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Identification
NameBortezomib
Accession NumberDB00188  (APRD00828, DB07475)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Bortezomib (originally PS-341 and marketed as Velcade by Millennium Pharmaceuticals) is the first therapeutic proteasome inhibitor to be tested in humans. It is approved in the U.S. for treating relapsed multiple myeloma and mantle cell lymphoma. In multiple myeloma, complete clinical responses have been obtained in patients with otherwise refractory or rapidly advancing disease.

Structure
Thumb
Synonyms
N-[(1R)-1-(DIHYDROXYBORYL)-3-methylbutyl]-N-(pyrazin-2-ylcarbonyl)-L-phenylalaninamide
External Identifiers
  • PS 341
  • PS-341
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act Bortezomibpowder for solution3.5 mgintravenous; subcutaneousActavis Pharma Company2015-11-17Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Bortezomib for Injectionpowder for solution3.5 mgintravenous; subcutaneousTeva Canada Limited2015-01-06Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Velcadeinjection, powder, lyophilized, for solution3.5 mg/1intravenous; subcutaneousMillennium Pharmaceuticals, Inc.2003-05-13Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Velcadepowder for solution3.5 mgintravenous; subcutaneousJanssen Inc2005-02-01Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
CAS number179324-69-7
WeightAverage: 384.237
Monoisotopic: 384.196885774
Chemical FormulaC19H25BN4O4
InChI KeyInChIKey=GXJABQQUPOEUTA-RDJZCZTQSA-N
InChI
InChI=1S/C19H25BN4O4/c1-13(2)10-17(20(27)28)24-18(25)15(11-14-6-4-3-5-7-14)23-19(26)16-12-21-8-9-22-16/h3-9,12-13,15,17,27-28H,10-11H2,1-2H3,(H,23,26)(H,24,25)/t15-,17-/m0/s1
IUPAC Name
[(1R)-3-methyl-1-[(2S)-3-phenyl-2-(pyrazin-2-ylformamido)propanamido]butyl]boronic acid
SMILES
CC(C)C[C@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)C1=CN=CC=N1)B(O)O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-acyl-alpha amino acids and derivatives. These are compounds containing an alpha amino acid (or a derivative thereof) which bears an acyl group at its terminal nitrogen atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentN-acyl-alpha amino acids and derivatives
Alternative Parents
Substituents
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid amide
  • Phenylpropylamine
  • Amphetamine or derivatives
  • Pyrazinecarboxamide
  • Pyrazine carboxylic acid or derivatives
  • Fatty acyl
  • Benzenoid
  • Pyrazine
  • Fatty amide
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Boronic acid
  • Boronic acid derivative
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organic metalloid salt
  • Organooxygen compound
  • Organonitrogen compound
  • Organoboron compound
  • Organic metalloid moeity
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor treatment of multiple myeloma in patients who have not been successfully treated with at least two previous therapies.
PharmacodynamicsBortezomib is a drug that inhibits the mammalian 26S proteasome. The ubiquitin-proteasome pathway plays an essential role in regulating the intracellular concentration of specific proteins, thereby maintaining homeostasis within cells. Inhibition of the 26S proteasome prevents this targeted proteolysis, which can affect multiple signaling cascades within the cell. This disruption of normal homeostatic mechanisms can lead to cell death. Experiments have demonstrated that bortezomib is cytotoxic to a variety of cancer cell types in vitro. Bortezomib causes a delay in tumor growth in vivo in nonclinical tumor models, including multiple myeloma. Tumor cells, that is, rapidly dividing cells, appear to be more sensitive to proteasome inhibition.
Mechanism of actionBortezomib is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome in mammalian cells. The 26S proteasome is a large protein complex that degrades ubiquitinated proteins. The active site of the proteasome has chymotrypsin-like, trypsin-like, and postglutamyl peptide hydrolysis activity. The 26S proteasome degrades various proteins critical to cancer cell survival, such as cyclins, tumor suppressors, BCL-2, and cyclin-dependent kinase inhibitors. Inhibition of these degradations sensitizes cells to apoptosis. Bortezomib is a potent inhibitor of 26S proteasome, which sensitizes activity in dividing multiple myeloma and leukemic cells, thus inducing apoptosis. In addition, bortezomib appears to increase the sensitivity of cancer cells to traditional anticancer agents (e.g., gemcitabine, cisplatin, paclitaxel, irinotecan, and radiation).
AbsorptionNot Available
Volume of distributionNot Available
Protein binding83% over the concentration range of 100-1000 ng/ml.
Metabolism

In vitro studies with human liver microsomes and human cDNA-expressed cytochrome P450 isozymes indicate that bortezomib is primarily oxidatively metabolized via cytochrome P450 enzymes 3A4, 2C19, and 1A2, while bortezomib metabolism by CYP 2D6 and 2C9 enzymes is minor. The major metabolic pathway is deboronation to form 2 deboronated metabolites that subsequently undergo hydroxylation to several metabolites which are inactive as 26S proteasome inhibitors.

SubstrateEnzymesProduct
Bortezomib
Bortezomib metabolite M1Details
Bortezomib
Bortezomib metabolite M2Details
Bortezomib metabolite M1
Not Available
Bortezomib metabolite M3Details
Bortezomib metabolite M2
Not Available
Bortezomib metabolite M3Details
Bortezomib metabolite M3
Not Available
Bortezomib metabolite M4Details
Bortezomib metabolite M1
Not Available
Bortezomib metabolite M5Details
Bortezomib metabolite M2
Not Available
Bortezomib metabolite M6Details
Bortezomib metabolite M2
Bortezomib metabolite M8Details
Bortezomib metabolite M8
Not Available
Bortezomib metabolite M33Details
Bortezomib
Not Available
Bortezomib metabolite M34Details
Bortezomib metabolite M1
Not Available
Bortezomib metabolite M25Details
Bortezomib metabolite M1
Not Available
Bortezomib metabolite M26Details
Bortezomib metabolite M2
Not Available
Bortezomib metabolite M27Details
Bortezomib metabolite M2
Not Available
Bortezomib metabolite M28Details
Bortezomib
Bortezomib metabolite M23 or M24 (1)Details
Bortezomib
Bortezomib metabolite M23 or M24 (2)Details
Route of eliminationThe pathways of elimination of bortezomib have not been characterized in humans.
Half lifeThe mean elimination half-life of bortezomib after first dose ranged from 9 to 15 hours at doses ranging from 1.45 to 2.00 mg/m2 in patients with advanced malignancies.
Clearance
  • 102 L/h [patients with multiple myeloma following the first dose for doses of 1 mg/m2]
  • 112 L/h [patients with multiple myeloma following the first dose for doses of 1.3 mg/m2]
  • 15 – 32 L/h [patients with multiple myeloma following subsequent doses for doses of 1 and 1.3 mg/m2]
ToxicityCardiovascular safety pharmacology studies in monkeys show that lethal IV doses are associated with decreases in blood pressure, increases in heart rate, increases in contractility, and ultimately terminal hypotension. In monkeys, doses of 3.0 mg/m2 and greater (approximately twice the recommended clinical dose) resulted in progressive hypotension starting at 1 hour and progressing to death by 12 to 14 hours following drug administration.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.6935
Blood Brain Barrier-0.6533
Caco-2 permeable-0.6576
P-glycoprotein substrateSubstrate0.5909
P-glycoprotein inhibitor INon-inhibitor0.785
P-glycoprotein inhibitor IINon-inhibitor1.0
Renal organic cation transporterNon-inhibitor0.9445
CYP450 2C9 substrateNon-substrate0.7145
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateNon-substrate0.5209
CYP450 1A2 substrateNon-inhibitor0.855
CYP450 2C9 inhibitorNon-inhibitor0.8267
CYP450 2D6 inhibitorNon-inhibitor0.9304
CYP450 2C19 inhibitorNon-inhibitor0.8108
CYP450 3A4 inhibitorNon-inhibitor0.7308
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9604
Ames testNon AMES toxic0.7439
CarcinogenicityNon-carcinogens0.8064
BiodegradationNot ready biodegradable0.9943
Rat acute toxicity2.4537 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9936
hERG inhibition (predictor II)Non-inhibitor0.8593
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Millennium pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionintravenous; subcutaneous3.5 mg/1
Powder for solutionintravenous; subcutaneous3.5 mg
Prices
Unit descriptionCostUnit
Velcade 3.5 mg vial1590.0USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada22039362005-04-122015-10-27
United States60839031994-10-282014-10-28
United States67134462002-01-252022-01-25
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityThe solubility of bortezomib, as the monomeric boronic acid, is 3.3 to 3.8 mg/mL in a pH range of 2 to 6.5.Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0532 mg/mLALOGPS
logP0.89ALOGPS
logP1.53ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)13.04ChemAxon
pKa (Strongest Basic)-0.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area124.44 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity99.37 m3·mol-1ChemAxon
Polarizability40.48 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Raghavendracharyulu Venkata Palle, Rajasekhar Kadaboina, Veerendeer Murki, Amarendhar Manda, Nageshwar Gunda, Ramaseshagiri Rao Pulla, Mallesha Hanmanthu, Narasimha Naidu Mopidevi, Suresh Kumar Ramdoss, “BORTEZOMIB AND PROCESS FOR PRODUCING SAME.” U.S. Patent US20100226597, issued September 09, 2010.

US20100226597
General References
  1. Adams J, Kauffman M: Development of the proteasome inhibitor Velcade (Bortezomib). Cancer Invest. 2004;22(2):304-11. Pubmed
  2. Bonvini P, Zorzi E, Basso G, Rosolen A: Bortezomib-mediated 26S proteasome inhibition causes cell-cycle arrest and induces apoptosis in CD-30+ anaplastic large cell lymphoma. Leukemia. 2007 Apr;21(4):838-42. Epub 2007 Feb 1. Pubmed
  3. Voorhees PM, Dees EC, O’Neil B, Orlowski RZ: The proteasome as a target for cancer therapy. Clin Cancer Res. 2003 Dec 15;9(17):6316-25. Pubmed
  4. Oakervee HE, Popat R, Curry N, Smith P, Morris C, Drake M, Agrawal S, Stec J, Schenkein D, Esseltine DL, Cavenagh JD: PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma. Br J Haematol. 2005 Jun;129(6):755-62. Pubmed
External Links
ATC CodesL01XX32
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelDownload (199 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Bortezomib can be increased when it is combined with Abiraterone.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Bortezomib.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Bortezomib.
Acetylsalicylic acidThe metabolism of Acetylsalicylic acid can be decreased when combined with Bortezomib.
AlosetronThe metabolism of Alosetron can be decreased when combined with Bortezomib.
AminophyllineThe metabolism of Aminophylline can be decreased when combined with Bortezomib.
AripiprazoleThe serum concentration of Aripiprazole can be increased when it is combined with Bortezomib.
ArmodafinilThe metabolism of Bortezomib can be decreased when combined with Armodafinil.
AsenapineThe metabolism of Asenapine can be decreased when combined with Bortezomib.
AtazanavirThe serum concentration of Bortezomib can be increased when it is combined with Atazanavir.
BetaxololThe metabolism of Betaxolol can be decreased when combined with Bortezomib.
BexaroteneThe serum concentration of Bortezomib can be decreased when it is combined with Bexarotene.
BoceprevirThe serum concentration of Bortezomib can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Bortezomib can be decreased when it is combined with Bosentan.
BromazepamThe metabolism of Bromazepam can be decreased when combined with Bortezomib.
ButalbitalThe metabolism of Butalbital can be decreased when combined with Bortezomib.
CaffeineThe metabolism of Caffeine can be decreased when combined with Bortezomib.
CarbamazepineThe serum concentration of Bortezomib can be decreased when it is combined with Carbamazepine.
CarisoprodolThe metabolism of Carisoprodol can be decreased when combined with Bortezomib.
CeritinibThe serum concentration of Bortezomib can be increased when it is combined with Ceritinib.
ChloramphenicolThe metabolism of Bortezomib can be decreased when combined with Chloramphenicol.
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Bortezomib.
CimetidineThe metabolism of Bortezomib can be decreased when combined with Cimetidine.
CiprofloxacinThe metabolism of Bortezomib can be decreased when combined with Ciprofloxacin.
CitalopramThe serum concentration of Citalopram can be increased when it is combined with Bortezomib.
ClarithromycinThe serum concentration of Bortezomib can be increased when it is combined with Clarithromycin.
ClobazamThe metabolism of Clobazam can be decreased when combined with Bortezomib.
ClomipramineThe metabolism of Clomipramine can be decreased when combined with Bortezomib.
ClopidogrelThe serum concentration of the active metabolites of Clopidogrel can be reduced when Clopidogrel is used in combination with Bortezomib resulting in a loss in efficacy.
ClozapineThe risk or severity of adverse effects can be increased when Bortezomib is combined with Clozapine.
CobicistatThe serum concentration of Bortezomib can be increased when it is combined with Cobicistat.
CyclobenzaprineThe metabolism of Cyclobenzaprine can be decreased when combined with Bortezomib.
Cyproterone acetateThe serum concentration of Bortezomib can be decreased when it is combined with Cyproterone acetate.
DabrafenibThe serum concentration of Bortezomib can be decreased when it is combined with Dabrafenib.
DacarbazineThe metabolism of Dacarbazine can be decreased when combined with Bortezomib.
DarunavirThe serum concentration of Bortezomib can be increased when it is combined with Darunavir.
DeferasiroxThe serum concentration of Bortezomib can be decreased when it is combined with Deferasirox.
DelavirdineThe metabolism of Bortezomib can be decreased when combined with Delavirdine.
DesogestrelThe metabolism of Bortezomib can be decreased when combined with Desogestrel.
DiazepamThe metabolism of Diazepam can be decreased when combined with Bortezomib.
DihydrocodeineThe metabolism of Dihydrocodeine can be decreased when combined with Bortezomib.
DofetilideBortezomib may increase the QTc-prolonging activities of Dofetilide.
DuloxetineThe metabolism of Duloxetine can be decreased when combined with Bortezomib.
EfavirenzThe metabolism of Bortezomib can be decreased when combined with Efavirenz.
EnzalutamideThe serum concentration of Bortezomib can be decreased when it is combined with Enzalutamide.
EscitalopramThe metabolism of Escitalopram can be decreased when combined with Bortezomib.
Eslicarbazepine acetateThe metabolism of Bortezomib can be decreased when combined with Eslicarbazepine acetate.
EsomeprazoleThe metabolism of Bortezomib can be decreased when combined with Esomeprazole.
Ethinyl EstradiolThe metabolism of Bortezomib can be decreased when combined with Ethinyl Estradiol.
EthynodiolThe metabolism of Bortezomib can be decreased when combined with Ethynodiol.
EtravirineThe metabolism of Bortezomib can be decreased when combined with Etravirine.
FluconazoleThe metabolism of Bortezomib can be decreased when combined with Fluconazole.
FluoxetineThe metabolism of Bortezomib can be decreased when combined with Fluoxetine.
FlutamideThe metabolism of Flutamide can be decreased when combined with Bortezomib.
FluvoxamineThe metabolism of Fluvoxamine can be decreased when combined with Bortezomib.
FosphenytoinThe serum concentration of Bortezomib can be decreased when it is combined with Fosphenytoin.
GemfibrozilThe metabolism of Bortezomib can be decreased when combined with Gemfibrozil.
GoserelinBortezomib may increase the QTc-prolonging activities of Goserelin.
IdelalisibThe serum concentration of Bortezomib can be increased when it is combined with Idelalisib.
ImipramineThe metabolism of Imipramine can be decreased when combined with Bortezomib.
IndinavirThe serum concentration of Bortezomib can be increased when it is combined with Indinavir.
IsomethepteneThe metabolism of Isometheptene can be decreased when combined with Bortezomib.
IsoniazidThe metabolism of Bortezomib can be decreased when combined with Isoniazid.
ItraconazoleThe serum concentration of Bortezomib can be increased when it is combined with Itraconazole.
KetoconazoleThe serum concentration of Bortezomib can be increased when it is combined with Ketoconazole.
LeuprolideBortezomib may increase the QTc-prolonging activities of Leuprolide.
LidocaineThe metabolism of Lidocaine can be decreased when combined with Bortezomib.
LopinavirThe metabolism of Bortezomib can be increased when combined with Lopinavir.
LuliconazoleThe serum concentration of Bortezomib can be increased when it is combined with Luliconazole.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Bortezomib.
MethoxsalenThe metabolism of Bortezomib can be decreased when combined with Methoxsalen.
MethsuximideThe metabolism of Methsuximide can be decreased when combined with Bortezomib.
MexiletineThe metabolism of Mexiletine can be decreased when combined with Bortezomib.
MifepristoneMifepristone may increase the QTc-prolonging activities of Bortezomib.
MirtazapineThe metabolism of Mirtazapine can be decreased when combined with Bortezomib.
MitotaneThe serum concentration of Bortezomib can be decreased when it is combined with Mitotane.
MoclobemideThe metabolism of Moclobemide can be decreased when combined with Bortezomib.
ModafinilThe metabolism of Bortezomib can be decreased when combined with Modafinil.
NefazodoneThe serum concentration of Bortezomib can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Bortezomib can be increased when it is combined with Nelfinavir.
NicardipineThe metabolism of Bortezomib can be decreased when combined with Nicardipine.
NilutamideThe metabolism of Nilutamide can be decreased when combined with Bortezomib.
OfloxacinThe metabolism of Bortezomib can be decreased when combined with Ofloxacin.
OlanzapineThe metabolism of Olanzapine can be decreased when combined with Bortezomib.
OmeprazoleThe metabolism of Bortezomib can be decreased when combined with Omeprazole.
OsimertinibThe serum concentration of Bortezomib can be decreased when it is combined with Osimertinib.
PantoprazoleThe metabolism of Pantoprazole can be decreased when combined with Bortezomib.
Peginterferon alfa-2bThe serum concentration of Bortezomib can be increased when it is combined with Peginterferon alfa-2b.
PentamidineThe metabolism of Pentamidine can be decreased when combined with Bortezomib.
PhenobarbitalThe serum concentration of Bortezomib can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Bortezomib can be decreased when it is combined with Phenytoin.
PimozideThe metabolism of Pimozide can be decreased when combined with Bortezomib.
PomalidomideThe metabolism of Pomalidomide can be decreased when combined with Bortezomib.
PosaconazoleThe serum concentration of Bortezomib can be increased when it is combined with Posaconazole.
PrimaquineThe metabolism of Bortezomib can be decreased when combined with Primaquine.
PrimidoneThe serum concentration of Bortezomib can be decreased when it is combined with Primidone.
PropranololThe metabolism of Propranolol can be decreased when combined with Bortezomib.
RamelteonThe metabolism of Ramelteon can be decreased when combined with Bortezomib.
RasagilineThe metabolism of Rasagiline can be decreased when combined with Bortezomib.
RifabutinThe serum concentration of Bortezomib can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Bortezomib can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Bortezomib can be decreased when it is combined with Rifapentine.
RitonavirThe serum concentration of Bortezomib can be increased when it is combined with Ritonavir.
RopiniroleThe metabolism of Ropinirole can be decreased when combined with Bortezomib.
RopivacaineThe metabolism of Ropivacaine can be decreased when combined with Bortezomib.
SaquinavirThe serum concentration of Bortezomib can be increased when it is combined with Saquinavir.
SertralineThe metabolism of Bortezomib can be decreased when combined with Sertraline.
SiltuximabThe serum concentration of Bortezomib can be decreased when it is combined with Siltuximab.
St. John's WortThe serum concentration of Bortezomib can be decreased when it is combined with St. John's Wort.
StiripentolThe metabolism of Stiripentol can be decreased when combined with Bortezomib.
TasimelteonThe metabolism of Tasimelteon can be decreased when combined with Bortezomib.
TelaprevirThe serum concentration of Bortezomib can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Bortezomib can be increased when it is combined with Telithromycin.
TeriflunomideThe serum concentration of Bortezomib can be decreased when it is combined with Teriflunomide.
TheophyllineThe metabolism of Theophylline can be decreased when combined with Bortezomib.
ThiothixeneThe metabolism of Thiothixene can be decreased when combined with Bortezomib.
TiclopidineThe metabolism of Bortezomib can be decreased when combined with Ticlopidine.
TizanidineThe serum concentration of Tizanidine can be increased when it is combined with Bortezomib.
TocilizumabThe serum concentration of Bortezomib can be decreased when it is combined with Tocilizumab.
TranylcypromineThe metabolism of Bortezomib can be decreased when combined with Tranylcypromine.
TrifluoperazineThe metabolism of Trifluoperazine can be decreased when combined with Bortezomib.
TrimipramineThe metabolism of Trimipramine can be decreased when combined with Bortezomib.
VemurafenibThe serum concentration of Bortezomib can be increased when it is combined with Vemurafenib.
Vitamin CThe therapeutic efficacy of Bortezomib can be decreased when used in combination with Vitamin C.
VoriconazoleThe serum concentration of Bortezomib can be increased when it is combined with Voriconazole.
Food Interactions
  • Citrus fruits - Patients should avoid taking extra vitamin C (ascorbic acid) supplements and vitamin C-containing multi-vitamins during their bortezomib therapy. Ascorbic Acid may diminish the therapeutic effect of Bortezomib.
  • Green Tea - Green Tea may diminish the antineoplastic effect of Bortezomib. Avoid concurrent use of green tea extract and other green tea products during treatment with bortezomib.

Targets

1. 26S proteasome non-ATPase regulatory subunit 2

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
26S proteasome non-ATPase regulatory subunit 2 Q13200 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. von Schwarzenberg K, Held SA, Schaub A, Brauer KM, Bringmann A, Brossart P: Proteasome inhibition overcomes the resistance of renal cell carcinoma cells against the PPARgamma ligand troglitazone. Cell Mol Life Sci. 2009 Apr;66(7):1295-308. Pubmed
  4. Marchi E, Paoluzzi L, Scotto L, Seshan VE, Zain JM, Zinzani PL, O’Connor OA: Pralatrexate is synergistic with the proteasome inhibitor bortezomib in in vitro and in vivo models of T-cell lymphoid malignancies. Clin Cancer Res. 2010 Jul 15;16(14):3648-58. Epub 2010 May 25. Pubmed
  5. Saeki Y, Fukunaga K, Tanaka K: [Proteasome inhibitors]. Nippon Rinsho. 2010 Oct;68(10):1818-22. Pubmed

2. 26S proteasome non-ATPase regulatory subunit 1

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
26S proteasome non-ATPase regulatory subunit 1 Q99460 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Saeki Y, Fukunaga K, Tanaka K: [Proteasome inhibitors]. Nippon Rinsho. 2010 Oct;68(10):1818-22. Pubmed

3. Proteasome subunit beta type-1

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Proteasome subunit beta type-1 P20618 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Saeki Y, Fukunaga K, Tanaka K: [Proteasome inhibitors]. Nippon Rinsho. 2010 Oct;68(10):1818-22. Pubmed
  4. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

4. Proteasome subunit beta type-5

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Proteasome subunit beta type-5 P28074 Details

References:

  1. Politou M, Karadimitris A, Terpos E, Kotsianidis I, Apperley JF, Rahemtulla A: No evidence of mutations of the PSMB5 (beta-5 subunit of proteasome) in a case of myeloma with clinical resistance to Bortezomib. Leuk Res. 2006 Feb;30(2):240-1. Epub 2005 Aug 2. Pubmed
  2. Saeki Y, Fukunaga K, Tanaka K: [Proteasome inhibitors]. Nippon Rinsho. 2010 Oct;68(10):1818-22. Pubmed
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

5. Proteasome subunit beta type-2

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Proteasome subunit beta type-2 P49721 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Saeki Y, Fukunaga K, Tanaka K: [Proteasome inhibitors]. Nippon Rinsho. 2010 Oct;68(10):1818-22. Pubmed
  4. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

6. Proteasome subunit alpha type-1

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Proteasome subunit alpha type-1 P25786 Details

References:

  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

7. Proteasome subunit alpha type-2

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Proteasome subunit alpha type-2 P25787 Details

References:

  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

8. Proteasome subunit alpha type-3

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Proteasome subunit alpha type-3 P25788 Details

References:

  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

9. Proteasome subunit alpha type-4

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Proteasome subunit alpha type-4 P25789 Details

References:

  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

10. Proteasome subunit alpha type-5

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Proteasome subunit alpha type-5 P28066 Details

References:

  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

11. Proteasome subunit alpha type-6

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Proteasome subunit alpha type-6 P60900 Details

References:

  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

12. Proteasome subunit alpha type-7

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Proteasome subunit alpha type-7 O14818 Details

References:

  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

13. Proteasome subunit beta type-3

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Proteasome subunit beta type-3 P49720 Details

References:

  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

14. Proteasome subunit beta type-4

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Proteasome subunit beta type-4 P28070 Details

References:

  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

15. Proteasome subunit beta type-6

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Proteasome subunit beta type-6 P28072 Details

References:

  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

16. Proteasome subunit beta type-7

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Proteasome subunit beta type-7 Q99436 Details

References:

  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  3. Lexicomp.

2. Cytochrome P450 2C19

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  3. Lexicomp

3. Cytochrome P450 2D6

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  3. Lexicomp.

4. Cytochrome P450 1A2

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  3. Lexicomp.

5. Cytochrome P450 2C9

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Prostaglandin G/H synthase 1

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Prostaglandin G/H synthase 1 P23219 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

7. Cytochrome P450 1A1

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A1 P04798 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

8. Cytochrome P450 2C8

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Transporters

1. High affinity copper uptake protein 1

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
High affinity copper uptake protein 1 O15431 Details

References:

  1. Jandial DD, Farshchi-Heydari S, Larson CA, Elliott GI, Wrasidlo WJ, Howell SB: Enhanced delivery of cisplatin to intraperitoneal ovarian carcinomas mediated by the effects of bortezomib on the human copper transporter 1. Clin Cancer Res. 2009 Jan 15;15(2):553-60. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on November 14, 2015 11:36