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| | Volasertib trihydrochloride Basic information |
| | Volasertib trihydrochloride Chemical Properties |
| | Volasertib trihydrochloride Usage And Synthesis |
| Uses | Volasertib (BI 6727) trihydrochloride is an orally active, highly potent and ATP-competitive Polo-like kinase 1 (PLK1) inhibitor with an IC50 of 0.87 nM. Volasertib trihydrochloride inhibits PLK2 and PLK3 with IC50s of 5 and 56 nM, respectively. Volasertib trihydrochloride induces mitotic arrest and apoptosis. Volasertib trihydrochloride, a dihydropteridinone derivative, shows marked antitumor activity in multiple cancer models[1][2]. | | in vivo | Volasertib trihydrochloride (BI 6727 trihydrochloride; A total weekly dose of 50 mg/kg; Oral; once a week, twice a week, or daily; for 40 days) shows comparable efficacy in human colon carcinoma xenograft models[1].
Volasertib trihydrochloride (15, 20, or 25 mg/kg/day; i.v.; 2 consecutive days per week; for 40 days) leads to significant tumor growth delay and even tumor regression in human colon carcinoma xenograft models [1].
Volasertib trihydrochloride (70 mg/kg given once weekly or 10 mg/kg daily; oral) significantly delays tumor growth in a non-small cell lung carcinoma xenograft model derived from NCI-H460 cells[1].
Volasertib (a single dose of 40 mg/kg; iv) causes a significant (13-fold) increase in mitotic cells in HCT 116 tumor-bearing nude mice[1].
Volasertib has 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)[1].
| Animal Model: | Female BomTac:NMRI-Foxn1nu mice (Taconic) were grafted s.c. with HCT 116 human colon carcinoma cells (ATCC CCL-247)[1] | | 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.
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| Animal Model: | Female BomTac:NMRI-Foxn1nu mice and male Wistar rats of the strain Crl:WI[1] | | 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).
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| | IC 50 | PLK1: 0.87 nM (IC50); PLK2: 5 nM (IC50); PLK3: 56 nM (IC50) | | References | [1] Xie FF, et al. Volasertib suppresses tumor growth in cervical cancer. Am J Cancer Res. 2015 Nov 15;5(12):3548-59. PMID:26885445
[2] Rudolph D, et al. BI 6727, a Polo-like kinase inhibitor with improved pharmacokinetic profile and broad antitumor activity.Clin Cancer Res. 2009 May 1;15(9):3094-102. Epub DOI:10.1158/1078-0432.CCR-08-2445 |
| | Volasertib trihydrochloride Preparation Products And Raw materials |
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