BORTEZOMIB BORONIC ANHYDRIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C57H69B3N12O9
Molecular Weight	1098.666
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of BORTEZOMIB BORONIC ANHYDRIDE

Structure Search

SMILES

CC(C)C[C@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)C2=NC=CN=C2)B3OB(OB(O3)[C@H](CC(C)C)NC(=O)[C@H](CC4=CC=CC=C4)NC(=O)C5=NC=CN=C5)[C@H](CC(C)C)NC(=O)[C@H](CC6=CC=CC=C6)NC(=O)C7=NC=CN=C7

InChI

InChIKey=YVBHFXUJMLXLKP-INZJBPCBSA-N

InChI=1S/C57H69B3N12O9/c1-37(2)28-49(70-52(73)43(31-40-16-10-7-11-17-40)67-55(76)46-34-61-22-25-64-46)58-79-59(50(29-38(3)4)71-53(74)44(32-41-18-12-8-13-19-41)68-56(77)47-35-62-23-26-65-47)81-60(80-58)51(30-39(5)6)72-54(75)45(33-42-20-14-9-15-21-42)69-57(78)48-36-63-24-27-66-48/h7-27,34-39,43-45,49-51H,28-33H2,1-6H3,(H,67,76)(H,68,77)(H,69,78)(H,70,73)(H,71,74)(H,72,75)/t43-,44-,45-,49-,50-,51-/m0/s1

HIDE SMILES / InChI

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 8297		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 8429	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 8429	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
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 1737 inhibitor 1587 inducer 781	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852	activator 14

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 OATP1B1 788 OATP1B3 706 BCRP 699 CYP2C19 1478	CYP1A2 1054 CYP2C19 991 P-gp 1537	CYP1A2 701

Drug as perpetrator

Target	Modality	Activity
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23589314/ Page: -	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021602s015lbl.pdf Page: -	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021602s015lbl.pdf Page: -	no
OATP1B1 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29107984/ Page: -	no
CYP1A2 1692	inhibitor 3277 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 1819	inhibitor 3277 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 1891	inhibitor 3277 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 1925	inhibitor 3277 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 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021602s015lbl.pdf Page: -	yes [IC50 18 uM]
OATP1B3 715	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29107984/ Page: -	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1737	substrate 3367 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 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=12 Page: 12.0	no
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=9 Page: 9.0	yes
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=9 Page: 9.0	yes
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade_biopharmr_P1.pdf#page=9 Page: 9.0	yes
CYP2C9 1037	substrate 3367 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 1647	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
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
The proteasome as a target for cancer therapy.	2003 Dec 15	14695130
Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341.	2003 Feb 15	12393500
Blockade of Hsp27 overcomes Bortezomib/proteasome inhibitor PS-341 resistance in lymphoma cells.	2003 Oct 1	14559800
Effects of the proteasome inhibitor, bortezomib, on apoptosis in isolated lymphocytes obtained from patients with chronic lymphocytic leukemia.	2003 Oct 1	14555532
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
The proteasome inhibitor bortezomib enhances the activity of docetaxel in orthotopic human pancreatic tumor xenografts.	2004 Jan	14749476
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
Synergistic induction of oxidative injury and apoptosis in human multiple myeloma cells by the proteasome inhibitor bortezomib and histone deacetylase inhibitors.	2004 Jun 1	15173093
Simultaneous inhibition of hsp 90 and the proteasome promotes protein ubiquitination, causes endoplasmic reticulum-derived cytosolic vacuolization, and enhances antitumor activity.	2004 May	15141013
Phase I study of bortezomib in refractory or relapsed acute leukemias.	2004 May 15	15161691
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
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
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
Severe irreversible bilateral hearing loss after bortezomib (VELCADE) therapy in a multiple myeloma (MM) patient.	2005 May	15772697
Mammalian target of rapamycin inhibitors activate the AKT kinase in multiple myeloma cells by up-regulating the insulin-like growth factor receptor/insulin receptor substrate-1/phosphatidylinositol 3-kinase cascade.	2005 Oct	16227402
N-(4-hydroxyphenyl)retinamide inhibits invasion, suppresses osteoclastogenesis, and potentiates apoptosis through down-regulation of I(kappa)B(alpha) kinase and nuclear factor-kappaB-regulated gene products.	2005 Oct 15	16230421
Bortezomib (PS-341, Velcade) increases the efficacy of trastuzumab (Herceptin) in HER-2-positive breast cancer cells in a synergistic manner.	2006 Dec	17148762
Vitamin C inactivates the proteasome inhibitor PS-341 in human cancer cells.	2006 Jan 1	16397052
Bortezomib-dexamethasone combination in a patient with refractory multiple myeloma and impaired renal function.	2006 Jun	16860177
Activation of sterile20-like kinase 1 in proteasome inhibitor bortezomib-induced apoptosis in oncogenic K-ras-transformed cells.	2006 Jun 15	16778179
Severe reversible cardiac failure after bortezomib treatment combined with chemotherapy in a non-small cell lung cancer patient: a case report.	2006 May 11	16689991
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
Histone deacetylase inhibitor trichostatin A and proteasome inhibitor PS-341 synergistically induce apoptosis in pancreatic cancer cells.	2006 Oct 6	16904634
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
Phase II study of single-agent bortezomib for the treatment of patients with fludarabine-refractory B-cell chronic lymphocytic leukemia.	2006 Sep 1	16832816
A novel bioluminescent mouse model and effective therapy for adult T-cell leukemia/lymphoma.	2007 Dec 15	18089816
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
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.

Name

Type

Language

BORTEZOMIB BORONIC ANHYDRIDE

Common Name

English

2-PYRAZINECARBOXAMIDE, N,N',N''-(2,4,6-BOROXINTRIYLTRIS(((1R)-3-METHYLBUTYLIDENE)IMINO((1S)-2-OXO-1-(PHENYLMETHYL)-2,1-ETHANEDIYL)))TRIS-

Systematic Name

English

N,N',N''-((2S,2'S,2''S)-(((1R,1'R,1''R)-(1,3,5,2,4,6-TRIOXATRIBORINANE-2,4,6-TRIYL)TRIS(3-METHYLBUTANE-1,1-DIYL))TRIS(AZANEDIYL))TRIS(1-OXO-3-PHENYLPROPANE-1,2-DIYL))TRIS(PYRAZINE-2-CARBOXAMIDE)

Systematic Name

English

PYRAZINECARBOXAMIDE, N,N',N''-(2,4,6-BOROXINTRIYLTRIS(((1R)-3-METHYLBUTYLIDENE)IMINO((1S)-2-OXO-1-(PHENYLMETHYL)-2,1-ETHANEDIYL)))TRIS-

Systematic Name

English

Code System Code Type Description

PUBCHEM

60071654

Created by admin on Sat Dec 16 09:32:24 GMT 2023 , Edited by admin on Sat Dec 16 09:32:24 GMT 2023

PRIMARY

CAS

390800-88-1

Created by admin on Sat Dec 16 09:32:24 GMT 2023 , Edited by admin on Sat Dec 16 09:32:24 GMT 2023

PRIMARY

FDA UNII

264LX948L0

Created by admin on Sat Dec 16 09:32:24 GMT 2023 , Edited by admin on Sat Dec 16 09:32:24 GMT 2023

PRIMARY

ACTIVE MOIETY


					69G8BD63PP

BORTEZOMIB

SUBSTANCE RECORD


					264LX948L0

BORTEZOMIB BORONIC ANHYDRIDE

Details

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Approved Use

Launch Date

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator