Volasertib

SKU: orb1224065

Description

Volasertib (BI 6727) is a potent, selective Polo-like kinase (PLK) inhibitor with IC50 of 0.87, 5 and 56 nM for PLK1, 2 and 3, respectively; displays no inhibitory activity against a panel of >50 other kinases; inhibits proliferation of multiple cell lines derived from various cancer tissues, including HCT116 (EC50=23 nM) and NCI-H460 (EC50=21 nM),BRO (EC50=11 nM), and hematopoietic cancer cell HL-60 (EC50=32 nM); demonstrates marked antitumor activity in multiple cancer models, including a model of taxane-resistant colorectal cancer.Blood Cancer Phase 3 Clinical.

Key Properties

• CAS Number: 755038-65-4
• MW: 618.8126
• Purity: >98% (HPLC)
• Formula: C₃₄H₅₀N₈O₃
• SMILES: O=C(N[C@H]1CC[C@@H](N2CCN(CC3CC3)CC2)CC1)C4=CC=C(NC(N=C5N(C(C)C)[C@@H]6CC)=NC=C5N(C)C6=O)C(OC)=C4
• Target: PLK
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  Animal model: Female BomTac: NMRI-Foxn1nu mice (Taconic) were grafted s. c. with HCT 116 human colon carcinoma cells (ATCC CCL-247). Dosage: A total weekly dose of 50 mg/kg. Administration: Oral; once a week, twice a week, or daily; for 40 days. Result: Showed comparable efficacy and were well tolerated. Animal model: Female BomTac: NMRI-Foxn1nu mice and male Wistar rats of the strain Crl: WI. Dosage: 35 mg/kg (mice) or 10 mg/kg (rat) (Pharmacokinetic Analysis). Administration: IV 5-minute infusion; a single dose 5-minute infusion. Result: Had high volume of distribution and a long terminal half-life in mice (Vss = 7.6 L/kg, t1/2 = 46 h) and rats (Vss = 22 L/kg, t1/2 = 54 h).
• In Vitro:
  Cell Proliferation Assay Cell line: Multiple cell lines. Concentration: 0.01-10000 nM Incubation time: 72 hours. Result: Inhibited proliferation of multiple cell lines derived from various cancer tissues, including carcinomas of the colon (HCT 116, EC50 = 23 nmol/L) and lung (NCI-H460, EC50 = 21 nmol/L), melanoma (BRO, EC50 = 11 nmol/L), and hematopoietic cancers (GRANTA-519, EC50 = 15 nmol/L; HL-60, EC50 = 32 nmol/L; THP-1, E50=36 nmol/L and Raji, EC50 = 37 nmol/L) with EC50 values of 11 to 37 nmol/L. Apoptosis Analysis Cell line: NCI-H460 cells. Concentration: 100 nM. Incubation time: 24, 48, 72 hours. Result: G2-M arrest at 24 hours was followed by induction of apoptosis at 48 hours. Cell Cycle Analysis Cell line: NCI-H460 cells. Concentration: 10, 30, 100, 300, 1000 nM. Incubation time: 24 hours. Result: Resulted in accumulation of cells with 4N DNA content, indicative of a cell cycle block in G2-M phase.

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

BI 6727 | BI-6727 | BI6727

Quick Database Links

Gene Symbol

PLK