1, JNK2, and Kit, and significantly reduces Mps1 phosphorylation in cells. Furthermore, AZ3146 inhibits established SAC signaling, as evident from the facilitated conclusion of mitosis after release from nocodazole block, and significantly impacts the kinetochore localization of Mad2, reducing it to ~15%, but does not significantly affect Mad1, which remains at ~60%. Before mitosis, Mps1 inhibition by AZ3146 blocks the accumulation of Mad1 and Mad2 at the kinetochore. However, if Mps1 is inhibited by AZ3146 after entering mitosis, the Mad1-C-Mad2 core complex still binds to the kinetochore, but O-Mad2 cannot accumulate at the core. In other undisturbed mitoses, AZ3146 reduces the time to complete mitosis from 90 minutes in the control group to 32 minutes.
• Cell Research:
  AZ3146 is disolved in DMSO (100 mM) and diluted into 100 μM, 10 μM, 1 μM and 0.1 μM sequentially with DMEM containing 10% FBS before use. The TTK inhibitor AZ3146 is disolved in DMSO at a concentration in 100 mM and diluted into 100 μM, 10 μM, 1 μM and 0.1 μM sequentially with DMEM containing 10% FBS before use. In vitrocytotoxicity assays are performed. HCC cells are plated into 96-well plates at the density of 3×103 per well. AZ3146 is added in the indicated concentrations the next day. The inhibitor treated cells are cultured and tested at a 24-hour intervals for 3-4 days using CCK-8.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

AZ 3146, AZ3146, AZ-3146, inhibit, Mps1, Inhibitor, Monopolar spindle 1

Compound Identifiers

PubChem CID

56973724