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Chemical Compound Review

Velcade     [(1S)-3-methyl-1-[[(2R)-3- phenyl-2...

Synonyms: SureCN3676, Velcade (TN), LPD-341, MLN-341, S1013_Selleck, ...
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Disease relevance of Ps 341


High impact information on Ps 341

  • These can be targeted by specific modulators such as bortezomib, and mammalian target of rapamycin inhibitors such as CCI-779 and RAD 001 [6].
  • Treatment with the proteasome inhibitors MG132 and bortezomib increased WASP levels in T cells from WIP(-/-) mice and in T and B lymphocytes from two WAS patients with missense mutations (R86H and T45M) that disrupt WIP binding [7].
  • The anti-tumor activity of IPI-504 was tested as both a single agent as well as in combination with bortezomib in myeloma cell lines and in vivo xenograft models, and the retention of IPI-504 in tumor tissue was determined [8].
  • To prove this hypothesis, we used bortezomib and tubacin to inhibit the proteasome and HDAC6, respectively [3].
  • We found that bortezomib potently inhibited in vitro mixed lymphocyte responses and promoted the apoptosis of alloreactive T cells [9].

Chemical compound and disease context of Ps 341


Biological context of Ps 341


Anatomical context of Ps 341

  • Assessment of graft-versus-tumor responses in advanced leukemia-bearing mice demonstrated that only the combination of allogeneic BMT and T cells with bortezomib promoted significant increases in survival [9].
  • Importantly, normal B lymphocytes were not sensitized to TRAIL by either Dox, SN50, or PS-341 [19].
  • Using biochemical and microarray approaches, we found that proteasome inhibition by PS-341 induced endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) in HNSCC cells [20].
  • Targeting mitochondria to overcome conventional and bortezomib/proteasome inhibitor PS-341 resistance in multiple myeloma (MM) cells [21].
  • Here, we show that bortezomib, a proteasome inhibitor with anticancer activity, impairs several immune properties of human monocyte-derived dendritic cells (DCs) [22].

Associations of Ps 341 with other chemical compounds


Gene context of Ps 341


Analytical, diagnostic and therapeutic context of Ps 341

  • Using bioluminescence imaging after one dose of the chemo-therapeutic proteasome inhibitor bortezomib (PS-341), proteasome function in tumor xenografts was blocked within 30 min and returned to nearly baseline by 46 h [30].
  • These data provide both insight into the molecular mechanisms of antitumor activity of PS-341 and the rationale for future clinical trials of PS-341, in combination with conventional and novel therapies, to improve patient outcome in MM [15].
  • These results demonstrate the key role played by NF-kappaB in the resistance of CTCL to apoptosis and suggest that bortezomib might be useful for the treatment of patients with advanced stages of CTCL refractory to standard antineoplastic chemotherapy [31].
  • In conclusion, in elderly patients ineligible for transplantation, the combination of bortezomib plus MP appears significantly superior to MP, producing very high CR rates, including immunophenotypic CRs, even in patients with poor prognostic features [12].
  • Synergistic activity of the proteasome inhibitor PS-341 with non-myeloablative 153-Sm-EDTMP skeletally targeted radiotherapy in an orthotopic model of multiple myeloma [32].


  1. Proteasome inhibition in multiple myeloma: therapeutic implication. Chauhan, D., Hideshima, T., Anderson, K.C. Annu. Rev. Pharmacol. Toxicol. (2005) [Pubmed]
  2. The proteasome and proteasome inhibitors in cancer therapy. Voorhees, P.M., Orlowski, R.Z. Annu. Rev. Pharmacol. Toxicol. (2006) [Pubmed]
  3. Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma. Hideshima, T., Bradner, J.E., Wong, J., Chauhan, D., Richardson, P., Schreiber, S.L., Anderson, K.C. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  4. Role of the proteasome and NF-kappaB in streptococcal cell wall-induced polyarthritis. Palombella, V.J., Conner, E.M., Fuseler, J.W., Destree, A., Davis, J.M., Laroux, F.S., Wolf, R.E., Huang, J., Brand, S., Elliott, P.J., Lazarus, D., McCormack, T., Parent, L., Stein, R., Adams, J., Grisham, M.B. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  5. Experience with bortezomib for the treatment of patients with relapsed classical Hodgkin lymphoma. Younes, A., Pro, B., Fayad, L. Blood (2006) [Pubmed]
  6. Targeting apoptosis pathways in cancer therapy. Ghobrial, I.M., Witzig, T.E., Adjei, A.A. CA: a cancer journal for clinicians. (2005) [Pubmed]
  7. WIP is a chaperone for Wiskott-Aldrich syndrome protein (WASP). de la Fuente, M.A., Sasahara, Y., Calamito, M., Antón, I.M., Elkhal, A., Gallego, M.D., Suresh, K., Siminovitch, K., Ochs, H.D., Anderson, K.C., Rosen, F.S., Geha, R.S., Ramesh, N. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  8. Development of 17-allylamino-17-demethoxygeldanamycin hydroquinone hydrochloride (IPI-504), an anti-cancer agent directed against Hsp90. Sydor, J.R., Normant, E., Pien, C.S., Porter, J.R., Ge, J., Grenier, L., Pak, R.H., Ali, J.A., Dembski, M.S., Hudak, J., Patterson, J., Penders, C., Pink, M., Read, M.A., Sang, J., Woodward, C., Zhang, Y., Grayzel, D.S., Wright, J., Barrett, J.A., Palombella, V.J., Adams, J., Tong, J.K. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  9. Inhibition of acute graft-versus-host disease with retention of graft-versus-tumor effects by the proteasome inhibitor bortezomib. Sun, K., Welniak, L.A., Panoskaltsis-Mortari, A., O'Shaughnessy, M.J., Liu, H., Barao, I., Riordan, W., Sitcheran, R., Wysocki, C., Serody, J.S., Blazar, B.R., Sayers, T.J., Murphy, W.J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  10. SDX-101, the R-enantiomer of etodolac, induces cytotoxicity, overcomes drug resistance, and enhances the activity of dexamethasone in multiple myeloma. Yasui, H., Hideshima, T., Hamasaki, M., Roccaro, A.M., Shiraishi, N., Kumar, S., Tassone, P., Ishitsuka, K., Raje, N., Tai, Y.T., Podar, K., Chauhan, D., Leoni, L.M., Kanekal, S., Elliott, G., Munshi, N.C., Anderson, K.C. Blood (2005) [Pubmed]
  11. Remarkable activity of novel agents bortezomib and thalidomide in patients not responding to donor lymphocyte infusions following nonmyeloablative allogeneic stem cell transplantation in multiple myeloma. van de Donk, N.W., Kröger, N., Hegenbart, U., Corradini, P., San Miguel, J.F., Goldschmidt, H., Perez-Simon, J.A., Zijlmans, M., Raymakers, R.A., Montefusco, V., Ayuk, F.A., van Oers, M.H., Nagler, A., Verdonck, L.F., Lokhorst, H.M. Blood (2006) [Pubmed]
  12. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Mateos, M.V., Hernández, J.M., Hernández, M.T., Gutiérrez, N.C., Palomera, L., Fuertes, M., Díaz-Mediavilla, J., Lahuerta, J.J., de la Rubia, J., Terol, M.J., Sureda, A., Bargay, J., Ribas, P., de Arriba, F., Alegre, A., Oriol, A., Carrera, D., García-Laraña, J., García-Sanz, R., Bladé, J., Prósper, F., Mateo, G., Esseltine, D.L., van de Velde, H., Miguel, J.F. Blood (2006) [Pubmed]
  13. The tyrphostin adaphostin interacts synergistically with proteasome inhibitors to induce apoptosis in human leukemia cells through a reactive oxygen species (ROS)-dependent mechanism. Dasmahapatra, G., Rahmani, M., Dent, P., Grant, S. Blood (2006) [Pubmed]
  14. Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition. Cusack, J.C., Liu, R., Houston, M., Abendroth, K., Elliott, P.J., Adams, J., Baldwin, A.S. Cancer Res. (2001) [Pubmed]
  15. Molecular sequelae of proteasome inhibition in human multiple myeloma cells. Mitsiades, N., Mitsiades, C.S., Poulaki, V., Chauhan, D., Fanourakis, G., Gu, X., Bailey, C., Joseph, M., Libermann, T.A., Treon, S.P., Munshi, N.C., Richardson, P.G., Hideshima, T., Anderson, K.C. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  16. The fully human anti-CD30 antibody 5F11 activates NF-{kappa}B and sensitizes lymphoma cells to bortezomib-induced apoptosis. Böll, B., Hansen, H., Heuck, F., Reiners, K., Borchmann, P., Rothe, A., Engert, A., Pogge von Strandmann, E. Blood (2005) [Pubmed]
  17. Bortezomib and flavopiridol interact synergistically to induce apoptosis in chronic myeloid leukemia cells resistant to imatinib mesylate through both Bcr/Abl-dependent and -independent mechanisms. Dai, Y., Rahmani, M., Pei, X.Y., Dent, P., Grant, S. Blood (2004) [Pubmed]
  18. The bortezomib/proteasome inhibitor PS-341 and triterpenoid CDDO-Im induce synergistic anti-multiple myeloma (MM) activity and overcome bortezomib resistance. Chauhan, D., Li, G., Podar, K., Hideshima, T., Shringarpure, R., Catley, L., Mitsiades, C., Munshi, N., Tai, Y.T., Suh, N., Gribble, G.W., Honda, T., Schlossman, R., Richardson, P., Sporn, M.B., Anderson, K.C. Blood (2004) [Pubmed]
  19. TRAIL/Apo2L ligand selectively induces apoptosis and overcomes drug resistance in multiple myeloma: therapeutic applications. Mitsiades, C.S., Treon, S.P., Mitsiades, N., Shima, Y., Richardson, P., Schlossman, R., Hideshima, T., Anderson, K.C. Blood (2001) [Pubmed]
  20. Proteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cells. Fribley, A., Zeng, Q., Wang, C.Y. Mol. Cell. Biol. (2004) [Pubmed]
  21. Targeting mitochondria to overcome conventional and bortezomib/proteasome inhibitor PS-341 resistance in multiple myeloma (MM) cells. Chauhan, D., Li, G., Podar, K., Hideshima, T., Mitsiades, C., Schlossman, R., Munshi, N., Richardson, P., Cotter, F.E., Anderson, K.C. Blood (2004) [Pubmed]
  22. Proteasome inhibitor bortezomib modulates TLR4-induced dendritic cell activation. Nencioni, A., Schwarzenberg, K., Brauer, K.M., Schmidt, S.M., Ballestrero, A., Grünebach, F., Brossart, P. Blood (2006) [Pubmed]
  23. A neurotrophin axis in myeloma: TrkB and BDNF promote tumor-cell survival. Pearse, R.N., Swendeman, S.L., Li, Y., Rafii, D., Hempstead, B.L. Blood (2005) [Pubmed]
  24. Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma. Raje, N., Kumar, S., Hideshima, T., Roccaro, A., Ishitsuka, K., Yasui, H., Shiraishi, N., Chauhan, D., Munshi, N.C., Green, S.R., Anderson, K.C. Blood (2005) [Pubmed]
  25. The proteasome inhibitor bortezomib interacts synergistically with histone deacetylase inhibitors to induce apoptosis in Bcr/Abl+ cells sensitive and resistant to STI571. Yu, C., Rahmani, M., Conrad, D., Subler, M., Dent, P., Grant, S. Blood (2003) [Pubmed]
  26. Caveolin-1 is required for vascular endothelial growth factor-triggered multiple myeloma cell migration and is targeted by bortezomib. Podar, K., Shringarpure, R., Tai, Y.T., Simoncini, M., Sattler, M., Ishitsuka, K., Richardson, P.G., Hideshima, T., Chauhan, D., Anderson, K.C. Cancer Res. (2004) [Pubmed]
  27. Bortezomib abolishes tumor necrosis factor-related apoptosis-inducing ligand resistance via a p21-dependent mechanism in human bladder and prostate cancer cells. Lashinger, L.M., Zhu, K., Williams, S.A., Shrader, M., Dinney, C.P., McConkey, D.J. Cancer Res. (2005) [Pubmed]
  28. Bortezomib inhibits cell-cell adhesion and cell migration and enhances epidermal growth factor receptor inhibitor-induced cell death in squamous cell cancer. Lorch, J.H., Thomas, T.O., Schmoll, H.J. Cancer Res. (2007) [Pubmed]
  29. PS-341 or a combination of arsenic trioxide and interferon-alpha inhibit growth and induce caspase-dependent apoptosis in KSHV/HHV-8-infected primary effusion lymphoma cells. Abou-Merhi, R., Khoriaty, R., Arnoult, D., El Hajj, H., Dbouk, H., Munier, S., El-Sabban, M.E., Hermine, O., Gessain, A., de Thé, H., Mahieux, R., Bazarbachi, A. Leukemia (2007) [Pubmed]
  30. Imaging 26S proteasome activity and inhibition in living mice. Luker, G.D., Pica, C.M., Song, J., Luker, K.E., Piwnica-Worms, D. Nat. Med. (2003) [Pubmed]
  31. Down-regulating constitutive activation of the NF-kappaB canonical pathway overcomes the resistance of cutaneous T-cell lymphoma to apoptosis. Sors, A., Jean-Louis, F., Pellet, C., Laroche, L., Dubertret, L., Courtois, G., Bachelez, H., Michel, L. Blood (2006) [Pubmed]
  32. Synergistic activity of the proteasome inhibitor PS-341 with non-myeloablative 153-Sm-EDTMP skeletally targeted radiotherapy in an orthotopic model of multiple myeloma. Goel, A., Dispenzieri, A., Geyer, S.M., Greiner, S., Peng, K.W., Russell, S.J. Blood (2006) [Pubmed]
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