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

Molecular Formula	C57H69B3N12O9
Molecular Weight	1098.666
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	6 / 6
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

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
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 Apr	16397116
Aggresome disruption: a novel strategy to enhance bortezomib-induced apoptosis in pancreatic cancer cells.	2006 Apr 1	16585204
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
[Salvage therapy with proteasome inhibitor bortezomib for relapsed and refractory multiple myeloma].	2006 Dec	17204182
Combination therapy with IFN-alpha plus bortezomib induces apoptosis and inhibits angiogenesis in human bladder cancer cells.	2006 Dec	17172406
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
The proteasome inhibitor bortezomib induces apoptosis in mantle-cell lymphoma through generation of ROS and Noxa activation independent of p53 status.	2006 Jan 1	16166592
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
Bortezomib-dexamethasone combination in a patient with refractory multiple myeloma and impaired renal function.	2006 Jun	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 Jun	16617327
Activation of sterile20-like kinase 1 in proteasome inhibitor bortezomib-induced apoptosis in oncogenic K-ras-transformed cells.	2006 Jun 15	16778179
Crystal structure of the boronic acid-based proteasome inhibitor bortezomib in complex with the yeast 20S proteasome.	2006 Mar	16531229
The combination of the proteasome inhibitor bortezomib and the bcl-2 antisense molecule oblimersen sensitizes human B-cell lymphomas to cyclophosphamide.	2006 May 1	16675587
Bortezomib induces selective depletion of alloreactive T lymphocytes and decreases the production of Th1 cytokines.	2006 May 1	16282346
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
Adaphostin and bortezomib induce oxidative injury and apoptosis in imatinib mesylate-resistant hematopoietic cells expressing mutant forms of Bcr/Abl.	2006 Oct	16481037
Proteasome inhibitor PS-341 induces apoptosis in cisplatin-resistant squamous cell carcinoma cells by induction of Noxa.	2006 Oct 20	16928686
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
[Apoptosis of myeloid leukemia cell line HL60 induced by Bortezomib, a proteasome inhibitor].	2006 Sep 12	17156654
Complete remission and early relapse of refractory plasma cell leukemia after bortezomib induction and consolidation by HLA-mismatched unrelated allogeneic stem cell transplantation.	2007 Apr	17396042
Bortezomib-mediated 26S proteasome inhibition causes cell-cycle arrest and induces apoptosis in CD-30+ anaplastic large cell lymphoma.	2007 Apr	17268529
Quantitative sensory findings in patients with bortezomib-induced pain.	2007 Apr	17175202
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
TRAIL therapy in non-small cell lung cancer cells: sensitization to death receptor-mediated apoptosis by proteasome inhibitor bortezomib.	2007 Jul	17620439
Arsenic trioxide and proteasome inhibitor bortezomib synergistically induce apoptosis in leukemic cells: the role of protein kinase Cdelta.	2007 Jul	17495969
SAHA induces apoptosis in hepatoma cells and synergistically interacts with the proteasome inhibitor Bortezomib.	2007 Jul	17351739
TRAIL/bortezomib cotreatment is potentially hepatotoxic but induces cancer-specific apoptosis within a therapeutic window.	2007 Mar	17326159
Bortezomib-induced peripheral neurotoxicity: a neurophysiological and pathological study in the rat.	2007 Mar	17214983
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 Mar 15	17164350
Proteasome inhibitors synergize with tumor necrosis factor-related apoptosis-induced ligand to induce anaplastic thyroid carcinoma cell death.	2007 May	17327374
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
The proteasome inhibitor bortezomib induces apoptosis in human retinoblastoma cell lines in vitro.	2007 Oct	17898295
Bortezomib-associated cutaneous vasculitis.	2007 Oct	17635511
Bortezomib induces apoptosis of Epstein-Barr virus (EBV)-transformed B cells and prolongs survival of mice inoculated with EBV-transformed B cells.	2007 Sep	17626072
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
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
PS-341 (Bortezomib) inhibits proliferation and induces apoptosis of megakaryoblastic MO7-e cells.	2008 Jan	17629554

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 `Thu Jul 06 15:01:36 UTC 2023` Edited by `admin` on `Thu Jul 06 15:01:36 UTC 2023`
Record UNII	264LX948L0
Record Status	`Validated (UNII)`
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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 Thu Jul 06 15:01:37 UTC 2023 , Edited by admin on Thu Jul 06 15:01:37 UTC 2023

PRIMARY

CAS

390800-88-1

Created by admin on Thu Jul 06 15:01:36 UTC 2023 , Edited by admin on Thu Jul 06 15:01:36 UTC 2023

PRIMARY

FDA UNII

264LX948L0

Created by admin on Thu Jul 06 15:01:36 UTC 2023 , Edited by admin on Thu Jul 06 15:01:36 UTC 2023

PRIMARY

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BORTEZOMIB

ACTIVE MOIETY

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