product name Bendamustine HCl
Description: Bendamustine HCl (also called SDX-105/Cytostasane HCl) is a DNA-damaging agent with IC50 of 50 μM in cell-free assay. It has been reported that bendamustine is activated under DNA damage stress and apoptosis. Bendamustine inhibits mitotic checkpoints and induces mitotic catastrophe by inhibiting several mitosis-related genes such as Polo-like kinase 1, Aurora kinase A, and Cyclin B1. In myeloma cell lines, bendamustine induced apoptosis by cleavage of caspase 3, and resulted in G2 cell cycle arrest.
References: Clin Cancer Res. 2008 Jan 1;14(1):309-17; Br J Pharmacol. 2012 Oct;167(4):881-91.
394.72
Formula
C16H21Cl2N3O2.HCl
CAS No.
3543-75-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 78 mg/mL (197.6 mM)
Water: 2 mg/mL (5.0 mM)
Ethanol: 17 mg/mL (43.1 mM)
Solubility (In vivo)
1% DMSO+30% polyethylene glycol+1% Tween 80: 30 mg/mL
Synonyms
SDX-105 (Cytostasane) HCl
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19413392
| In Vitro |
In vitro activity: DNA single- and double-strand breaks caused by Bendamustine are more extensive and significantly more durable than those caused by cyclophosphamide, cisplatinum, or carmustine. Bendamustine specifically regulates, transcriptionally and posttranslationally, genes involved in apoptosis, DNA repair, and mitotic checkpoints. Bendamustine uniquely regulates DNA repair pathways in non–Hodgkins lymphoma cells compared with other alkylators. Bendamustine inhibits mitotic checkpoints and induces mitotic catastrophe. Treatment with Bendamustine results in a 60% to 80% down-regulation of the mRNA expression of all three of these genes [polo-like kinase 1 (PLK-1), Aurora Kinase A, and cyclin B1] in SU-DHL-9 cells. Twenty-six percent of the Bendamustine-treated MCF-7/ADR cells showed micronucleation compared with only 6% in DMSO control cells. Using Bendamustine alone in concentrations from 1 μg/mL to 50 μg/mL, a dose- and time-dependent manner of cytotoxicity from 30.4% to 94.8% after 48 hours could be observed. The LD50 for untreated and pretreated CLL cells is 7.3 or 4.4 μg /mL, respectively. Myeloid and breast carcinoma cell lines are resistant towards Bendamustine with the exception of HL-60 cells which exhibit an intermediate sensitivity. Bendamustine is found to have a very low clastogenic effect as compared with equimolar doses of lomustine. Kinase Assay: Cell Assay: SU-DHL-1 and SU-DHL-9 cells are preincubated for 30 minutes with either 6 mM methoxyamine or 50 μM O6-benzylguanine, inhibitors of Ape-1 base excision repair enzyme, or alkylguanyl transferase enzyme, respectively. The cells are then exposed to various concentrations of Bendamustine for 72 hours. Cytotoxicity is evaluated by the MTT viability assay and an IC50 is determined as the drug concentration that inhibited by 50% the viability value of the untreated control. Analyses are done. |
|---|---|
| In Vivo | A single dose of Bendamustine at 25 mg/kg demonstrates significant activity in all three tumor lines (DoHH-2, Granta 519 and RAMOS). DoHH-2 is the most sensitive, with 30% ORR and a 69% inhibition in tumor growth. Growth of Granta 519 and RAMOS is also inhibited by Bendamustine (%TGI of 74% and 81%, respectively), and the effect is more durable in Granta 519 (%TGD of 124%) than for DoHH-2 or RAMOS (69% and 43%, respectively). |
| Animal model | C.B.-17 scid mice bearing DoHH-2, Granta 519 or C.B.-17 scid-bg mice bearing SuDHL-4, RAMOS |
| Formulation & Dosage | 25 mg/kg; i.v. injection |
| References | Clin Cancer Res. 2008 Jan 1;14(1):309-17; Br J Pharmacol. 2012 Oct;167(4):881-91. |
