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Details

Stereochemistry ACHIRAL
Molecular Formula C16H21Cl2N3O2
Molecular Weight 358.263
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BENDAMUSTINE

SMILES

CN1C(CCCC(O)=O)=NC2=C1C=CC(=C2)N(CCCl)CCCl

InChI

InChIKey=YTKUWDBFDASYHO-UHFFFAOYSA-N
InChI=1S/C16H21Cl2N3O2/c1-20-14-6-5-12(21(9-7-17)10-8-18)11-13(14)19-15(20)3-2-4-16(22)23/h5-6,11H,2-4,7-10H2,1H3,(H,22,23)

HIDE SMILES / InChI
Bendamustine, brand name Treanda, is a chemotherapeutic agent that displays a unique pattern of cytotoxicity compared with conventional alkylating agents. Treanda is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL), in addition Trenda in phase III of clinical trial for the treatment patients with indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. Bendamustine is a bifunctional mechlorethamine derivative. Mechlorethamine and its derivatives dissociate into electrophilic alkyl groups. These groups form covalent bonds with electron-rich nucleophilic moieties. The bifunctional covalent linkage can lead to cell death via several pathways. The exact mechanism of action of bendamustine remains unknown. Molecular analyses have revealed that bendamustine differs from other alkylating agents in its mechanism of action. Differences have been observed about its effects on DNA repair and cell cycle progression. Moreover, bendamustine can induce cell death through both apoptotic and nonapoptotic pathways, thereby retaining activity even in cells without a functional apoptotic pathway. Bendamustine possesses the typical adverse reactions for the nitrogen mustards, and include nausea, fatigue, vomiting, diarrhea, fever, constipation, loss of appetite, cough, headache, unintentional weight loss.

CNS Activity

Curator's Comment: Known to be CNS penetrant in murine. Human data not available

Originator

Curator's Comment: Bendamustine was first synthesized in 1963 in the former Germany Democratic Republic by Ozegowski and Krebs. And re-discovered in 1990s with multiple successive well-designed studies.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: CHEMBL2311221
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
TREANDA

Approved Use

TREANDA® (bendamustine hydrochloride) for Injection is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL). Efficacy relative to first line therapies other than chlorambucil has not been established.

Launch Date

1.20597119E12
Primary
Treanda

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5.32 μg/mL
120 mg/m² single, intravenous
dose: 120 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
BENDAMUSTINE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
8797 ng/mL
160 mg/kg single, intravenous
dose: 160 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
BENDAMUSTINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
6398 ng × h/mL
120 mg/m² single, intravenous
dose: 120 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
BENDAMUSTINE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
444631 ng × min/mL
160 mg/kg single, intravenous
dose: 160 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
BENDAMUSTINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
11.17 μg × h/mL
4.2 mg/kg single, intravenous
dose: 4.2 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
BENDAMUSTINE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
0.65 h
120 mg/m² single, intravenous
dose: 120 mg/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
BENDAMUSTINE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
41 min
160 mg/kg single, intravenous
dose: 160 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
BENDAMUSTINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
36.1 min
4.2 mg/kg single, intravenous
dose: 4.2 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
BENDAMUSTINE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
5%
BENDAMUSTINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
100 mg/m2 2 times / 4 weeks steady, intravenous
Recommended
Dose: 100 mg/m2, 2 times / 4 weeks
Route: intravenous
Route: steady
Dose: 100 mg/m2, 2 times / 4 weeks
Sources:
unhealthy, 45-77 years
n = 153
Health Status: unhealthy
Condition: Chronic Lymphocytic Leukemia
Age Group: 45-77 years
Sex: M+F
Population Size: 153
Sources:
Disc. AE: Hypersensitivity, Pyrexia...
AEs leading to
discontinuation/dose reduction:
Hypersensitivity (2%)
Pyrexia (1%)
Sources:
150 mg/m2 2 times / 4 weeks steady, intravenous
Dose: 150 mg/m2, 2 times / 4 weeks
Route: intravenous
Route: steady
Dose: 150 mg/m2, 2 times / 4 weeks
Sources:
unhealthy, 48 years
n = 1
Health Status: unhealthy
Condition: advanced progressive breast cancer
Age Group: 48 years
Sex: F
Population Size: 1
Sources:
Other AEs: Pneumocystis carinii pneumonia...
Other AEs:
Pneumocystis carinii pneumonia (grade 5, 1 patient)
Sources:
280 mg/m2 single, intravenous
Highest studied dose
Dose: 280 mg/m2
Route: intravenous
Route: single
Dose: 280 mg/m2
Sources:
unhealthy, adult
n = 4
Health Status: unhealthy
Age Group: adult
Population Size: 4
Sources:
DLT: QT interval prolonged, Sinus tachycardia...
Dose limiting toxicities:
QT interval prolonged (1 patient)
Sinus tachycardia (1 patient)
ECG Nonspecific ST-T change (2 patients)
Left anterior fascicular block (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Pyrexia 1%
Disc. AE
100 mg/m2 2 times / 4 weeks steady, intravenous
Recommended
Dose: 100 mg/m2, 2 times / 4 weeks
Route: intravenous
Route: steady
Dose: 100 mg/m2, 2 times / 4 weeks
Sources:
unhealthy, 45-77 years
n = 153
Health Status: unhealthy
Condition: Chronic Lymphocytic Leukemia
Age Group: 45-77 years
Sex: M+F
Population Size: 153
Sources:
Hypersensitivity 2%
Disc. AE
100 mg/m2 2 times / 4 weeks steady, intravenous
Recommended
Dose: 100 mg/m2, 2 times / 4 weeks
Route: intravenous
Route: steady
Dose: 100 mg/m2, 2 times / 4 weeks
Sources:
unhealthy, 45-77 years
n = 153
Health Status: unhealthy
Condition: Chronic Lymphocytic Leukemia
Age Group: 45-77 years
Sex: M+F
Population Size: 153
Sources:
Pneumocystis carinii pneumonia grade 5, 1 patient
150 mg/m2 2 times / 4 weeks steady, intravenous
Dose: 150 mg/m2, 2 times / 4 weeks
Route: intravenous
Route: steady
Dose: 150 mg/m2, 2 times / 4 weeks
Sources:
unhealthy, 48 years
n = 1
Health Status: unhealthy
Condition: advanced progressive breast cancer
Age Group: 48 years
Sex: F
Population Size: 1
Sources:
Left anterior fascicular block 1 patient
DLT
280 mg/m2 single, intravenous
Highest studied dose
Dose: 280 mg/m2
Route: intravenous
Route: single
Dose: 280 mg/m2
Sources:
unhealthy, adult
n = 4
Health Status: unhealthy
Age Group: adult
Population Size: 4
Sources:
QT interval prolonged 1 patient
DLT
280 mg/m2 single, intravenous
Highest studied dose
Dose: 280 mg/m2
Route: intravenous
Route: single
Dose: 280 mg/m2
Sources:
unhealthy, adult
n = 4
Health Status: unhealthy
Age Group: adult
Population Size: 4
Sources:
Sinus tachycardia 1 patient
DLT
280 mg/m2 single, intravenous
Highest studied dose
Dose: 280 mg/m2
Route: intravenous
Route: single
Dose: 280 mg/m2
Sources:
unhealthy, adult
n = 4
Health Status: unhealthy
Age Group: adult
Population Size: 4
Sources:
ECG Nonspecific ST-T change 2 patients
DLT
280 mg/m2 single, intravenous
Highest studied dose
Dose: 280 mg/m2
Route: intravenous
Route: single
Dose: 280 mg/m2
Sources:
unhealthy, adult
n = 4
Health Status: unhealthy
Age Group: adult
Population Size: 4
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
likely
likely
yes
likely (co-administration study)
Comment: Inhibitors of CYP1A2 (e.g., fluvoxamine, ciprofloxacin) have potential to increase plasma concentrations of bendamustine; Inducers of CYP1A2 (e.g., omeprazole, smoking) have potential to decrease plasma concentrations of bendamustine (see label: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022249lbl.pdf#page=3)
Page: 3.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Upon drug-induced apoptosis in lymphoma cells X-linked inhibitor of apoptosis (XIAP) translocates from the cytosol to the nucleus.
2004 Jul
Bendamustine HCL for the treatment of relapsed indolent non-Hodgkin's lymphoma.
2008 Aug
Bendamustine is effective in p53-deficient B-cell neoplasms and requires oxidative stress and caspase-independent signaling.
2008 Nov 1
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
2015 May 18
Patents

Sample Use Guides

TREANDA (bendamustine hydrochloride) is intended for administration as an intravenous infusion over 30 minutes. The recommended dose is 100 mg/m2 administered intravenously on Days 1 and 2 of a 28-day cycle, up to 6 cycles. Consider using allopurinol as prevention for patients at high risk of tumor lysis syndrome for the first few weeks of treatment.
Route of Administration: Intravenous
Using chronic lymphocytic leukemia (CLL) cells taken from 37 previously treated and untreated CLL patients, was investigated the influence of bendamustine alone, and in combination with fludarabine, on the induction of apoptosis and changes of Bcl-2 and Bax expression on mRNA and protein level. Using bendamustine alone in concentrations from 1 microg/ml to 50 microg/ml, a dose- and time-dependent manner of cytotoxicity from 30.4% to 94.8% after 48 h could be observed. The LD50 for untreated and pretreated CLL cells was 7.3 or 4.4 microg/ml, respectively. The level of the initial Bcl-2 and Bax protein and the m-RNA expression remained unchanged during the incubation with bendamustine.
Name Type Language
BENDAMUSTINE
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
1H-BENZIMIDAZOLE-2-BUTANOIC ACID, 5-(BIS(2-CHLOROETHYL)AMINO)-1-METHYL-
Common Name English
BENDAMUSTINE [VANDF]
Common Name English
BENDAMUSTINE [MI]
Common Name English
BENDAMUSTINE [HSDB]
Common Name English
Bendamustine [WHO-DD]
Common Name English
4-(5-(BIS(2-CHLOROETHYL)AMINO)-1-METHYL-1H-BENZIMIDAZOLE-2-YL)BUTANOIC ACID
Systematic Name English
bendamustine [INN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 584417
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
WHO-ATC L01AA09
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
LIVERTOX NBK548108
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
NDF-RT N0000000236
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
FDA ORPHAN DRUG 431814
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
FDA ORPHAN DRUG 486215
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
NCI_THESAURUS C697
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
NDF-RT N0000175558
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
FDA ORPHAN DRUG 430314
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
WHO-VATC QL01AA09
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
Code System Code Type Description
FDA UNII
9266D9P3PQ
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
PRIMARY
ChEMBL
CHEMBL487253
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
PRIMARY
PUBCHEM
65628
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
PRIMARY
EPA CompTox
DTXSID2046888
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
PRIMARY
HSDB
7763
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
PRIMARY
IUPHAR
7478
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
PRIMARY
INN
5228
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
PRIMARY
MESH
C001758
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
PRIMARY
SMS_ID
300000047632
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
PRIMARY
EVMPD
SUB05707MIG
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
PRIMARY
DAILYMED
9266D9P3PQ
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
PRIMARY
MERCK INDEX
m2306
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
PRIMARY Merck Index
DRUG CENTRAL
302
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
PRIMARY
NCI_THESAURUS
C73261
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
PRIMARY
DRUG BANK
DB06769
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
PRIMARY
WIKIPEDIA
BENDAMUSTINE
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
PRIMARY
LACTMED
Bendamustine
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
PRIMARY
RXCUI
134547
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
PRIMARY RxNorm
CAS
16506-27-7
Created by admin on Fri Dec 15 16:01:02 UTC 2023 , Edited by admin on Fri Dec 15 16:01:02 UTC 2023
PRIMARY