Bortezomib

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H25BN4O4
Molecular Weight	384.237
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)C[C@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)C2=NC=CN=C2)B(O)O

InChI

InChIKey=GXJABQQUPOEUTA-RDJZCZTQSA-N

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

HIDE SMILES / InChI

Molecular Formula	C19H25BN4O4
Molecular Weight	384.237
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021602s015lbl.pdf
Curator's Comment: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/11854543 http://www.drugbank.ca/drugs/DB00188 https://www.drugs.com/mtm/bortezomib.html https://en.wikipedia.org/wiki/Bortezomib

Bortezomib is the therapeutic proteasome inhibitor. First, which is tested in humans. The boron atom in bortezomib binds the catalytic site of the 26S proteasome with high affinity and specificity. Bortezomib is approved in the U.S. for treating relapsed multiple myeloma and mantle cell lymphoma. 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. Most commonly reported adverse reactions (incidence ≥30%) in clinical studies include asthenic conditions, diarrhea, nausea, constipation, peripheral neuropathy, vomiting, pyrexia, thrombocytopenia, psychiatric disorders, anorexia and decreased appetite, neutropenia, neuralgia, leukopenia and anemia. Co-administration of ketoconazole, a potent CYP3A inhibitor, increased the exposure of bortezomib. Co-administration of melphalan-prednisone increased the exposure of bortezomib. However, this increase is unlikely to be clinically relevant.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
26S proteosome 7 Target ID: CHEMBL2364701 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021602s015lbl.pdf	Inhibitor 8504		0.6 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Multiple myeloma 159 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021602s015lbl.pdf	Primary		Approved 8583	VELCADE Approved Use VELCADE is a proteasome inhibitor indicated for: treatment of patients with multiple myeloma (1.1) treatment of patients with mantle cell lymphoma (1.2) 1.1 Multiple Myeloma VELCADE® (bortezomib) is indicated for the treatment of patients with multiple myeloma. 1.2 Mantle Cell Lymphoma VELCADE is indicated for the treatment of patients with mantle cell lymphoma. Launch Date 2003
Mantle cell lymphoma 24 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021602s015lbl.pdf	Primary		Approved 8583	VELCADE Approved Use VELCADE is a proteasome inhibitor indicated for: treatment of patients with multiple myeloma (1.1) treatment of patients with mantle cell lymphoma (1.2) 1.1 Multiple Myeloma VELCADE® (bortezomib) is indicated for the treatment of patients with multiple myeloma. 1.2 Mantle Cell Lymphoma VELCADE is indicated for the treatment of patients with mantle cell lymphoma. Launch Date 2003

C_max

Value	Dose	Analyte	Population
127.02 ng/mL CLINICAL TRIAL https://clinicaltrials.gov/ct2/show/NCT01801436	1.3 mg/m² 2 times / week multiple, intravenous dose: 1.3 mg/m² route of administration: intravenous experiment type: MULTIPLE co-administered:	BORTEZOMIB plasma	Homo sapiens population: unhealthy age: ADULT sex: FEMALE / MALE food status: UNKNOWN
106.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20306195	1 mg/m² 2 times / week multiple, intravenous dose: 1 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	BORTEZOMIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
112 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021602s040lbl.pdf	1.3 mg/m² single, intravenous dose: 1.3 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	BORTEZOMIB plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
349.62 ng*h/mL CLINICAL TRIAL https://clinicaltrials.gov/ct2/show/NCT01801436	1.3 mg/m² 2 times / week multiple, intravenous dose: 1.3 mg/m² route of administration: intravenous experiment type: MULTIPLE co-administered:		BORTEZOMIB plasma	Homo sapiens population: unhealthy age: ADULT sex: FEMALE / MALE food status: UNKNOWN
82.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20306195	1 mg/m² 2 times / week multiple, intravenous dose: 1 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		BORTEZOMIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
51.55 h CLINICAL TRIAL https://clinicaltrials.gov/ct2/show/NCT01801436	1.3 mg/m² 2 times / week multiple, intravenous dose: 1.3 mg/m² route of administration: intravenous experiment type: MULTIPLE co-administered:		BORTEZOMIB plasma	Homo sapiens population: unhealthy age: ADULT sex: FEMALE / MALE food status: UNKNOWN
78.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20306195	1 mg/m² 2 times / week multiple, intravenous dose: 1 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		BORTEZOMIB blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
17% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021602s040lbl.pdf	1.3 mg/m² single, intravenous dose: 1.3 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		BORTEZOMIB plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
1.9 mg/m2 2 times / week steady, intravenous Highest studied dose Dose: 1.9 mg/m2, 2 times / week Route: intravenous Route: steady Dose: 1.9 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/20213332	unhealthy, 52 years (range: 26–85 years) Health Status: unhealthy Age Group: 52 years (range: 26–85 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/20213332	DLT: Thrombocytopenia, Sensory neuropathy... Other AEs: Diarrhea, Hypotension... Dose limiting toxicities: Thrombocytopenia (grade 3, 1 patient) Sensory neuropathy (grade 3, 1 patient) Fatigue (grade 3, 1 patient) Other AEs: Diarrhea (grade 3-4, 1 patient) Hypotension (grade 3-4, 1 patient) Hypoxia (grade 3-4, 1 patient) Infection (grade 3-4, 1 patient) Acidosis (grade 3-4) CPK increased (grade 3-4) Blood bicarbonate low (grade 3-4) Hypokalemia (grade 3-4) Alanine aminotransferase increase (grade 3-4) Sources: https://pubmed.ncbi.nlm.nih.gov/20213332
1.7 mg/m2 2 times / week steady, intravenous MTD Dose: 1.7 mg/m2, 2 times / week Route: intravenous Route: steady Dose: 1.7 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/20213332	unhealthy, 52 years (range: 26–85 years) Health Status: unhealthy Age Group: 52 years (range: 26–85 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/20213332	Other AEs: Thrombocytopenia, Sensory neuropathy... Other AEs: Thrombocytopenia (all grades, 5 patients) Sensory neuropathy (grade 3, 3 patients) Abdominal pain (grade 3, 1 patient) Constipation (grade 3, 1 patient) Depressed level of consciousness (grade 3, 1 patient) Fatigue (grade 3, 1 patient) Headache (grade 3, 1 patient) Pain (grade 3, 1 patient) Hypokalemia (grade 3, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/20213332
1.3 mg/m2 2 times / week steady, intravenous Recommended Dose: 1.3 mg/m2, 2 times / week Route: intravenous Route: steady Dose: 1.3 mg/m2, 2 times / week Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205004s000lbl.pdf	unhealthy, 71 years (range: 48 - 91 years) Health Status: unhealthy Age Group: 71 years (range: 48 - 91 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205004s000lbl.pdf	Other AEs: Thrombocytopenia, Thrombocytopenia... Other AEs: Thrombocytopenia (grade 3, 18%) Thrombocytopenia (grade 4-5, 17%) Neutropenia (grade 3, 30%) Neutropenia (grade 4-5, 10%) Anemia (grade 3, 12%) Anemia (grade 4-5, 1%) Leukopenia (grade 3, 19%) Leukopenia (grade 4-5, 2%) Lymphopenia (grade 3, 14%) Lymphopenia (grade 4-5, 5%) Nausea (grade 3, 3%) Diarrhea (grade 3, 6%) Diarrhea (grade 4-5, 1%) Vomiting (grade 3, 4%) Constipation (grade 3, 1%) Abdominal pain upper (grade 3, <1%) Peripheral neuropathy (grade 3, 12%) Peripheral neuropathy (grade 4-5, 1%) Neuralgia (grade 3, 8%) Neuralgia (grade 4-5, 1%) Paresthesia (grade 3, 2%) Fatigue (grade 3, 6%) Fatigue (grade 4-5, 1%) Asthenia (grade 3, 5%) Pyrexia (grade 3, 1%) Herpes zoster (grade 3, 3%) Anorexia (grade 3, 2%) Rash (grade 3, 1%) Insomnia (grade 3, < 1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205004s000lbl.pdf
1.3 mg/m2 2 times / week steady, intravenous Recommended Dose: 1.3 mg/m2, 2 times / week Route: intravenous Route: steady Dose: 1.3 mg/m2, 2 times / week Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205004s000lbl.pdf	unhealthy Health Status: unhealthy Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205004s000lbl.pdf	Disc. AE: Peripheral neuropathy, Cardiogenic shock... Other AEs: Diarrhea, Dehydration... AEs leading to discontinuation/dose reduction: Peripheral neuropathy (8%) Cardiogenic shock (grade 5, 1 patient) Respiratory insufficiency (grade 5, 1 patient) Congestive heart failure (grade 5, 1 patient) Cardiac arrest (grade 5, 1 patient) Fatigue (2%) Thrombocytopenia (2%) Diarrhea (2%) Other AEs: Diarrhea (serious, 3%) Dehydration (serious, 2%) Herpes zoster (serious, 2%) Pyrexia (serious, 2%) Nausea (serious, 2%) Vomiting (serious, 2%) Dyspnea (serious, 2%) Thrombocytopenia (serious, 2%) Constipation (grade 3, 2%) Anorexia (grade 3, 2%) Paresthesia (grade 3, 2%) Anaemia NOS (grade 3, 6%) Anaemia NOS (grade 4, <1%) Headache (grade 3, <1%) Neutropenia (grade 3, 11%) Neutropenia (grade 4, 2%) Rash NOS (grade 3, <1%) Abdominal pain (grade 3, 2%) Weakness (grade 3, 3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205004s000lbl.pdf
1.3 mg/m2 2 times / week steady, intravenous Recommended Dose: 1.3 mg/m2, 2 times / week Route: intravenous Route: steady Dose: 1.3 mg/m2, 2 times / week Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205004s000lbl.pdf	unhealthy Health Status: unhealthy Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205004s000lbl.pdf	Disc. AE: Hypotension, Pyrexia... AEs leading to discontinuation/dose reduction: Hypotension (1%) Pyrexia (< 1%) Weakness (< 1%) Asthenia (< 1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205004s000lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252 inducer 1087	substrate 1193 inhibitor 2438	substrate 1388 inhibitor 2507	activator 14

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 OATP1B1 1079 OATP1B3 961 BCRP 910 CYP2C19 2057	CYP1A2 1197 CYP2C19 1119 P-gp 2052	CYP1A2 832

Drug as perpetrator

Target	Modality	Activity
BCRP 985	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23589314/ Page: -	no
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021602s015lbl.pdf Page: -	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021602s015lbl.pdf Page: -	no
OATP1B1 1095	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29107984/ Page: -	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=11 Page: 11.0	weak [IC50 >30 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=11 Page: 11.0	weak [IC50 >30 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=11 Page: 11.0	weak [IC50 >30 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=11 Page: 11.0	weak [IC50 >30 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021602s015lbl.pdf Page: -	yes [IC50 18 uM]
OATP1B3 970	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/29107984/ Page: -	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=2 Page: 2.0	major	yes (co-administration study) Comment: Co-administration of ketoconazole, a potent CYP3A inhibitor, increased theexposure of bortezomib. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=2 Page: 2.0
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=12 Page: 12.0	no
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=9 Page: 9.0	yes
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=9 Page: 9.0	yes
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=9 Page: 9.0	yes
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=9 Page: 9.0	yes	no (co-administration study) Comment: Co-administration of omeprazole, a potent inhibitor of CYP2C19, had noeffect on the exposure of bortezomib. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=9 Page: 9.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	activator 14 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122396/ Page: -

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:52717	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:52717
eMolecules	29934400	https://www.emolecules.com/cgi-bin/more?vid=29934400
MolPort	MolPort-003-845-298	https://www.molport.com/shop/molecule-link/MolPort-003-845-298
Selleck Chemicals	Bortezomib	http://www.selleckchem.com/products/Bortezomib.html
ZINC	ZINC000169746649	http://zinc15.docking.org/substances/ZINC000169746649

PubMed

Title	Date	PubMed
Synergistic interaction of the histone deacetylase inhibitor SAHA with the proteasome inhibitor bortezomib in mantle cell lymphoma.	2008-02	18005386
CHOP transcription factor mediates IL-8 signaling in cystic fibrosis bronchial epithelial cells.	2008-02	17709599
Bortezomib induces caspase-dependent apoptosis in Hodgkin lymphoma cell lines and is associated with reduced c-FLIP expression: a gene expression profiling study with implications for potential combination therapies.	2008-02	17659339
Bortezomib is synergistic with rituximab and cyclophosphamide in inducing apoptosis of mantle cell lymphoma cells in vitro and in vivo.	2008-01	17898787
PS-341 (Bortezomib) inhibits proliferation and induces apoptosis of megakaryoblastic MO7-e cells.	2008-01	17629554
A novel bioluminescent mouse model and effective therapy for adult T-cell leukemia/lymphoma.	2007-12-15	18089816
Bortezomib induces apoptosis in T-cell prolymphocytic leukemia (T-PLL).	2007-11	17990182
Novel therapies in myeloma.	2007-11	17898564
Induction of heme oxygenase-1 by cobalt protoporphyrin enhances the antitumour effect of bortezomib in adult T-cell leukaemia cells.	2007-10-22	17895889
The proteasome inhibitor bortezomib induces apoptosis in human retinoblastoma cell lines in vitro.	2007-10	17898295
Bortezomib-associated cutaneous vasculitis.	2007-10	17635511
Bortezomib sensitizes non-Hodgkin's lymphoma cells to apoptosis induced by antibodies to tumor necrosis factor related apoptosis-inducing ligand (TRAIL) receptors TRAIL-R1 and TRAIL-R2.	2007-09-15	17875785
Topoisomerase IIbeta mediated DNA double-strand breaks: implications in doxorubicin cardiotoxicity and prevention by dexrazoxane.	2007-09-15	17875725
Bortezomib induces apoptosis of Epstein-Barr virus (EBV)-transformed B cells and prolongs survival of mice inoculated with EBV-transformed B cells.	2007-09	17626072
Predictive value of alkaline phosphatase for response and time to progression in bortezomib-treated multiple myeloma patients.	2007-09	17546639
TRAIL therapy in non-small cell lung cancer cells: sensitization to death receptor-mediated apoptosis by proteasome inhibitor bortezomib.	2007-07	17620439
Arsenic trioxide and proteasome inhibitor bortezomib synergistically induce apoptosis in leukemic cells: the role of protein kinase Cdelta.	2007-07	17495969
SAHA induces apoptosis in hepatoma cells and synergistically interacts with the proteasome inhibitor Bortezomib.	2007-07	17351739
The proteasome inhibitor PS-341 (bortezomib) up-regulates DR5 expression leading to induction of apoptosis and enhancement of TRAIL-induced apoptosis despite up-regulation of c-FLIP and survivin expression in human NSCLC cells.	2007-05-15	17510429
Capsaicin is a novel blocker of constitutive and interleukin-6-inducible STAT3 activation.	2007-05-15	17505005
Proteasome inhibitors synergize with tumor necrosis factor-related apoptosis-induced ligand to induce anaplastic thyroid carcinoma cell death.	2007-05	17327374
Complete remission and early relapse of refractory plasma cell leukemia after bortezomib induction and consolidation by HLA-mismatched unrelated allogeneic stem cell transplantation.	2007-04	17396042
Bortezomib-mediated 26S proteasome inhibition causes cell-cycle arrest and induces apoptosis in CD-30+ anaplastic large cell lymphoma.	2007-04	17268529
Quantitative sensory findings in patients with bortezomib-induced pain.	2007-04	17175202
Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-kappaB-regulated antiapoptotic and cell survival gene products in human multiple myeloma cells.	2007-03-15	17164350
TRAIL/bortezomib cotreatment is potentially hepatotoxic but induces cancer-specific apoptosis within a therapeutic window.	2007-03	17326159
Bortezomib-induced peripheral neurotoxicity: a neurophysiological and pathological study in the rat.	2007-03	17214983
A phase I and pharmacologic study of sequences of the proteasome inhibitor, bortezomib (PS-341, Velcade), in combination with paclitaxel and carboplatin in patients with advanced malignancies.	2007-02	16763792
[Salvage therapy with proteasome inhibitor bortezomib for relapsed and refractory multiple myeloma].	2006-12	17204182
Combination therapy with IFN-alpha plus bortezomib induces apoptosis and inhibits angiogenesis in human bladder cancer cells.	2006-12	17172406
Bortezomib (PS-341, Velcade) increases the efficacy of trastuzumab (Herceptin) in HER-2-positive breast cancer cells in a synergistic manner.	2006-12	17148762
Gallium-induced cell death in lymphoma: role of transferrin receptor cycling, involvement of Bax and the mitochondria, and effects of proteasome inhibition.	2006-11	17121930
Proteasome inhibitor PS-341 induces apoptosis in cisplatin-resistant squamous cell carcinoma cells by induction of Noxa.	2006-10-20	16928686
Histone deacetylase inhibitor trichostatin A and proteasome inhibitor PS-341 synergistically induce apoptosis in pancreatic cancer cells.	2006-10-06	16904634
Adaphostin and bortezomib induce oxidative injury and apoptosis in imatinib mesylate-resistant hematopoietic cells expressing mutant forms of Bcr/Abl.	2006-10	16481037
[Apoptosis of myeloid leukemia cell line HL60 induced by Bortezomib, a proteasome inhibitor].	2006-09-12	17156654
Phase II study of single-agent bortezomib for the treatment of patients with fludarabine-refractory B-cell chronic lymphocytic leukemia.	2006-09-01	16832816
Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways.	2006-09	16985072
Bortezomib inhibits docetaxel-induced apoptosis via a p21-dependent mechanism in human prostate cancer cells.	2006-08	16928825
Bortezomib and depsipeptide sensitize tumors to tumor necrosis factor-related apoptosis-inducing ligand: a novel method to potentiate natural killer cell tumor cytotoxicity.	2006-07-15	16849582
Activation of sterile20-like kinase 1 in proteasome inhibitor bortezomib-induced apoptosis in oncogenic K-ras-transformed cells.	2006-06-15	16778179
Bortezomib-dexamethasone combination in a patient with refractory multiple myeloma and impaired renal function.	2006-06	16860177
Inhibition of p38alpha MAPK enhances proteasome inhibitor-induced apoptosis of myeloma cells by modulating Hsp27, Bcl-X(L), Mcl-1 and p53 levels in vitro and inhibits tumor growth in vivo.	2006-06	16617327
Severe reversible cardiac failure after bortezomib treatment combined with chemotherapy in a non-small cell lung cancer patient: a case report.	2006-05-11	16689991
The combination of the proteasome inhibitor bortezomib and the bcl-2 antisense molecule oblimersen sensitizes human B-cell lymphomas to cyclophosphamide.	2006-05-01	16675587
PS-341 (bortezomib) induces lysosomal cathepsin B release and a caspase-2-dependent mitochondrial permeabilization and apoptosis in human pancreatic cancer cells.	2006-04-28	16446371
Aggresome disruption: a novel strategy to enhance bortezomib-induced apoptosis in pancreatic cancer cells.	2006-04-01	16585204
Modulation of uridine phosphorylase gene expression by tumor necrosis factor-alpha enhances the antiproliferative activity of the capecitabine intermediate 5'-deoxy-5-fluorouridine in breast cancer cells.	2006-04	16397116
Crystal structure of the boronic acid-based proteasome inhibitor bortezomib in complex with the yeast 20S proteasome.	2006-03	16531229
New treatments for multiple myeloma.	2005-12	16506632

Patents

Sample Use Guides

In Vivo Use Guide

1.3 mg/m2 administered as a 3 to 5 second bolus.

Route of Administration: Intravenous

In Vitro Use Guide

Fifty % growth inhibition (IC50) in U266, IM-9, and Hs Sultan (multiple myeloma) cells was noted at concentrations of 0.003, 0.006, or 0.02 × 10−6 M, respectively.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:11:16 GMT 2025` Edited by `admin` on `Mon Mar 31 18:11:16 GMT 2025`
Record UNII	69G8BD63PP
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

BORTEZOMIB ACCORD

Preferred Name

English

Bortezomib

Official Name

English

BORTEZOMIB [USAN]

Common Name

English

PS-341

Code

English

BORTEZOMIB [VANDF]

Common Name

English

Bortezomib [WHO-DD]

Common Name

English

BORTEZOMIB [ORANGE BOOK]

Common Name

English

BORTEZOMIB [MART.]

Common Name

English

NSC-681239

Code

English

LDP-341

Code

English

BORTEZOMIB [HSDB]

Common Name

English

BORTEZOMIB [MI]

Common Name

English

VELCADE

Brand Name

English

BORONIC ACID, ((1R)-3-METHYL-1-(((2S)-1-OXO-3-PHENYL-2-((PYRAZINYLCARBONYL)AMINO)PROPYL)AMINO)BUTYL)-

Common Name

English

[(1R)-3-Methyl-1-[[(2S)-3-phenyl-2-[(pyrazinylcarbonyl)amino]propanoyl]amino]butyl]boronic acid

Systematic Name

English

N-((1S)-1-BENZYL-2-(((1R)-1-(DIHYDROXYBORANYL)-3-METHYLBUTYL)AMINO)-2-OXOETHYL)PYRAZINECARBOXAMIDE

Systematic Name

English

BORTEZOMIB HYDRATE [JAN]

Common Name

English

BORTEZOMIB [JAN]

Common Name

English

bortezomib [INN]

Common Name

English

BORTEZOMIB [EMA EPAR]

Common Name

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

VELCADE (AUTHORIZED: MULTIPLE MYELOMA)