Bortezomib (PS-341)

Names

[ Name ]:
Bortezomib (PS-341)

[Synonym ]:
[(1R)-3-methyl-1-({(2S)-3-phenyl-2-[(pyrazin-2-ylcarbonyl)amino]propanoyl}amino)butyl]boronic acid
Radiciol
boronic acid, [(1R)-3-methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]-
Bortezomib
dpba
BortezMib
N-[(1R)-1-(Dihydroxyboryl)-3-methylbutyl]-Nα-(pyrazin-2-ylcarbonyl)-L-phenylalaninamide
MFCD05260688
BortezoMib-D8
Boronic acid, ((1R)-3-methyl-1-(((2S)-1-oxo-3-phenyl-2-((pyrazinylcarbonyl)amino)propyl)amino)butyl)-
N-[(1R)-1-(Dihydroxyboryl)-3-methylbutyl]-Nα-(2-pyrazinylcarbonyl)-L-phenylalaninamide
Velcade
N-[(1R)-1-(dihydroxyboranyl)-3-methylbutyl]-Nα-(pyrazin-2-ylcarbonyl)-L-phenylalaninamide
Boronic acid, B-[(1R)-3-methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(2-pyrazinylcarbonyl)amino]propyl]amino]butyl]-
BortezoMib Base
MG-341 PS-341
BortezoMib for res

Biological Activity

[Description]:

Bortezomib (PS-341) is a potent 20S proteasome inhibitor with a Ki of 0.6 nM.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Metabolic Enzyme/Protease >> Proteasome

Research Areas >> Cancer

[Target]

Ki: 0.6 nM (20S proteasome)[1]

[In Vitro]

Bortezomib (PS-341) effects proteins that control cell cycle progression. Treatment of PC-3 cells with Bortezomib (100 nM) for 8 h results in the accumulation of cells in G2-M, with a corresponding decrease in the number of cells in G1. The Bortezomib doses at which 50% of PC-3 cells are killed at 24 and 48 h are determined to be 100 and 20 nM, respectively[1]. Bortezomib is a highly selective, reversible inhibitor of the 26S proteasome. Inhibition of the proteasome by Bortezomib results in activation of JNK, stabilization of p53, Bid, Bax, p21, p27, caveolin-1, and IκBα, resulting in inhibition of NF-κB[2]. The IC50 of Bortezomib is found to be 2.46 nM for 26S proteasome in the B16F10 cells[3].

[In Vivo]

Mice bearing PC-3 tumors are treated with Bortezomib (i.v., 0.3 or 1.0 mg/kg). Bortezomib (1.0 mg/kg) results in a significant decrease in tumor growth ~60%. Bortezomib (0.3 mg/kg) produces a 16% decrease in tumor volume but did not reach significance[1]. Bortezomib (0.2 mg/kg) significantly decreases the withdrawal threshold on days 11 and 15 and increases the number of withdrawal responses on days 11 and 15 compared with the vehicle group in the von Frey and acetone tests[4].

[Cell Assay]

The human PC-3 prostate tumor cells are treated with Bortezomib (0.1 nM, 1 nM, 10 nM, 100 nM, 1 μM, 10 μM) for 24-48 h in complete medium. Cytotoxicity is measured using a MTT assay[1].

[Animal admin]

Mice[1] Male nude mice (18-20 g; n=51) are used. Bortezomib (0.3 or 1.0 mg/kg) is administered in vehicle i.v. using a dose volume of 100 μL per mouse or directly into the tumor in a 10 μL volume. Due to the comparatively high levels of Bortezomib in the prostate, after i.v. dosing of radiolabeled drug, it is decided to examine the effects of this novel compound in the prostate, PC-3, xenograft tumor model. Animals are treated when the tumors become palpable (>300 mm3). Male nude mice (18-20 g; n=51) are used. Bortezomib (0.3 or 1.0 mg/kg) is administered in vehicle i.v. using a dose volume of 100 μL per mouse or directly into the tumor in a 10 μL volume. Due to the comparatively high levels of Bortezomib in the prostate, after i.v. dosing of radiolabeled drug, it is decided to examine the effects of this novel compound in the prostate, PC-3, xenograft tumor model. Animals are treated when the tumors become palpable (>300 mm3). Rats[4] Male Sprague-Dawley rats weighing 200-250 g are used. Bortezomib (0.05, 0.1, or 0.2 mg/kg) or vehicle (5% DMSO solution) is administered intraperitoneally (i.p.) twice a week for 2 weeks (on days 1, 4, 8, and 11). The administration schedule and doses of Bortezomib are determined based on clinical treatment (1.3 mg/m2 of Bortezomib on days 1, 4, 8, and 11).

[References]

[1]. Adams J, et al. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res. 1999 Jun 1;59(11):2615-22.

[2]. Boccadoro M, et al. Preclinical evaluation of the proteasome inhibitor bortezomib in cancer therapy. Cancer Cell Int. 2005 Jun 1;5(1):18.

[3]. Yerlikaya A, et al. Combined effects of the proteasome inhibitor bortezomib and Hsp70 inhibitors on the B16F10 melanoma cell line. Mol Med Rep. 2010 Mar-Apr;3(2):333-9.

[4]. Yamamoto S, et al. Behavioral and pharmacological characteristics of bortezomib-induced peripheral neuropathy in rats. J Pharmacol Sci. 2015 Sep;129(1):43-50.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Melting Point ]:
122-124°C

[ Molecular Formula ]:
C₁₉H₂₅BN₄O₄

[ Molecular Weight ]:
384.237

[ Exact Mass ]:
384.196899

[ PSA ]:
124.44000

[ LogP ]:
2.45

[ Index of Refraction ]:
1.564

[ Storage condition ]:
Hygroscopic, -20°C Freezer, Under Inert Atmosphere

[ Stability ]:
Hygroscopic and Moisture Sensitive

Safety Information

[ Hazard Codes ]:
Xi

[ Safety Phrases ]:
S26-S36/37/39

[ RIDADR ]:
3261

[ HS Code ]:
2934999090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2934999090

[ Summary ]:
2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%