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 8228		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 8360	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 1.052784E12
Mantle cell lymphoma 24 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021602s015lbl.pdf	Primary		Approved 8360	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 1.052784E12

C_max

Value	Dose	Analyte	Population
106.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20306195	1 mg/m² 1 times / 4 days multiple, oral dose: 1 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:	BORTEZOMIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
127.02 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01801436	1.3 mg/m^2 1 times / 4 day steady, intravenous dose: 1.3 mg/m^2 route of administration: intravenous experiment type: steady co-administered:	BORTEZOMIB plasma	Homo sapiens population: unhealthy age: sex: food status:
76.43 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01801436	1.3 mg/m^2 single, intravenous dose: 1.3 mg/m^2 route of administration: intravenous experiment type: single co-administered:	BORTEZOMIB plasma	Homo sapiens population: unhealthy age: sex: food status:

AUC

Value	Dose	Analyte	Population
82.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20306195	1 mg/m² 1 times / 4 days multiple, oral dose: 1 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:	BORTEZOMIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
190.39 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01801436	1.3 mg/m^2 1 times / 4 day steady, intravenous dose: 1.3 mg/m^2 route of administration: intravenous experiment type: steady co-administered:	BORTEZOMIB plasma	Homo sapiens population: unhealthy age: sex: food status:
51.86 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01801436	1.3 mg/m^2 single, intravenous dose: 1.3 mg/m^2 route of administration: intravenous experiment type: single co-administered:	BORTEZOMIB plasma	Homo sapiens population: unhealthy age: sex: food status:
106.99 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01801436	1.3 mg/m^2 single, intravenous dose: 1.3 mg/m^2 route of administration: intravenous experiment type: single co-administered:	BORTEZOMIB plasma	Homo sapiens population: unhealthy age: sex: food status:
349.62 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01801436	1.3 mg/m^2 1 times / 4 day steady, intravenous dose: 1.3 mg/m^2 route of administration: intravenous experiment type: steady co-administered:	BORTEZOMIB plasma	Homo sapiens population: unhealthy age: sex: food status:

T_1/2

Value	Dose	Analyte	Population
78.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20306195	1 mg/m² 1 times / 4 days multiple, oral dose: 1 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:	BORTEZOMIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.08 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01801436	1.3 mg/m^2 single, intravenous dose: 1.3 mg/m^2 route of administration: intravenous experiment type: single co-administered:	BORTEZOMIB plasma	Homo sapiens population: unhealthy age: sex: food status:
51.55 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01801436	1.3 mg/m^2 1 times / 4 day steady, intravenous dose: 1.3 mg/m^2 route of administration: intravenous experiment type: steady co-administered:	BORTEZOMIB plasma	Homo sapiens population: unhealthy age: sex: food status:

F_unbound

Value	Dose	Co-administered	Analyte	Population
17% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021602s040lbl.pdf			BORTEZOMIB plasma	Homo sapiens population: UNKNOWN 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) n = 33 Health Status: unhealthy Condition: recurrent malignant glioma Age Group: 52 years (range: 26–85 years) Sex: M+F Population Size: 33 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) n = 33 Health Status: unhealthy Condition: recurrent malignant glioma Age Group: 52 years (range: 26–85 years) Sex: M+F Population Size: 33 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 Co-administed with:: melphalan(9 mg/m2) prednisone(60 mg/m2) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205004s000lbl.pdf	unhealthy, 71 years (range: 48 - 91 years) n = 340 Health Status: unhealthy Condition: multiple myeloma Age Group: 71 years (range: 48 - 91 years) Sex: M+F Population Size: 340 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 n = 331 Health Status: unhealthy Condition: multiple myeloma \|mantle cell lymphoma Sex: M+F Population Size: 331 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
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 n = 331 Health Status: unhealthy Condition: relapsed multiple myeloma Sex: M+F Population Size: 331 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

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709 inhibitor 1579 inducer 768	substrate 1010 inhibitor 1752	substrate 1193 inhibitor 1837	activator 13

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1509 OATP1B1 781 OATP1B3 700 BCRP 691 CYP2C19 1463	CYP1A2 1032 CYP2C19 985 P-gp 1527	CYP1A2 689

Drug as perpetrator

Target	Modality	Activity
BCRP 765	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/23589314/ Page: -	no
CYP1A2 1673	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021602s015lbl.pdf Page: -	no
CYP3A4 1909	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021602s015lbl.pdf Page: -	no
OATP1B1 796	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29107984/ Page: -	no
CYP1A2 1673	inhibitor 3240 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 1803	inhibitor 3240 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 1875	inhibitor 3240 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 1909	inhibitor 3240 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 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021602s015lbl.pdf Page: -	yes [IC50 18 uM]
OATP1B3 709	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29107984/ Page: -	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1709	substrate 3326 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 1527	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=12 Page: 12.0	no
CYP1A2 1032	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=9 Page: 9.0	yes
CYP2C19 985	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=9 Page: 9.0	yes
CYP2D6 1193	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=9 Page: 9.0	yes
CYP2C9 1010	substrate 3326 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 1632	activator 13 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
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
eMolecules	29934400	https://www.emolecules.com/cgi-bin/more?vid=29934400

PubMed

Title	Date	PubMed

The proteasome inhibitor PS-341 overcomes TRAIL resistance in Bax and caspase 9-negative or Bcl-xL overexpressing cells.	2003 Aug 7	12902978
Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341.	2003 Feb 15	12393500
The proteasome inhibitor bortezomib interacts synergistically with histone deacetylase inhibitors to induce apoptosis in Bcr/Abl+ cells sensitive and resistant to STI571.	2003 Nov 15	12893773
[Treatment with a proteasome inhibitor, bortezomib, for thalidomide-resistant multiple myeloma].	2004 Feb	15045823
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
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
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
Sensitization of DNA damage-induced apoptosis by the proteasome inhibitor PS-341 is p53 dependent and involves target proteins 14-3-3sigma and survivin.	2005 Dec	16373703
Bortezomib, a novel proteasome inhibitor, in the treatment of hematologic malignancies.	2005 Dec	16298074
Bortezomib sensitizes pancreatic cancer cells to endoplasmic reticulum stress-mediated apoptosis.	2005 Dec 15	16357177
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
Sulindac enhances the proteasome inhibitor bortezomib-mediated oxidative stress and anticancer activity.	2005 Jul 15	16033843
New biological agents in the treatment of advanced non-small cell lung cancer.	2005 Jun	16052434
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
Intracellular protein degradation: from a vague idea, through the lysosome and the ubiquitin-proteasome system, and onto human diseases and drug targeting (Nobel lecture).	2005 Sep 19	16142822
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 (PS-341, Velcade) increases the efficacy of trastuzumab (Herceptin) in HER-2-positive breast cancer cells in a synergistic manner.	2006 Dec	17148762
Bortezomib-dexamethasone combination in a patient with refractory multiple myeloma and impaired renal function.	2006 Jun	16860177
Proteasome inhibitor PS-341 induces apoptosis in cisplatin-resistant squamous cell carcinoma cells by induction of Noxa.	2006 Oct 20	16928686
A novel bioluminescent mouse model and effective therapy for adult T-cell leukemia/lymphoma.	2007 Dec 15	18089816
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 Feb	16763792
Arsenic trioxide and proteasome inhibitor bortezomib synergistically induce apoptosis in leukemic cells: the role of protein kinase Cdelta.	2007 Jul	17495969
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 May 15	17510429
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
Predictive value of alkaline phosphatase for response and time to progression in bortezomib-treated multiple myeloma patients.	2007 Sep	17546639
Synergistic interaction of the histone deacetylase inhibitor SAHA with the proteasome inhibitor bortezomib in mantle cell lymphoma.	2008 Feb	18005386
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

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 `Wed Jul 05 23:20:09 UTC 2023` Edited by `admin` on `Wed Jul 05 23:20:09 UTC 2023`
Record UNII	69G8BD63PP
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BORTEZOMIB

Official Name

English

BORTEZOMIB [USAN]

Common Name

English

PS-341

Code

English

BORTEZOMIB [VANDF]

Common Name

English

BORTEZOMIB ACCORD

Brand 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)