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Bortezomib

CAS No.
179324-69-7
Chemical Name:
Bortezomib
Synonyms
VELCADE;dpba;BortezoMib-D8;((R)-3-Methyl-1-((S)-3-phenyl-2-(pyrazine-2-carboxaMido)propanaMido)butyl)boronic acid;MLM341;Bozomi;CS-1886;Radiciol;BortezMib;ortezomib
CBNumber:
CB8721789
Molecular Formula:
C19H25BN4O4
Molecular Weight:
384.24
MDL Number:
MFCD09056737
MOL File:
179324-69-7.mol
Last updated:2023-09-18 19:31:40

Bortezomib Properties

Melting point 122-124°C
Density 1.214
RTECS ED7771666
storage temp. Inert atmosphere,Store in freezer, under -20°C
solubility Soluble in chloroform, dimethyl sulfoxide, ethanol and methanol.
pka 9.66±0.43(Predicted)
form solid
color White
Stability Hygroscopic and Moisture Sensitive
CAS DataBase Reference 179324-69-7(CAS DataBase Reference)
NCI Dictionary of Cancer Terms bortezomib; Velcade
FDA UNII 69G8BD63PP
NCI Drug Dictionary bortezomib
ATC code L01XG01

Pharmacokinetic data

Protein binding 82.9%
Excreted unchanged in urine Small amount
Volume of distribution 498-1,884 Litres/m2(L/kg)
Biological half-life 40-193 / Unknown

SAFETY

Risk and Safety Statements

Symbol(GHS)  GHS hazard pictogramsGHS hazard pictograms
GHS06,GHS08
Signal word  Danger
Hazard statements  H300-H310-H330-H372
Precautionary statements  P301+P310a-P304+P340-P320-P330-P405-P501a
Risk Statements  23/24/25-48/23/24/25
Safety Statements  9-27-36/37-45-60
HazardClass  6.1
HS Code  29339900
NFPA 704
0
4 0

Bortezomib price More Price(60)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich 5.04314 Bortezomib - CAS 179324-69-7 - Calbiochem Bortezomib, CAS 179324-69-7, is a cell-permeable, selective, slowly reversible inhibitor of 20S proteasome β5 ChTL/chymotrypsin- over β1 CL/caspase- and β2 TL/trypsin-like activity. 179324-69-7 5MG $129 2024-03-01 Buy
Alfa Aesar J60378 Bortezomib, 99% 179324-69-7 10mg $250 2024-03-01 Buy
Alfa Aesar J60378 Bortezomib, 99% 179324-69-7 25mg $437 2024-03-01 Buy
Cayman Chemical 10008822 Bortezomib ≥95% 179324-69-7 1mg $32 2024-03-01 Buy
Cayman Chemical 10008822 Bortezomib ≥95% 179324-69-7 5mg $70 2024-03-01 Buy
Product number Packaging Price Buy
5.04314 5MG $129 Buy
J60378 10mg $250 Buy
J60378 25mg $437 Buy
10008822 1mg $32 Buy
10008822 5mg $70 Buy

Bortezomib Chemical Properties,Uses,Production

Description

Bortezomib, a modified dipeptidyl boronic acid, is a therapeutic proteasome inhibitors used for the treatment of cancers. It is indicated for the treatment of relapsed multiple myeloma and mantle cell lymphoma. It is capable of inhibiting the mammalian 26S proteasome, which is important in regulating the intracellular concentration of specific proteins to maintain homeostasis within cells. The disruption of 26S proteasome function disrupts normal cellular homeostasis, leading to cytotoxic effect on various kinds of cancer cells. 

Drug for Cancer treatment

Bortezomib is a drug for treatment of hematopoietic malignancies with the appearance being white or white-like crystalline powder. It is easily soluble in dimethyl sulfoxide, ethanol, but insoluble in aqueous solution. This product is the reversible inhibitor of the mammal cell 26S proteasome chymotrypsin-like activity. 26S proteasome is a large protein complex which can degrade ubiquitin. Ubiquitin proteasome pathway plays an important role in regulation of the intracellular concentration of specific proteins in order to maintain the stability of the intracellular environment. Proteolytic affects intracellular multi-level signalling cascade. The disruption of the normal intracellular environment can lead to cell death while the inhibition of the 26S proteasome can prevent the hydrolysis of specific proteins. In vitro tests have proved bortezomib exhibits cytotoxicity to multiple types of cancer cells. The in vivo models of preclinical tumor have proved that bortezomib is capable of delaying the tumor growth of multiple myeloma which is suitable for the treatment of multiple myeloma.
The above information is edited by the Chemicalbook of Dai Xiongfeng.

Description

Bortezomib, a potent ubiquitin proteasome (26S) inhibitor (Ki=0.6 nM), was launched in the US as a treatment for multiple myeloma. This proteasome is required for the proteolytic degradation of the majority of cellular proteins and is present in all cells. It is required for the control of inflammatory processes, cell cycle regulation and gene expression and is a novel target in cancer treatment. Bortezomib is a N-acyl-pseudodipeptidyl boronic acid and formulated as a mannitol ester. Aldehyde containing peptides are also proteasome inhibitors, but lack chiral stability (racemization) and selectivity against other proteases including cysteine proteases. Replacement of the aldehyde moiety by a boronic acid avoids these shortcomings and provides some measure of selective proteasome inhibition relative to many other serine proteases. It is prepared by coupling the pinanediol ester of leucine boronic acid with N-tert-Bocphenylalanine utilizing O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU) as the coupling agent. The tert-Boc protecting group is then cleaved from the dipeptide and pyrazinecarboxylic acid is coupled to form the terminal amide. Hydrolysis of the boronate ester is accomplished via a two-phase transesterification procedure using isobutyl boronic acid and aqueous extraction. In a study of patients who had received at least two prior therapies and demonstrated disease progression on their most recent therapy, about twenty eight percent showed a response to bortezomib. The response lasted a median time of one year. Another trial in 54 patients with relapsed multiple myeloma showed similar responses. It is dosed intravenously at an exposure of 1.3 mg/m2/dose twice weekly for two weeks followed by a 10-day drug-holiday. At therapeutic doses, the plasma drug levels were reported to drop to near detection limits within minutes of intravenous dosing. Based upon an ex vivo proteasome activity assay using blood cells, the pharmacodynamic half-life ranged from 9 to 15 h in patients with advanced malignancies.

Chemical Properties

Yellow Solid

Originator

Millenium (LeukoSite, Proscript) (US)

Uses

A potent, highly selective and reversible inhibitor of the 20S proteasome, Bortezomib is used as an antineoplastic agent, which controls the growth of cancer cells. It is also useful in the treatment of multiple myeloma.

Uses

Bortezomib is the first proteasome inhibitor to be approved b the US FDA for multiple myeloma, a blood cancer. A reversible inhibitor of the 26S proteasome-a barrel-shaped multiprotein particle found in the nucleus and cytosol of all eukaryotic cells. T

Definition

ChEBI: L-Phenylalaninamide substituted at the amide nitrogen by a 1-(dihydroxyboranyl)-3-methylbutyl group and at Nalpha by a pyrazin-2-ylcarbonyl group. It is a dipeptidyl boronic acid tha reversibly inhibits the 26S proteasome.

brand name

Velcade (Millennium).

General Description

Proteasomes normally function to degrade proteins that areno longer needed by the cell. Such proteins are normallymarked by the addition of ubiquitin, a 76 amino acid proteinthat is added to the -amino group of lysine residues onthe target proteins. The marked proteins are then hydrolyzedby the large barrel-shaped proteasomes to givepeptides of 7 to 8 residues that may be further hydrolyzedand reutilized by the cell. This process serves to regulateprotein levels within the cell, remove defective proteins,and becomes important in maintaining normal signal transduction.Inhibition of the proteasomes results in the buildup of ubiquitylated proteins, which disrupts cell-signalingprocesses and cell growth. The signaling bytranscription factor NF-B (nuclear factor B) appears tobe especially sensitive to bortezomib. NF-B is associatedwith the transcription of antiapoptotic and proliferativegenes but is under the control of IB (inhibitor of NF-B).IB can itself be phosphorylated by IKK (IB kinase),which marks IB for ubiquitylation and destruction allowingNF-B to mediate its antiapoptotic and proliferative effects effects.In the presence of the competitive inhibitor bortezomib(IC50=0.6 nM), the 26S proteasome is inhibitedand the ubiquitylated IkB is still capable of inhibiting NF-kB, preventing its effects.

Pharmaceutical Applications

Bortezomib belong to the class of drugs called proteasome inhibitors and is licensed in the United States and the United Kingdom for the treatment of multiple myeloma. The drug has been licensed for patients in whom the myeloma has progressed despite prior treatment or where a bone marrow transplant is not possible or was not successful. It is marketed under the name Velcade? or Cytomib?. Velcade is administered via injection and is sold as powder for reconstitution.
Bortezomib was the first drug approved in the new drug class of proteasome inhibitors and boron seems to be its active element. For the mode of action, it is believed that the boron atom binds with high affinity and specificity to the catalytic site of 26S proteasome and inhibits its action. Therapy with Bortezomib can lead to a variety of adverse reactions, including peripheral neuropathy, myelosuppression, renal impairment and gastrointestinal (GI) disturbances together with changes in taste. Nevertheless, the side effects are in most cases less severe than with alternative treatment options such as bone marrow transplantation.

Biochem/physiol Actions

Cell permeable: yes

Clinical Use

Proteasome inhibitor:

Treatment of multiple myeloma for people who have already tried at least 1 prior therapy and have disease progression

Synthesis

Although the synthesis of dipeptidyl boronic acids have appeared on several reports, the synthetic details for bortezomib were not revealed. The synthetic route for the preparation of bortezomib is depicted in the scheme.The pinanediol ester of leucine boronic acid (56)was coupled with N-Boc phenylalanine (57) in the presence of TBTU followed by deprotection of the Boc group to provide 58. N-Acylation of 58 then furnished the dipeptide boronate ester 60. Deprotection of the boronic ester functionality was achieved by bi-phase transfer esterification with isobutyl boronic acid. Bortezomib (VI) was isolated by extractive workup.

Synthesis_179324-69-7

target

20S proteasome

Drug interactions

Potentially hazardous interactions with other drugs
Antibacterials: potential reduced efficacy with rifampicin resulting in increased monoclonal IgG λ – avoid.
Antipsychotics: avoid with clozapine, increased risk of agranulocytosis.

Metabolism

In vitro studies with human liver microsomes and human cDNA-expressed cytochrome P450 isozymes indicate that bortezomib is primarily oxidatively metabolised via cytochrome P450 enzymes, 3A4, 2C19, and 1A2. The major metabolic pathway is deboronation to form two deboronated metabolites that subsequently undergo hydroxylation to several metabolites. Deboronated-bortezomib metabolites are inactive as 26S proteasome inhibitors.

storage

+4°C

References

1) Adams et al. (1999), Proteasome inhibitors: a novel class of potent and effective antitumor agents; Cancer Res., 59 2615 2) Williams et al. (2003), Differential effects of the proteasome inhibitor bortezomib on apoptosis and angiogenesis in human prostate tumor xenografts; Mol. Cancer Ther., 2 835 3) Richardson et al. (2003), Bortezomib (PS-341): a novel, first-in-class proteasome inhibitor for the treatment of multiple myeloma and other cancers; Cancer Control, 10 361 4) Herve and Ibrahim (2017), Proteasome inhibitors to alleviate aberrant IKBKAP mRNA splicing and low IKAP/hELP1 synthesis in familial dysautonomia; Neurobiol. Dis., 103 113

1029701-48-1
7732-18-5
179324-69-7
Synthesis of Bortezomib from 1029701-48-1 and Water

Bortezomib Preparation Products And Raw materials

Global( 756)Suppliers
Supplier Tel Email Country ProdList Advantage
Chengdu Aslee Biopharmaceuticals, Inc.
28-85305008 CHINA 964 58
AFINE CHEMICALS LIMITED
0571-85134551 info@afinechem.com CHINA 15377 58
Shijiazhuang Tongyang Import and Export Co., LTD
18031361688; admin@sjztongyang.com China 987 58
Hebei Yanxi Chemical Co., Ltd.
+8617531190177 peter@yan-xi.com China 5960 58
Henan Bao Enluo International TradeCo.,LTD
+86-17331933971 +86-17331933971 deasea125996@gmail.com China 2504 58
Shaanxi Haibo Biotechnology Co., Ltd
+86-02963020060 +86-18629295024 hibo06@xaltbio.com China 1000 58
SHANDONG BOYUAN PHARMACEUTICAL CO., LTD.
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Alpha Biopharmaceuticals Co., Ltd
+86-411-39042497 +8613921981412 sales@alphabiopharm.com China 886 58
Frapp's ChemicalNFTZ Co., Ltd.
+86 (576) 8169-6106 sales@frappschem.com China 885 50
Capot Chemical Co.,Ltd.
571-85586718 +8613336195806 sales@capotchem.com China 29797 60

View Lastest Price from Bortezomib manufacturers

Image Update time Product Price Min. Order Purity Supply Ability Manufacturer
Bortezomib pictures 2024-03-16 Bortezomib
179324-69-7
US $0.00 / KG 100g 98%+ 100kg WUHAN CIRCLE POWDER TECHNOLOGY CO.,LTD
Bortezomib pictures 2023-11-08 Bortezomib
179324-69-7
US $0.00 / kg 1kg 99% 2000ton Shaanxi Haibo Biotechnology Co., Ltd
Bortezomib pictures 2023-11-01 Bortezomib
179324-69-7
US $0.00-0.00 / g 1g 99.0% min 100kgs/month Hangzhou ICH Biofarm Co., Ltd
  • Bortezomib pictures
  • Bortezomib
    179324-69-7
  • US $0.00 / KG
  • 98%+
  • WUHAN CIRCLE POWDER TECHNOLOGY CO.,LTD
  • Bortezomib pictures
  • Bortezomib
    179324-69-7
  • US $0.00 / kg
  • 99%
  • Shaanxi Haibo Biotechnology Co., Ltd
  • Bortezomib pictures
  • Bortezomib
    179324-69-7
  • US $0.00-0.00 / g
  • 99.0% min
  • Hangzhou ICH Biofarm Co., Ltd
Boronic acid, B-[(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(2-pyrazinylcarbonyl)aMino]propyl]aMino]bu MG-341 PS-341 BortezoMib Base bortezoMib(other) MLM341 BortezoMib R VELCADE(BORTEZOMIB) Boronic acid, B-[(1R)-3-methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(2-pyrazinylcarbonyl)amino]propyl]amino]butyl]- Bortezomib for research Bortezomib ( Velcade, MG-341, PS-341 ) (R)-3-methyl-1-((S)-3-phenyl-2-(pyrazine-5-carboxamido)propanamido)butylboronic acid BORTEZOMIB; MG-341; PS-341 BortezoMib(Velcade) BortezoMib for res BortezMib 10MG/50MG/1G N-pyrazinoyl-L-phenylalanine-L-boronoleucine [(1S)-3-Methyl-1-[(2R)-3-phenyl-2-(pyrazin-2-ylforMaMido)propanaMido]butyl]boronic acid Radiciol BortezoMib (PS-341, LDP-341, MLM341) BortezoMib (PS-341) chloro-4-fluoro-phenyl)aMino]-6-nitro-7-[(S)-(tetrahydrofuran-3-yl)oxy]quinazolin N-(2-Pyrazinecarbonyl)-L-phenylalanine-L-leucine boronic anhydride B-[(1R)-3-methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(2-pyrazinylcarbonyl)amino]propyl]amino]butyl]-boronic acid DPBA Bortezomib (PS-341) Bortezomib [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]-boronic acid EZSolution PS-341 Bortezomib, >=98% BORTEZOMIB [(1r)-3-methyl-1-[[(2s)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]-boronic acid Bortezomib (Intermediate in China ONLY) CS-1886 3-methyl-1-((S)-3-phenyl-2-(pyrazine-2-carboxamido)propanamido)butylboronic acid Bortezomib for Injection Brotezamide Bortezomib USP/EP/BP ortezomib Bortezomib (10mM in DMSO) bortezomib working std Bortezomib D8Q: What is Bortezomib D8 Q: What is the CAS Number of Bortezomib D8 Q: What is the storage condition of Bortezomib D8 Q: What are the applications of Bortezomib D8 BortezomibQ: What is Bortezomib Q: What is the CAS Number of Bortezomib Q: What is the storage condition of Bortezomib Q: What are the applications of Bortezomib BortezoMib-D8 ((R)-3-Methyl-1-((S)-3-phenyl-2-(pyrazine-2-carboxaMido)propanaMido)butyl)boronic acid VELCADE dpba Bortezomib Boronic acid, B-[(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(2-pyrazinylcarbonyl)aMino]propyl]aMino]bu Bortezomib(Trimeric Boroxine Form) (R) -3-Methyl-1-((S)-3-phenyl-2-(pyrazine-2-carboxamido) propanamido)-butyl boronic acid Bortizomib Bortezomi API Bozomi Nuclear factor-kappaB,Inhibitor,Nuclear factor-κB,Apoptosis,PS 341,PS341,Autophagy,Proteasome,NSC-681239,LDP341,PS-341,inhibit,NF-κB,Bortezomib,LDP-341,NSC681239 Bortezomib 99% Bortezomib API Bortzeomib solution (10mM/L) 179324-69-7 79324-69-7 C19H25BN4O4 peptides