Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C16H21Cl2N3O2.ClH |
| Molecular Weight | 394.724 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.CN1C(CCCC(O)=O)=NC2=C1C=CC(=C2)N(CCCl)CCCl
InChI
InChIKey=ZHSKUOZOLHMKEA-UHFFFAOYSA-N
InChI=1S/C16H21Cl2N3O2.ClH/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);1H
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | C16H21Cl2N3O2 |
| Molecular Weight | 358.263 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26783429
Curator's Comment: Known to be CNS penetrant in murine. Human data not available
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21695099
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
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2311221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22362008 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | TREANDA Approved UseTREANDA® (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 Date2008 |
|||
| Primary | Treanda Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
8797 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/17486132 |
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 |
|
5.32 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23322528 |
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 |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
444631 ng × min/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/17486132 |
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 |
|
6398 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23322528 |
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 |
|
11.17 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/4095129 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
41 min EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/17486132 |
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 |
|
0.65 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23322528 |
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 |
|
36.1 min EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/4095129 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
5% |
BENDAMUSTINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse 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 Health Status: unhealthy Age Group: 45-77 years Sex: M+F Sources: |
Disc. AE: Hypersensitivity, Pyrexia... AEs leading to discontinuation/dose reduction: Hypersensitivity (2%) Sources: Pyrexia (1%) |
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 |
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 Health Status: unhealthy Age Group: adult Sources: |
DLT: QT interval prolonged, Sinus tachycardia... Dose limiting toxicities: QT interval prolonged (1 patient) Sources: Sinus tachycardia (1 patient) ECG Nonspecific ST-T change (2 patients) Left anterior fascicular block (1 patient) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| 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 Health Status: unhealthy Age Group: 45-77 years Sex: M+F 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 Health Status: unhealthy Age Group: 45-77 years Sex: M+F 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 |
| 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 Health Status: unhealthy Age Group: adult 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 Health Status: unhealthy Age Group: adult 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 Health Status: unhealthy Age Group: adult 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 Health Status: unhealthy Age Group: adult Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| no | ||||
Page: 3.0 |
unlikely | |||
Page: 3.0 |
unlikely | |||
Page: 3.0 |
unlikely | |||
Page: 3.0 |
unlikely | |||
Page: 3.0 |
unlikely | |||
| yes [IC50 0.8 uM] |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Page: 3.0 |
likely | |||
Page: 3.0 |
likely | |||
Page: 3.0 |
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
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Page: 52.0 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. | 2015-05-18 |
|
| The role of bendamustine in the treatment of indolent non-Hodgkin lymphoma. | 2009-11-12 |
|
| Bendamustine is effective in p53-deficient B-cell neoplasms and requires oxidative stress and caspase-independent signaling. | 2008-11-01 |
|
| Bendamustine HCL for the treatment of relapsed indolent non-Hodgkin's lymphoma. | 2008-08 |
|
| Weekly administration of bendamustine as salvage therapy in metastatic breast cancer: final results of a phase II study. | 2007-09 |
|
| Bendamustine hydrochloride in patients with refractory soft tissue sarcoma: a noncomparative multicenter phase 2 study of the German sarcoma group (AIO-001). | 2007-08-15 |
|
| Recurrent chemotherapy-induced tumor lysis syndrome (TLS) with renal failure in a patient with chronic lymphocytic leukemia - successful treatment and prevention of TLS with low-dose rasburicase. | 2005-12 |
|
| Upon drug-induced apoptosis in lymphoma cells X-linked inhibitor of apoptosis (XIAP) translocates from the cytosol to the nucleus. | 2004-07 |
|
| Synergistic effects of chemotherapeutic drugs in lymphoma cells are associated with down-regulation of inhibitor of apoptosis proteins (IAPs), prostate-apoptosis-response-gene 4 (Par-4), death-associated protein (Daxx) and with enforced caspase activation. | 2003-09-01 |
|
| Bendamustine monotherapy in advanced and refractory chronic lymphocytic leukemia. | 2001-01 |
|
| Toxicity of the alkylating agent bendamustin. | 1985 |
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12357363
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.
| Substance Class |
Chemical
Created
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admin
on
Edited
Mon Mar 31 18:11:41 GMT 2025
by
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Mon Mar 31 18:11:41 GMT 2025
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| Record UNII |
981Y8SX18M
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| Record Status |
Validated (UNII)
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| Record Version |
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| Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
244807
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NCI_THESAURUS |
C697
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FDA ORPHAN DRUG |
386612
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FDA ORPHAN DRUG |
253107
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QQ-55
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m2306
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DTXSID40188912
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SUB00696MIG
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1065221
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77082
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C61565
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100000085013
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1114693
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3543-75-7
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981Y8SX18M
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981Y8SX18M
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CHEMBL487253
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138783
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DBSALT001167
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
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IMPURITY -> PARENT |
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IMPURITY -> PARENT |
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