Cell lines

Human melanoma A375 and Hs 294T cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

24 h, 10-100 nM

Applications

BI6727 (Volasertib) is a second generation small molecule Plk1 inhibitor and has been reported to be a promising agent for treatment of several cancers. BI6727 (Volasertib) inhibits growth, viability and induces apoptosis of melanoma cells.

Animal models

Patients aged ≥ 18 years with locally advanced or metastatic urothelial cancer

Dosage form

BI6727 (Volasertib) was administered by 2-hour intravenous infusion at a dose of 300 mg once daily on day 1 of 3-week treatment cycles.

Application

BI6727 (Volasertib) has an acceptable safety profile as a second-line treatment for advanced or metastatic urothelial cancer, but only modest antitumor activity for further evaluation as a monotherapy.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

BI6727 (Volasertib) is a selective inhibitor of Plk1, Plk2, and Plk3 with IC50 value of 0.87, 5 and 56 nM/L, respectively [1].

Polo-like kinase 1 (Plk1) is an early trigger for G2/M phase transition and is over-expressed in a variety of cancers for that being regarded as a promising target for cancer treatment [1].

BI6727 (Volasertib) is a potent Plk1 inhibitor and is regarded as a promising drug for multiple cancers in clinic. When tested with NB TICs and normal human pediatric SKPs (neural crest-like stem cells), BI6727 (Volasertib) treatment inhibits NB TICs with EC50 value of 21 nM/L and 2.8 μM/L on SKPs and decresed TIC survival [2]. It has been reported that BI6727 (Volasertib) inhibited proliferation of multiple cell lines, including HCT 116(caicinomas of the colon), NCI-H460 (lung cancer), BRO (melanoma), GRANTA (hematopoitic cancers) with EC50 value of 23 nmol/l, 21 nmol/l, 11 nmol/l, 15 nmol/l, respectively [1] [3].

In nude mice model with HCT 16 cells (colon carcinoma) subcutaneous xenograft, oral administration of BI6727 (Volasertib) delays tumor growth, decreased tumor size and induced tumor regression by increasing the mitotic index and apoptosis. And the same results were achieved when tested with NCI-H4660 (non-small cell lung carcinoma), xenograft model [1].

References:
[1].  Rudolph, D., et al., BI 6727, a Polo-like kinase inhibitor with improved pharmacokinetic profile and broad antitumor activity. Clin Cancer Res, 2009. 15(9): p. 3094-102.
[2].  Grinshtein, N., et al., Small molecule kinase inhibitor screen identifies polo-like kinase 1 as a target for neuroblastoma tumor-initiating cells. Cancer Res, 2011. 71(4): p. 1385-95.
[3].   Munch, C., et al., Therapeutic polo-like kinase 1 inhibition results in mitotic arrest and subsequent cell death of blasts in the bone marrow of AML patients and has similar effects in non-neoplastic cell lines. Leuk Res, 2015. 39(4): p. 462-70.