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
Development of the proteasome inhibitor Velcade (Bortezomib).	2004	15199612
Treatment of human chronic lymphocytic leukemia cells with the proteasome inhibitor bortezomib promotes apoptosis.	2004 Aug	15203282
Synergistic effect of histone deacetylase inhibitors FK228 and m-carboxycinnamic acid bis-hydroxamide with proteasome inhibitors PSI and PS-341 against gastrointestinal adenocarcinoma cells.	2004 Jun 1	15173094
Proteasome inhibition sensitizes non-small cell lung cancer to histone deacetylase inhibitor-induced apoptosis through the generation of reactive oxygen species.	2004 Nov	15514602
Proteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cells.	2004 Nov	15509775
Tumour lysis syndrome in multiple myeloma after bortezomib (VELCADE) administration.	2004 Oct	15449188
Antitumor effects of bortezomib (PS-341) on primary effusion lymphomas.	2004 Oct	15343345
Novel biological therapies for the treatment of multiple myeloma.	2005	16026741
Reduction in BCL-2 levels by 26S proteasome inhibition with bortezomib is associated with induction of apoptosis in small cell lung cancer.	2005 Aug	16022909
Perspectives for combination therapy to overcome drug-resistant multiple myeloma.	2005 Aug	16019253
A phase II trial with pharmacodynamic endpoints of the proteasome inhibitor bortezomib in patients with metastatic colorectal cancer.	2005 Aug 1	16061869
New treatments for multiple myeloma.	2005 Dec	16506632
Bortezomib, a novel proteasome inhibitor, in the treatment of hematologic malignancies.	2005 Dec	16298074
Sustained remission including marked regression of a paravertebral plasmacytoma in a patient with heavily pretreated, relapsed multiple myeloma after treatment with bortezomib.	2005 Dec	15964068
Bortezomib sensitizes pancreatic cancer cells to endoplasmic reticulum stress-mediated apoptosis.	2005 Dec 15	16357177
The combination of the farnesyl transferase inhibitor lonafarnib and the proteasome inhibitor bortezomib induces synergistic apoptosis in human myeloma cells that is associated with down-regulation of p-AKT.	2005 Dec 15	16118318
Bortezomib-induced severe hepatitis in multiple myeloma: a case report.	2005 Feb 28	15738379
Efficacy and mechanism of action of the proteasome inhibitor PS-341 in T-cell lymphomas and HTLV-I associated adult T-cell leukemia/lymphoma.	2005 Jan 13	15543232
Differential regulation of noxa in normal melanocytes and melanoma cells by proteasome inhibition: therapeutic implications.	2005 Jul 15	16024631
Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma.	2005 Jun	15953004
PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma.	2005 Jun	15953001
Human metabolism of the proteasome inhibitor bortezomib: identification of circulating metabolites.	2005 Jun	15764713
Bortezomib abolishes tumor necrosis factor-related apoptosis-inducing ligand resistance via a p21-dependent mechanism in human bladder and prostate cancer cells.	2005 Jun 1	15930312
Serum amyloid A-luciferase transgenic mice: response to sepsis, acute arthritis, and contact hypersensitivity and the effects of proteasome inhibition.	2005 Jun 15	15944321
NF-kappaB and not the MAPK signaling pathway regulates GADD45beta expression during acute inflammation.	2005 Jun 3	15797874
Predominant Bcl-XL knockdown disables antiapoptotic mechanisms: tumor necrosis factor-related apoptosis-inducing ligand-based triple chemotherapy overcomes chemoresistance in pancreatic cancer cells in vitro.	2005 Mar 15	15781649
Severe irreversible bilateral hearing loss after bortezomib (VELCADE) therapy in a multiple myeloma (MM) patient.	2005 May	15772697
PS-341 (bortezomib) induces lysosomal cathepsin B release and a caspase-2-dependent mitochondrial permeabilization and apoptosis in human pancreatic cancer cells.	2006 Apr 28	16446371
Bortezomib inhibits docetaxel-induced apoptosis via a p21-dependent mechanism in human prostate cancer cells.	2006 Aug	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 Jul 15	16849582
Activation of sterile20-like kinase 1 in proteasome inhibitor bortezomib-induced apoptosis in oncogenic K-ras-transformed cells.	2006 Jun 15	16778179
Bortezomib induces selective depletion of alloreactive T lymphocytes and decreases the production of Th1 cytokines.	2006 May 1	16282346
Gallium-induced cell death in lymphoma: role of transferrin receptor cycling, involvement of Bax and the mitochondria, and effects of proteasome inhibition.	2006 Nov	17121930
Proteasome inhibitor PS-341 induces apoptosis in cisplatin-resistant squamous cell carcinoma cells by induction of Noxa.	2006 Oct 20	16928686
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 Sep	16985072
[Apoptosis of myeloid leukemia cell line HL60 induced by Bortezomib, a proteasome inhibitor].	2006 Sep 12	17156654
A novel bioluminescent mouse model and effective therapy for adult T-cell leukemia/lymphoma.	2007 Dec 15	18089816
SAHA induces apoptosis in hepatoma cells and synergistically interacts with the proteasome inhibitor Bortezomib.	2007 Jul	17351739
Bortezomib induces apoptosis in T-cell prolymphocytic leukemia (T-PLL).	2007 Nov	17990182
Novel therapies in myeloma.	2007 Nov	17898564
The proteasome inhibitor bortezomib induces apoptosis in human retinoblastoma cell lines in vitro.	2007 Oct	17898295
Bortezomib-associated cutaneous vasculitis.	2007 Oct	17635511
Induction of heme oxygenase-1 by cobalt protoporphyrin enhances the antitumour effect of bortezomib in adult T-cell leukaemia cells.	2007 Oct 22	17895889
Predictive value of alkaline phosphatase for response and time to progression in bortezomib-treated multiple myeloma patients.	2007 Sep	17546639
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 Sep 15	17875785
Topoisomerase IIbeta mediated DNA double-strand breaks: implications in doxorubicin cardiotoxicity and prevention by dexrazoxane.	2007 Sep 15	17875725
Synergistic interaction of the histone deacetylase inhibitor SAHA with the proteasome inhibitor bortezomib in mantle cell lymphoma.	2008 Feb	18005386
CHOP transcription factor mediates IL-8 signaling in cystic fibrosis bronchial epithelial cells.	2008 Feb	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 Feb	17659339
Bortezomib is synergistic with rituximab and cyclophosphamide in inducing apoptosis of mantle cell lymphoma cells in vitro and in vivo.	2008 Jan	17898787

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

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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)