Identification

Name
Bendamustine
Accession Number
DB06769
Type
Small Molecule
Groups
Approved, Investigational
Description

Bendamustine is a nitrogen mustard drug indicated for use in the treatment of chronic lymphocytic leukemia (CLL) and 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 capable of forming electrophilic alkyl groups that covalently bond to other molecules. Through this function as an alkylating agent, bendamustine causes intra- and inter-strand crosslinks between DNA bases resulting in cell death. It is active against both active and quiescent cells, although the exact mechanism of action is unknown.

Structure
Thumb
Synonyms
  • Ribomustine
External IDs
SDX 105 / SDX-105 / SDX105
Product Ingredients
IngredientUNIICASInChI Key
Bendamustine hydrochloride981Y8SX18M3543-75-7ZHSKUOZOLHMKEA-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BendekaInjection, solution25 mg/mLIntravenousTeva2015-12-08Not applicableUs
TreandaPowder, for solution25 mgIntravenousLundbeck Inc.2012-09-12Not applicableCanada
TreandaInjection, solution, concentrate45 mg/.5mLIntravenousCephalon2014-11-052017-10-07Us
TreandaInjection, powder, lyophilized, for solution100 mg/20mLIntravenousCephalon2008-03-31Not applicableUs
TreandaPowder, for solution100 mgIntravenousLundbeck Inc.2012-09-12Not applicableCanada
TreandaInjection, solution, concentrate180 mg/2mLIntravenousCephalon2014-11-052017-10-07Us
TreandaInjection, powder, lyophilized, for solution25 mg/5mLIntravenousCephalon2010-01-05Not applicableUs
International/Other Brands
Levact (NAPP Pharmaceuticals ) / Treakisym (Teva Pharmaceutical Industries Ltd.)
Categories
UNII
9266D9P3PQ
CAS number
16506-27-7
Weight
Average: 358.263
Monoisotopic: 357.101082345
Chemical Formula
C16H21Cl2N3O2
InChI Key
YTKUWDBFDASYHO-UHFFFAOYSA-N
InChI
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)
IUPAC Name
4-{5-[bis(2-chloroethyl)amino]-1-methyl-1H-1,3-benzodiazol-2-yl}butanoic acid
SMILES
CN1C(CCCC(O)=O)=NC2=CC(=CC=C12)N(CCCl)CCCl

Pharmacology

Indication

Bendamustine is indicated for use in the treatment of chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.

Structured Indications
Pharmacodynamics

No mean changes in QTc interval greater than 20 milliseconds were detected up to one hour post-infusion.

Mechanism of action

Bendamustine is a bifunctional mechlorethamine derivative capable of forming electrophilic alkyl groups that covalently bond to other molecules. Through this function as an alkylating agent, bendamustine causes intra- and inter-strand crosslinks between DNA bases resulting in cell death. It is active against both active and quiescent cells, although the exact mechanism of action is unknown.

Absorption

Following a single IV dose of bendamustine hydrochloride Cmax typically occurred at the end of infusion. The dose proportionality of bendamustine has not been studied.

Volume of distribution

The mean steady-state volume of distribution (Vss) of bendamustine was approximately 20-25 L. Steady-state volume of distribution for total radioactivity was approximately 50 L, indicating that neither bendamustine nor total radioactivity are extensively distributed into the tissues.

Protein binding

In vitro, the binding of bendamustine to human serum plasma proteins ranged from 94-96% and data suggest that bendamustine is not likely to displace or to be displaced by highly protein-bound drugs.

Metabolism

In vitro data indicate that bendamustine is primarily metabolized via hydrolysis to monohydroxy (HP1) and dihydroxy-bendamustine (HP2) metabolites with low cytotoxic activity. Two active minor metabolites, M3 and M4, are primarily formed via CYP1A2. However, concentrations of these metabolites in plasma are 1/10th and 1/100th that of the parent compound, respectively, suggesting that the cytotoxic activity is primarily due to bendamustine. Results of a human mass balance study confirm that bendamustine is extensively metabolized via hydrolytic, oxidative, and conjugative pathways.

Route of elimination

Mean recovery of total radioactivity in cancer patients following IV infusion of [14C] bendamustine hydrochloride was approximately 76% of the dose. Approximately 50% of the dose was recovered in the urine and approximately 25% of the dose was recovered in the feces. Urinary excretion was confirmed as a relatively minor pathway of elimination of bendamustine, with approximately 3.3% of the dose recovered in the urine as parent. Less than 1% of the dose was recovered in the urine as M3 and M4, and less than 5% of the dose was recovered in the urine as HP2.

Half life

40 minutes

Clearance

700 mL/min

Toxicity

Risk for tumor-lysis syndrome. Discontinue use in the event of severe/progressive skin reactions. Hematologic malignancies of different forms reported. Discontinue use in the case of severe infusion reactions. May cause extravasation. Mild to moderate renal impairment. Mild hepatic impairment. Sepsis (infections) may occur. Avoid use if pregnant. Possibility of anaphylaxis or infusion reactions- severe in rare cases.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Bendamustine can be increased when it is combined with Abiraterone.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Bendamustine.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Bendamustine.Experimental
AllopurinolThe risk or severity of adverse effects can be increased when Allopurinol is combined with Bendamustine.Approved
AzithromycinThe metabolism of Bendamustine can be decreased when combined with Azithromycin.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Bendamustine.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Bendamustine.Approved, Investigational
BortezomibThe metabolism of Bendamustine can be decreased when combined with Bortezomib.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Bendamustine.Approved
CaffeineThe metabolism of Bendamustine can be decreased when combined with Caffeine.Approved
CitalopramThe metabolism of Bendamustine can be decreased when combined with Citalopram.Approved
ClotrimazoleThe metabolism of Bendamustine can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe risk or severity of adverse effects can be increased when Bendamustine is combined with Clozapine.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Bendamustine.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Bendamustine.Experimental
Cyproterone acetateThe serum concentration of Bendamustine can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DeferasiroxThe serum concentration of Bendamustine can be increased when it is combined with Deferasirox.Approved, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of Bendamustine.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Bendamustine.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Bendamustine.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Bendamustine.Approved, Investigational
DosulepinThe serum concentration of Bendamustine can be increased when it is combined with Dosulepin.Approved
FluvoxamineThe serum concentration of Bendamustine can be increased when it is combined with Fluvoxamine.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Bendamustine.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Bendamustine.Experimental
LidocaineThe metabolism of Bendamustine can be decreased when combined with Lidocaine.Approved, Vet Approved
LobeglitazoneThe metabolism of Bendamustine can be decreased when combined with Lobeglitazone.Approved, Investigational
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Bendamustine.Investigational, Withdrawn
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Bendamustine.Experimental
MexiletineThe serum concentration of Bendamustine can be increased when it is combined with Mexiletine.Approved
MidostaurinThe serum concentration of Bendamustine can be increased when it is combined with Midostaurin.Approved
NevirapineThe metabolism of Bendamustine can be decreased when combined with Nevirapine.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Bendamustine.Experimental, Investigational
OsimertinibThe serum concentration of Bendamustine can be decreased when it is combined with Osimertinib.Approved
OuabainOuabain may decrease the cardiotoxic activities of Bendamustine.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Bendamustine.Approved, Vet Approved
Peginterferon alfa-2bThe serum concentration of Bendamustine can be increased when it is combined with Peginterferon alfa-2b.Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Bendamustine.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Bendamustine.Experimental
RopiniroleThe metabolism of Bendamustine can be decreased when combined with Ropinirole.Approved, Investigational
SimeprevirThe metabolism of Bendamustine can be decreased when combined with Simeprevir.Approved
Tenofovir disoproxilThe metabolism of Bendamustine can be decreased when combined with Tenofovir disoproxil.Approved, Investigational
TeriflunomideThe serum concentration of Bendamustine can be decreased when it is combined with Teriflunomide.Approved
TheophyllineThe metabolism of Bendamustine can be decreased when combined with Theophylline.Approved
TiclopidineThe metabolism of Bendamustine can be decreased when combined with Ticlopidine.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Bendamustine.Approved, Investigational
VemurafenibThe serum concentration of Bendamustine can be increased when it is combined with Vemurafenib.Approved
ZucapsaicinThe metabolism of Bendamustine can be decreased when combined with Zucapsaicin.Approved
Food Interactions
Not Available

References

General References
  1. Hartmann JT, Mayer F, Schleicher J, Horger M, Huober J, Meisinger I, Pintoffl J, Kafer G, Kanz L, Grunwald V: Bendamustine hydrochloride in patients with refractory soft tissue sarcoma: a noncomparative multicenter phase 2 study of the German sarcoma group (AIO-001). Cancer. 2007 Aug 15;110(4):861-6. [PubMed:17599772]
  2. Bagchi S: Bendamustine for advanced sarcoma. Lancet Oncol. 2007 Aug;8(8):674. [PubMed:17726779]
  3. Dennie TW, Kolesar JM: Bendamustine for the treatment of chronic lymphocytic leukemia and rituximab-refractory, indolent B-cell non-Hodgkin lymphoma. Clin Ther. 2009;31 Pt 2:2290-311. doi: 10.1016/j.clinthera.2009.11.031. [PubMed:20110042]
  4. Teichert J, Baumann F, Chao Q, Franklin C, Bailey B, Hennig L, Caca K, Schoppmeyer K, Patzak U, Preiss R: Characterization of two phase I metabolites of bendamustine in human liver microsomes and in cancer patients treated with bendamustine hydrochloride. Cancer Chemother Pharmacol. 2007 May;59(6):759-70. Epub 2006 Sep 7. [PubMed:16957931]
  5. Darwish M, Bond M, Hellriegel E, Robertson P Jr, Chovan JP: Pharmacokinetic and pharmacodynamic profile of bendamustine and its metabolites. Cancer Chemother Pharmacol. 2015 Jun;75(6):1143-54. doi: 10.1007/s00280-015-2727-6. Epub 2015 Apr 1. [PubMed:25829094]
External Links
KEGG Drug
D07085
PubChem Compound
65628
PubChem Substance
310264882
ChemSpider
59069
BindingDB
173621
ChEBI
135515
ChEMBL
CHEMBL487253
Wikipedia
Bendamustine
ATC Codes
L01AA09 — Bendamustine
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (170 KB)
MSDS
Download (174 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentMalignant Lymphomas1
0RecruitingTreatmentMalignant Lymphomas / Mantle Cell Lymphoma (MCL)1
1Active Not RecruitingTreatmentB Chronic Lymphocytic Leukemia / Chronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
1Active Not RecruitingTreatmentB-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma / B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma / B-Cell Prolymphocytic Leukemia / Post-Transplant Lymphoproliferative Disorder / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Lymphoplasmacytic Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Small Lymphocytic Lymphoma / Refractory Chronic Lymphocytic Leukemia / Refractory Hairy Cell Leukemia1
1Active Not RecruitingTreatmentB-cell Non-Hodgkin's Lymphomas / Chronic Lymphocytic Leukaemia (CLL)1
1Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Lymphocytic Leukemia, Chronic1
1Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
1Active Not RecruitingTreatmentDiffuse Large B-Cell Lymphoma, Lymphoma Follicular / Diffuse Large B-Cell Lymphoma, Lymphoma, Follicular1
1Active Not RecruitingTreatmentExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Nodal marginal zone B-cell lymphomas / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Splenic Marginal Zone Lymphoma / Waldenstrom's Macroglobulinemia (WM)1
1Active Not RecruitingTreatmentLeukemias1
1Active Not RecruitingTreatmentLeukemias / Malignant Lymphomas1
1Active Not RecruitingTreatmentMetastatic Cancers / Unspecified Adult Solid Tumor, Protocol Specific1
1Active Not RecruitingTreatmentMultiple Myeloma (MM)1
1Active Not RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
1Active Not RecruitingTreatmentPlasma Cell Myeloma1
1Active Not RecruitingTreatmentRefractory/Relapsed Indolent Non-Hodgkin Lymphoma1
1CompletedNot AvailableCancer Which Has Either Progressed or Relapsed After Standard Therapy, or for Which no Curative or Standard Therapy is Appropriate1
1CompletedTreatmentB-cell Small Lymphocytic Lymphoma Recurrent1
1CompletedTreatmentCancer, Advanced1
1CompletedTreatmentCancers1
1CompletedTreatmentChronic Lymphocytic Leukaemia (CLL)1
1CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Indolent Non-Hodgkin's Lymphomas / Mantle Cell Lymphoma (MCL)1
1CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Malignant Lymphomas / Non-Hodgkin's Lymphoma (NHL) / T-Cell Lymphomas1
1CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Non-Hodgkin's Lymphoma (NHL)1
1CompletedTreatmentFollicular Lymphoma (FL) / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Mantle Cell Lymphoma (MCL) / Non-Hodgkin's Lymphoma (NHL)1
1CompletedTreatmentLeukaemia, Acute / Lymphoma, Hodgkins / Non-Hodgkin's Lymphoma (NHL)1
1CompletedTreatmentLymphocytic Leukemia, Chronic1
1CompletedTreatmentMalignancies1
1CompletedTreatmentMetastatic Breast Cancer (MBC)1
1CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)2
1CompletedTreatmentPlasma Cell Myeloma1
1RecruitingTreatmentAdult Lymphocyte Depletion Hodgkin Lymphoma / Adult Lymphocyte Predominant Hodgkin Lymphoma / Adult Mixed Cellularity Hodgkin Lymphoma / Adult Nasal Type Extranodal NK/T-Cell Lymphoma / Adult Nodular Sclerosis Hodgkin Lymphoma / Anaplastic Large Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / Hepatosplenic T-Cell Lymphoma / Noncutaneous Extranodal Lymphoma / Peripheral T-Cell Lymphoma (PTCL) / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Hodgkin's Lymphoma / Recurrent Adult T-Cell Leukemia/Lymphoma / Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Mycosis Fungoides/Sezary Syndrome / T-cell Adult Acute Lymphoblastic Leukemia / T-Cell Large Granular Lymphocyte Leukemia1
1RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Non-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentFollicular Lymphoma (FL) / Lymphoma, B-Cell, Marginal Zone / Lymphoma, Mantle-Cell / Lymphoma, Small-Cell / Non-Hodgkin's Lymphoma (NHL) / Waldenstrom's Macroglobulinemia (WM)1
1RecruitingTreatmentHigh-risk Tumor / Malignant Lymphomas / Neuroblastomas1
1RecruitingTreatmentMalignant Lymphomas / Non-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentMantle Cell Lymphoma (MCL)1
1RecruitingTreatmentMultiple Myeloma (MM) / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Hodgkin's Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Refractory Chronic Lymphocytic Leukemia1
1RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentRelapsed or Refractory Follicular Lymphoma1
1TerminatedTreatmentB-cell Adult Acute Lymphoblastic Leukemia / B-Cell Chronic Lymphocytic Leukemia / Cutaneous B-Cell Non-Hodgkin Lymphoma / Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Intraocular Lymphoma / Nodal marginal zone B-cell lymphomas / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Diffuse Small Cleaved Cell Lymphoma / Recurrent Adult Grade III Lymphomatoid Granulomatosis / Recurrent Adult Immunoblastic Large Cell Lymphoma / Recurrent Adult Lymphoblastic Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Mycosis Fungoides/Sezary Syndrome / Recurrent Small Lymphocytic Lymphoma / Refractory Chronic Lymphocytic Leukemia / Refractory Hairy Cell Leukemia / Small Intestine Lymphoma / Splenic Marginal Zone Lymphoma / Testicular Lymphoma / Waldenstrom's Macroglobulinemia (WM)1
1TerminatedTreatmentMetastatic Brain Tumors1
1TerminatedTreatmentRecurrent Small Lymphocytic Lymphoma / Refractory Chronic Lymphocytic Leukemia / Stage III Chronic Lymphocytic Leukemia / Stage III Small Lymphocytic Lymphoma / Stage IV Chronic Lymphocytic Leukemia / Stage IV Small Lymphocytic Lymphoma1
1WithdrawnTreatmentChronic Lymphocytic Leukaemia (CLL)1
1WithdrawnTreatmentLeukemia, Plasma Cell / Multiple Myeloma (MM)1
1, 2Active Not RecruitingTreatmentAdult Lymphocyte Depletion Hodgkin Lymphoma / Adult Lymphocyte Predominant Hodgkin Lymphoma / Adult Mixed Cellularity Hodgkin Lymphoma / Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma / Adult Nodular Sclerosis Hodgkin Lymphoma / Recurrent Adult Hodgkin's Lymphoma1
1, 2Active Not RecruitingTreatmentAnaplastic Large Cell Lymphoma / Lymphoma, Hodgkins1
1, 2Active Not RecruitingTreatmentDiffuse Large B-Cell Lymphoma, Lymphoma, Non Hodgkin, Lymphoma, Follicular / Malignant Lymphomas1
1, 2Active Not RecruitingTreatmentHodgkins Disease (HD)1
1, 2Active Not RecruitingTreatmentLeukemia, Lymphocytic, Chronic, B-Cell1
1, 2Active Not RecruitingTreatmentMantle Cell Lymphoma (MCL)1
1, 2Active Not RecruitingTreatmentMultiple Myeloma (MM)2
1, 2Active Not RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
1, 2Active Not RecruitingTreatmentRecurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Hodgkin's Lymphoma1
1, 2Active Not RecruitingTreatmentRecurrent Adult Hodgkin's Lymphoma1
1, 2Active Not RecruitingTreatmentRefractory Multiple Myeloma1
1, 2CompletedTreatmentAdult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / De Novo Myelodysplastic Syndromes / Myelodysplastic Syndrome With Isolated Del(5q) / Untreated Adult Acute Myeloid Leukemia1
1, 2CompletedTreatmentAdult B Acute Lymphoblastic Leukemia / Adult Nasal Type Extranodal NK/T-Cell Lymphoma / Adult Solid Neoplasm / Anaplastic Large Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / Chronic Lymphocytic Leukaemia (CLL) / Cutaneous B-Cell Non-Hodgkin Lymphoma / Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue / Hepatosplenic T-Cell Lymphoma / Intraocular Lymphoma / Lymphomatous Involvement of Non-Cutaneous Extranodal Site / Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma / Nodal Marginal Zone Lymphoma / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Diffuse Small Cleaved Cell Lymphoma / Recurrent Adult Grade III Lymphomatoid Granulomatosis / Recurrent Adult Hodgkin's Lymphoma / Recurrent Adult Immunoblastic Lymphoma / Recurrent Adult Lymphoblastic Lymphoma / Recurrent Adult T-Cell Leukemia/Lymphoma / Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Mycosis Fungoides and Sezary Syndrome / Recurrent Small Lymphocytic Lymphoma / Refractory Chronic Lymphocytic Leukemia / Refractory Hairy Cell Leukemia / Refractory Plasma Cell Myeloma / Small Intestinal Lymphoma / Splenic Marginal Zone Lymphoma / Testicular Lymphoma / Waldenstrom's Macroglobulinemia (WM)1
1, 2CompletedTreatmentCancer, Breast1
1, 2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL)2
1, 2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Recurrent Small Lymphocytic Lymphoma / Refractory Chronic Lymphocytic Leukemia1
1, 2CompletedTreatmentLeukemias2
1, 2CompletedTreatmentMalignant Lymphomas1
1, 2CompletedTreatmentMultiple Myeloma (MM)1
1, 2CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)1
1, 2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Myelogenous Leukaemia (AML) / Burkitt's Lymphoma / Chronic Myelogenous Leukemia (CML) / Follicular Lymphoma (FL) / Gray Zone Lymphoma / Juvenile Myelomonocytic Leukemia / Lymphoma, Hodgkins / Lymphoma, Large Cell / Lymphoma, Mantle-Cell / Lymphoma,Non-Hodgkin / Marginal Zone Lymphoma / Myelodysplastic Syndromes1
1, 2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemia Acute Myeloid Leukemia (AML) / Mixed-Lineage Acute Leukemias1
1, 2RecruitingTreatmentClinical Efficacy / Safety1
1, 2RecruitingTreatmentLeukemia, Lymphocytic, Chronic, B-Cell / Malignant Lymphomas1
1, 2RecruitingTreatmentLeukemias / Malignant Lymphomas1
1, 2RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
1, 2RecruitingTreatmentMultiple Myeloma (MM)2
1, 2RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
1, 2TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Chronic Myeloid Leukemia (CML) / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
1, 2Unknown StatusTreatmentLymphoma, Mantle-Cell1
1, 2Unknown StatusTreatmentMultiple Myeloma (MM)3
1, 2WithdrawnTreatmentExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Nodal marginal zone B-cell lymphomas / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Splenic Marginal Zone Lymphoma1
1, 2WithdrawnTreatmentMantle Cell Lymphoma (MCL)1
2Active Not RecruitingTreatmentAL Amyloidosis1
2Active Not RecruitingTreatmentAdult Anaplastic Astrocytoma / Adult Anaplastic Oligodendroglioma / Adult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma / Recurrent Adult Brain Neoplasm / Recurrent Adult Brain Tumor1
2Active Not RecruitingTreatmentCancer, Breast1
2Active Not RecruitingTreatmentChronic Lymphocytic Leucemia2
2Active Not RecruitingTreatmentChronic Lymphocytic Leucemia / Chronic Lymphocytic Leukaemia (CLL)1
2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)3
2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias1
2Active Not RecruitingTreatmentFollicular Lymphoma (FL)1
2Active Not RecruitingTreatmentFollicular Lymphoma (FL) / Relapsed or Refractory Follicular Lymphoma1
2Active Not RecruitingTreatmentGrade 3a Follicular Lymphoma / Stage III Grade 1 Follicular Lymphoma / Stage III Grade 2 Follicular Lymphoma / Stage III Grade 3 Follicular Lymphoma / Stage IV Grade 1 Follicular Lymphoma / Stage IV Grade 2 Follicular Lymphoma / Stage IV Grade 3 Follicular Lymphoma1
2Active Not RecruitingTreatmentLeukemias / Malignant Lymphomas1
2Active Not RecruitingTreatmentMantle Cell Lymphoma (MCL)2
2Active Not RecruitingTreatmentMarginal Zone B-Cell Lymphoma1
2Active Not RecruitingTreatmentMultiple Myeloma (MM)2
2Active Not RecruitingTreatmentStage I Multiple Myeloma / Stage II Multiple Myeloma / Stage III Multiple Myeloma1
2Active Not RecruitingTreatmentT-Cell Lymphomas1
2CompletedTreatmentAdult Nasal Type Extranodal NK/T-Cell Lymphoma / Anaplastic Large Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / Cutaneous B-Cell Non-Hodgkin Lymphoma / Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Intraocular Lymphoma / Nodal marginal zone B-cell lymphomas / Peripheral T-Cell Lymphoma (PTCL) / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Diffuse Small Cleaved Cell Lymphoma / Recurrent Adult Grade III Lymphomatoid Granulomatosis / Recurrent Adult Hodgkin's Lymphoma / Recurrent Adult Immunoblastic Large Cell Lymphoma / Recurrent Adult Lymphoblastic Lymphoma / Recurrent Adult T-Cell Leukemia/Lymphoma / Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Mycosis Fungoides/Sezary Syndrome / Recurrent Small Lymphocytic Lymphoma / Refractory Multiple Myeloma / Small Intestine Lymphoma / Splenic Marginal Zone Lymphoma / Waldenstrom's Macroglobulinemia (WM)1
2CompletedTreatmentAutoimmune Hemolytic Anemia / Cold type haemolytic anaemia1
2CompletedTreatmentCancer, Ovarian1
2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL)2
2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemia, Lymphocytic, Chronic1
2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias2
2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
2CompletedTreatmentDiffuse, Mantle Cell Lymphoma, Lymphoma / Follicular Lymphoma (FL) / Large B-Cell, Diffuse / Lymphoma, Large Cell / Non-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentFollicular B-cell Non-Hodgkin's Lymphoma / Refractory Diffuse Large B Cell Lymphoma1
2CompletedTreatmentFollicular Lymphoma (FL)2
2CompletedTreatmentHodgkins Disease (HD) / Malignant Lymphomas1
2CompletedTreatmentIndolent Non-follicular / Non-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentLung Cancers1
2CompletedTreatmentLymphoma, Diffuse Large-Cell / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Malignant Lymphomas1
2CompletedTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)3
2CompletedTreatmentLymphoma, Mantle-Cell1
2CompletedTreatmentMALT Lymphoma1
2CompletedTreatmentMalignant Lymphomas2
2CompletedTreatmentMantle Cell Lymphoma (MCL)1
2CompletedTreatmentMantle Cell Lymphoma (MCL) / Non-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentMultiple Myeloma (MM)4
2CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)5
2CompletedTreatmentPatients With CLL Refractory (SD, PD or CR/PR < 6 Months) Following no More Than Two Prior Treatment Lines / Patients With CLL Relapsing After an Initial Response (CR, PR ≥ 6 Months) Following no More Than Two Prior Treatment Lines; or1
2CompletedTreatmentT-Cell Lymphomas1
2Not Yet RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2RecruitingTreatmentAggressive Lymphoma1
2RecruitingTreatmentChronic Kidney Disease (CKD) / Multiple Myeloma (MM)1
2RecruitingTreatmentChronic Lymphocytic Leucemia2
2RecruitingTreatmentClassical Hodgkin Lymphoma1
2RecruitingTreatmentFollicular Lymphoma (FL)1
2RecruitingTreatmentHairy Cell Leukemia (HCL)1
2RecruitingTreatmentHodgkins Disease (HD)2
2RecruitingTreatmentLeukemia, Lymphocytic / Non-Hodgkin's Lymphoma (NHL) / Small Lymphocytic Lymphoma (SLL)1
2RecruitingTreatmentLymphatic Diseases1
2RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2RecruitingTreatmentMalignant Lymphomas / Neurotoxicity / Therapy-Related Toxicity1
2RecruitingTreatmentMantle Cell Lymphoma (MCL) / Non Hodgkin Lymphoma (NHL) / Non-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentMultiple Myeloma (MM)3
2RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentRelapsed/Refractory Malignant Lymphomas1
2TerminatedTreatmentChronic Lymphocytic Leukaemia (CLL)1
2TerminatedTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
2TerminatedTreatmentFollicular Lymphoma (FL)2
2TerminatedTreatmentMalignant Lymphomas1
2Unknown StatusTreatmentFollicular Non-Hodgking´s Lymphoma Refractory or Relapsed After Treatment With R-chemotherapy in First Line1
2Unknown StatusTreatmentLymphoma, High-Grade1
2Unknown StatusTreatmentLymphoma, Hodgkins1
2Unknown StatusTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2Unknown StatusTreatmentMalignant Lymphomas1
2Unknown StatusTreatmentMultiple Myeloma (MM)1
2Unknown StatusTreatmentNon-Hodgkin's Lymphoma (NHL)1
2WithdrawnTreatmentChronic Lymphocytic Leukaemia (CLL)2
2WithdrawnTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
2WithdrawnTreatmentFollicular Lymphoma (FL) / Grey Zone Lymphoma / High Grade B Cell Lymphoma / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Marginal Zone Lymphoma / Mediastinal Large B-cell Lymphoma / Small Lymphocytic Lymphoma (SLL)1
2WithdrawnTreatmentLeukemias1
2WithdrawnTreatmentLeukemias / Malignant Lymphomas1
2WithdrawnTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2WithdrawnTreatmentPlasma Cell Myeloma1
2, 3CompletedTreatmentChronic Lymphocytic Leukaemia (CLL)1
2, 3RecruitingTreatmentFollicular Lymphoma (FL) / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Marginal Zone Lymphoma / Small Lymphocytic Lymphoma (SLL)1
2, 3RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
3Active Not RecruitingTreatmentCD19 Positive / CD20 Positive / CD5 Positive / Stage I Chronic Lymphocytic Leukemia / Stage II Chronic Lymphocytic Leukemia / Stage III Chronic Lymphocytic Leukemia / Stage IV Chronic Lymphocytic Leukemia1
3Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)3
3Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias1
3Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
3Active Not RecruitingTreatmentFollicular Lymphoma (FL)1
3Active Not RecruitingTreatmentMalignant Lymphomas2
3Active Not RecruitingTreatmentMantle Cell Lymphoma (MCL)1
3Active Not RecruitingTreatmentMantle Cell Lymphoma (MCL) / Non-Hodgkin's Lymphoma (NHL)1
3Active Not RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)3
3CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Indolent Non-Hodgkin's Lymphomas1
3CompletedTreatmentDiffuse Large B-Cell Lymphoma, Non-Hodgkin's Lymphoma1
3CompletedTreatmentFollicular Lymphoma (FL) / Immunocytomas / Lymphocytic Lymphomas / Marginal Zone Lymphomas / Non-Hodgkin's Lymphoma (NHL)1
3CompletedTreatmentMantle Cell Lymphoma (MCL) / Non-Hodgkin's Lymphoma (NHL)1
3CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)1
3RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)3
3RecruitingTreatmentChronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma1
3RecruitingTreatmentFollicular Lymphoma (FL)1
3RecruitingTreatmentFollicular Non-Hodgkin's Lymphoma1
3RecruitingTreatmentIndolent B-cell NHL1
3RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
3RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
3TerminatedTreatmentChronic Lymphocytic Leukaemia (CLL)1
3TerminatedTreatmentIndolent Non-Hodgkin's Lymphomas1
3TerminatedTreatmentNon-Hodgkin's Lymphoma (NHL)1
3Unknown StatusTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias / Neoplasms1
3Unknown StatusTreatmentNon-Hodgkin Lymphoma by Clinical Course1
3WithdrawnTreatmentFollicular Lymphoma (FL) / Indolent Non-Hodgkin's Lymphomas / Marginal Zone Lymphoma / Small Lymphocytic Lymphoma (SLL)1
4CompletedTreatmentLymphocytic Leukemia, Chronic1
4WithdrawnNot AvailableChronic Lymphocytic Leukaemia (CLL)1
Not AvailableActive Not RecruitingNot AvailableChronic Lymphocytic Leukaemia (CLL)1
Not AvailableCompletedNot AvailableRelapsed or Refractory Chronic Lymphoproliferative Disorders1
Not AvailableRecruitingNot AvailableChronic Lymphocytic Leukaemia (CLL)1
Not AvailableRecruitingTreatmentLymphoma, Hodgkins / Non-Hodgkin's Lymphoma (NHL)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionIntravenous25 mg/mL
Injection, powder, lyophilized, for solutionIntravenous100 mg/20mL
Injection, powder, lyophilized, for solutionIntravenous25 mg/5mL
Injection, solution, concentrateIntravenous180 mg/2mL
Injection, solution, concentrateIntravenous45 mg/.5mL
Powder, for solutionIntravenous100 mg
Powder, for solutionIntravenous25 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8791270Yes2006-07-122026-07-12Us
US8344006Yes2010-03-232030-03-23Us
US8445524Yes2009-09-262029-09-26Us
US8669279Yes2009-09-262029-09-26Us
US8883836Yes2009-09-262029-09-26Us
US8436190Yes2011-04-262031-04-26Us
US8895756Yes2006-07-122026-07-12Us
US8609863Yes2006-07-122026-07-12Us
US9034908No2013-03-152033-03-15Us
US9144568No2013-03-152033-03-15Us
US9000021No2013-03-152033-03-15Us
US8609707No2011-08-112031-08-11Us
US9265831No2011-01-282031-01-28Us
US9533955No2009-03-262029-03-26Us
US9597397No2013-03-152033-03-15Us
US9597399No2013-03-152033-03-15Us
US9597398No2013-03-152033-03-15Us
US9579384No2013-03-152033-03-15Us
US9572797No2011-01-282031-01-28Us
US9572796No2011-01-282031-01-28Us
US9572887No2013-03-152033-03-15Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0618 mg/mLALOGPS
logP3.07ALOGPS
logP1.66ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)4.38ChemAxon
pKa (Strongest Basic)6.65ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area58.36 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity92.92 m3·mol-1ChemAxon
Polarizability38.19 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9947
Blood Brain Barrier+0.773
Caco-2 permeable+0.5348
P-glycoprotein substrateSubstrate0.6887
P-glycoprotein inhibitor INon-inhibitor0.8236
P-glycoprotein inhibitor IINon-inhibitor0.7294
Renal organic cation transporterNon-inhibitor0.5462
CYP450 2C9 substrateNon-substrate0.7141
CYP450 2D6 substrateNon-substrate0.7322
CYP450 3A4 substrateSubstrate0.5545
CYP450 1A2 substrateNon-inhibitor0.8012
CYP450 2C9 inhibitorNon-inhibitor0.9027
CYP450 2D6 inhibitorNon-inhibitor0.878
CYP450 2C19 inhibitorNon-inhibitor0.8587
CYP450 3A4 inhibitorNon-inhibitor0.8756
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8882
Ames testNon AMES toxic0.618
CarcinogenicityNon-carcinogens0.9235
BiodegradationNot ready biodegradable0.9798
Rat acute toxicity3.2636 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7196
hERG inhibition (predictor II)Non-inhibitor0.7584
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzimidazoles. These are organic compounds containing a benzene ring fused to an imidazole ring (five member ring containing a nitrogen atom, 4 carbon atoms, and two double bonds).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzimidazoles
Sub Class
Not Available
Direct Parent
Benzimidazoles
Alternative Parents
Nitrogen mustard compounds / Dialkylarylamines / N-substituted imidazoles / Benzenoids / Heteroaromatic compounds / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds
show 5 more
Substituents
Benzimidazole / Dialkylarylamine / Tertiary aliphatic/aromatic amine / Nitrogen mustard / Benzenoid / N-substituted imidazole / Azole / Heteroaromatic compound / Imidazole / Amino acid or derivatives
show 20 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Teichert J, Baumann F, Chao Q, Franklin C, Bailey B, Hennig L, Caca K, Schoppmeyer K, Patzak U, Preiss R: Characterization of two phase I metabolites of bendamustine in human liver microsomes and in cancer patients treated with bendamustine hydrochloride. Cancer Chemother Pharmacol. 2007 May;59(6):759-70. Epub 2006 Sep 7. [PubMed:16957931]

Drug created on September 14, 2010 10:21 / Updated on November 14, 2017 08:11