Bendamustine hydrochloride

Description

Bendamustine hydrochloride is a purine analog and DNA alkylating agent. It inhibits growth of SKW-3, Reh, CML-T1, BV-173, and HL-60 leukemia cell lines (IC50s = 27.0, 28.6, 15.6, 20.8, and 57.7 μM, respectively) but not MCF-7 and MDA-MB-231 breast cancer cell lines (IC50s = >200 and >200 μM, respectively). It kills B cell-chronic lymphocytic leukemia (B-CLL) cells derived from na?ve and bendamustine-pretreated patients (LD50s = 6.8-8.3 and 3.8-4.9 mg/ml, respectively).

Chemical properties

Pale Brown Crystals

The Uses of Bendamustine hydrochloride

Bendamustine hydrochloride is a DNA-damaging agent with IC50 of 50 μM. It is a nitrogen mustard purine analog alkylator. It Used as an anticancer drug.

brand name

Ribomustine (Amcis AG, Switzerland).

General Description

Bendamustine hydrochloride comprises 2-chloroethylamine alkylating group, a butyric acid side chain and a benzimidazole ring in its structure and is a nitrogen mustard. It is catabolized in the liver by the enzyme cytochrome P450 1A2 into γ hydroxyl-bendamustine and N-desmethyl-bendamustine.

Biological Activity

Cytostatic agent that displays activity in non-Hodgkin's lymphomas. Exhibits bifunctionality; combines DNA alkylating properties with those of purine analogs.

Biochem/physiol Actions

Bendamustine is a therapeutic agent employed in treating lymphomas and chronic lymphocytic leukemia. It may be useful in central nervous system (CNS) malignancies treatment regimen due to its penetration capacity into brain tissue. Bendamustine is a promising candidate for non-Hodgkin lymphoma and Hodgkin lymphoma therapies.

Clinical Use

Alkylating agent:

CLL, NHL and multiple myeloma

Drug interactions

Potentially hazardous interactions with other drugs
Antipsychotics: avoid with clozapine (increased risk of agranulocytosis).

Metabolism

A major route of clearance of bendamustine is the hydrolysis to monohydroxy- and dihydroxybendamustine. Formation of N-desmethyl-bendamustine and gamma-hydroxy-bendamustine by hepatic metabolism involves cytochrome P450 (CYP) 1A2 isoenzyme. Another major route of bendamustine metabolism involves conjugation with glutathione. Excreted in the urine and faeces as unchanged drug and metabolites.

storage

Desiccate at RT

References

[1]. leoni lm, bailey b, reifert j, bendall hh, zeller rw, corbeil j, elliott g, niemeyer cc. bendamustine (treanda) displays a distinct pattern of cytotoxicity and unique mechanistic features compared with other alkylating agents. clin cancer res. 2008 jan 1;14(1):309-17.
[2]. gaul l, mandl-weber s, baumann p, emmerich b, schmidmaier r. bendamustine induces g2 cell cycle arrest and apoptosis in myeloma cells: the role of atm-chk2-cdc25a and atm-p53-p21-pathways. j cancer res clin oncol. 2008 feb;134(2):245-53.
[3]. roué g, lópez-guerra m, milpied p, pérez-galán p, villamor n, montserrat e, campo e, colomer d. bendamustine is effective in p53-deficient b-cell neoplasms and requires oxidative stress and caspase-independent signaling. clin cancer res. 2008 nov 1;14(21):6907-15.
[4]. cai b, wang s, huang j, lee ck, gao c, liu b. cladribine and bendamustine exhibit inhibitory activity in dexamethasone-sensitive and -resistant multiple myeloma cells. am j transl res. 2013;5(1):36-46.