BORTEZOMIB D-MANNITOL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H35BN4O8
Molecular Weight	530.378
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]1(OB(O[C@]1([H])[C@H](O)CO)[C@H](CC(C)C)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)C3=NC=CN=C3)[C@H](O)CO

InChI

InChIKey=QDMRNLRJDHCHLB-DNNBANOASA-N

InChI=1S/C25H35BN4O8/c1-15(2)10-21(26-37-22(19(33)13-31)23(38-26)20(34)14-32)30-24(35)17(11-16-6-4-3-5-7-16)29-25(36)18-12-27-8-9-28-18/h3-9,12,15,17,19-23,31-34H,10-11,13-14H2,1-2H3,(H,29,36)(H,30,35)/t17-,19+,20+,21-,22+,23+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C25H35BN4O8
Molecular Weight	530.378
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
The proteasome as a target for cancer therapy.	2003 Dec 15	14695130
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
The bortezomib/proteasome inhibitor PS-341 and triterpenoid CDDO-Im induce synergistic anti-multiple myeloma (MM) activity and overcome bortezomib resistance.	2004 Apr 15	15070698
Treatment of human chronic lymphocytic leukemia cells with the proteasome inhibitor bortezomib promotes apoptosis.	2004 Aug	15203282
[Treatment with a proteasome inhibitor, bortezomib, for thalidomide-resistant multiple myeloma].	2004 Feb	15045823
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
Simultaneous inhibition of hsp 90 and the proteasome promotes protein ubiquitination, causes endoplasmic reticulum-derived cytosolic vacuolization, and enhances antitumor activity.	2004 May	15141013
Proteasome inhibition sensitizes non-small cell lung cancer to histone deacetylase inhibitor-induced apoptosis through the generation of reactive oxygen species.	2004 Nov	15514602
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
Activity of selective fully human agonistic antibodies to the TRAIL death receptors TRAIL-R1 and TRAIL-R2 in primary and cultured lymphoma cells: induction of apoptosis and enhancement of doxorubicin- and bortezomib-induced cell death.	2005 Aug	16098063
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
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
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
New biological agents in the treatment of advanced non-small cell lung cancer.	2005 Jun	16052434
PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma.	2005 Jun	15953001
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
NF-kappaB and not the MAPK signaling pathway regulates GADD45beta expression during acute inflammation.	2005 Jun 3	15797874
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
[Salvage therapy with proteasome inhibitor bortezomib for relapsed and refractory multiple myeloma].	2006 Dec	17204182
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
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
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
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
Quantitative sensory findings in patients with bortezomib-induced pain.	2007 Apr	17175202
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
TRAIL/bortezomib cotreatment is potentially hepatotoxic but induces cancer-specific apoptosis within a therapeutic window.	2007 Mar	17326159
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
Capsaicin is a novel blocker of constitutive and interleukin-6-inducible STAT3 activation.	2007 May 15	17505005
Bortezomib induces apoptosis in T-cell prolymphocytic leukemia (T-PLL).	2007 Nov	17990182
Novel therapies in myeloma.	2007 Nov	17898564
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
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
Synergistic interaction of the histone deacetylase inhibitor SAHA with the proteasome inhibitor bortezomib in mantle cell lymphoma.	2008 Feb	18005386
Bortezomib is synergistic with rituximab and cyclophosphamide in inducing apoptosis of mantle cell lymphoma cells in vitro and in vivo.	2008 Jan	17898787
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 19:34:48 UTC 2023` Edited by `admin` on `Thu Jul 06 19:34:48 UTC 2023`
Record UNII	P2AWN9VSQ6
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BORTEZOMIB D-MANNITOL

Common Name

English

BORTEZOMIB D-MANNITOL SYMMETRICAL ESTER

Common Name

English

BORTEZOMIB D-MANNITOL ESTER

Common Name

English

D-MANNITOL, CYCLIC 3,4-(B-((1R)-3-METHYL-1-(((2S)-1-OXO-3-PHENYL-2-((2-PYRAZINYLCARBONYL)AMINO)PROPYL)AMINO)BUTYL)BORONATE)

Common Name

English

BORTEZOMIB MANNITOL BORONIC ESTER

Common Name

English

Code System Code Type Description

SMS_ID

300000027876

Created by admin on Thu Jul 06 19:34:48 UTC 2023 , Edited by admin on Thu Jul 06 19:34:48 UTC 2023

PRIMARY

PUBCHEM

12990536

Created by admin on Thu Jul 06 19:34:48 UTC 2023 , Edited by admin on Thu Jul 06 19:34:48 UTC 2023

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FDA UNII

P2AWN9VSQ6

Created by admin on Thu Jul 06 19:34:48 UTC 2023 , Edited by admin on Thu Jul 06 19:34:48 UTC 2023

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CAS

444576-08-3

Created by admin on Thu Jul 06 19:34:48 UTC 2023 , Edited by admin on Thu Jul 06 19:34:48 UTC 2023

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Related Record Type Details


					69G8BD63PP

BORTEZOMIB

METABOLITE ACTIVE -> PRODRUG

Related Record Type Details


					69G8BD63PP

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