BAY1217389

SKU: orb1222645

Description

BAY1217389 is an orally bioavailable, selective inhibitor of the serine/threonine kinase monopolar spindle 1 (Mps1, TTK), with potential antineoplastic activity. Upon administration, the Mps1 inhibitor BAY 1217389 selectively binds to and inhibits the activity of Mps1. This inactivates the spindle assembly checkpoint (SAC), accelerates mitosis, causes chromosomal misalignment and missegregation, and mitotic checkpoint complex destabilization. This induces cell death in Mps1-overexpressing cancer cells.

Key Properties

• CAS Number: 1554458-53-5
• MW: 561.5
• Purity: >98% (HPLC)
• Formula: C₂₇H₂₄F₅N₅O₃
• SMILES: Cc1c(ccc(c1)c1cnc2n1nc(cc2NCCC(F)(F)F)Oc1c(c(c(cc1)OC)F)F)C(=O)NC1CC1
• Target: Mps1
• Solubility: DMSO : ≥ 28 mg/mL; 49.87 mM

Bioactivity

• In Vivo:
  BAY 1217389 achieves moderate efficacy in monotherapy in tumor xenograft studies. However, in line with its unique mode of action, when combines with paclitaxel, low doses of Mps1 inhibitor reduces paclitaxel-induced mitotic arrest in line with weakening of SAC activity. As a result, combination therapy strongly improves efficacy over paclitaxel or Mps1 inhibitor monotreatment at the respective MTDs in a broad range of xenograft models including those showing acquired or intrinsic paclitaxel-resistance. BAY 1217389 shows good tolerability without adding toxicity to paclitaxel monotherapy.
• In Vitro:
  BAY 1217389 inhibits Mps1 kinase activity with IC50 value below 10 nM while showing an excellent selectivity profile. In cellular mechanistic assays BAY 1217389 abrogates nocodazole-induced SAC activity and induces premature exit from mitosis resulting in multinuclearity and tumor cell death. BAY 1217389 efficiently inhibits tumor cell proliferation in vitro.

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

BAY1217389 | BAY-1217389 | BAY 1217389

Quick Database Links

Gene Symbol

Mps1