Bortezomib 1PC X 5MG

Biochem/physiol Actions

Reversible: yes

Cell permeable: yes

General description

A cell-permeable dipeptidylboronate compound that selectively inhibits 20S proteasome β5 ChTL/chymotrypsin- over β1 CL/caspase- and β2 TL/trypsin-like activity (k_inact/K_i = 38,000, 5,700, and ﹤100 M^-1s^-1, respectively, in human 20S proteasome assays using 10 M Suc-LLVY-AMC/Cat. No. 539142, 10 M Z-LLE-AMC/Cat. No. 539141, or 50 M Boc-LRR-AMC as substrate) via a covalent, slowly reversible manner, displaying much reduced potency against human chymotrypsin, cathepsin G, leukocyte elastase, and thrombin (K_i = 0.32, 0.63, 2.3, and 13 M, respectively, vs. 620 nM using rabbit muscle 20S). A widely used inhibitor both in cultures in vitro and in animals in vivo.

A cell-permeable dipeptidylboronate compound that selectively inhibits 20S proteasome β5 ChTL/chymotrypsin- over β1 CL/caspase- and β2 TL/trypsin-like activity (k_inact/K_i = 38,000, 5,700, and ﹤100 M^-1s^-1, respectively, in human 20S proteasome assays using 10 M Suc-LLVY-AMC/Cat. No. 539142, 10 M Z-LLE-AMC/Cat. No. 539141, or 50 M Boc-LRR-AMC as substrate; IC₅₀ in 1 h = 7, 74, and 4,200 nM, respectively) via a covalent, slowly reversible, interaction between the nucleophilic Thr1 hydroxy group/Thr1O^γ of the catalytic β subunit and the inhibitor′s electrophilic boronic moiety, displaying much reduced potency against human chymotrypsin, cathepsin G, leukocyte elastase, and thrombin (K_i = 0.32, 0.63, 2.3, and 13 M, respectively, vs. 620 nM using rabbit muscle 20S). A widely used inhibitor both in cultures in vitro and in animals in vivo. Despite being the first proteasome inhibitor approved by FDA for clinical anticancer treatment, its therapeutic efficacy continues to be hampered by off-target effects and dose-limiting toxicity.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Du, X.L, and Chen, Q. 2013. Acta Haematol.129, 207.Tamatani, T., et al. 2013. Int. J. Oncol.42, 935.Beck, P., et al. 2012. J. Biol. Chem.393, 1101. Fang, H.T., et al. 2012. Proc. Natl. Acad. Sci. USA.109, 2521.Chen, D., et al. 2011. Curr. Cancer Drug Targets11, 239.Demo, S.D., et al. 2007. Cancer Res.67, 6383.Adams, J., et al. 1999. Cancer Res.59, 2615.Teicher, B.A., et al. 1999. Clin. Cancer Res.5, 2638.Adams, J., et al. 1998. Bioorg. Med. Chem. Lett.8, 333.

Packaging

5 mg in Glass bottle

Packaged under inert gas

Preparation Note

Use only fresh DMSO or Ethanol for reconstitution.

Reconstitution

Following reconstitution, aliquot and freeze (-20°C.) Stock solutions are stable for up to 6 months at -20°C.

Warning

Toxicity: Standard Handling (A)