b-AP15
b-AP15 is a novel inhibitor of proteasome deubiquitination. b-AP15 displays antitumor activity in several preclinical, solid tumor models. b-AP15 triggers time- and dose-dependent apoptosis of the human multiple myeloma (MM) cell lines RPMI8226 and U266, as determined by phosphatidylserine exposure. Furthermore, b-AP15 triggered processing of pro-caspase-3 and cleavage of poly (ADP-ribose) polymerase in MM cells. b-AP15 also induced caspase-independent apoptosis in primary human natural killer cells. b-AP15 may have potential for treatment of multiple myeloma patients.
1: Tian Z, D'Arcy P, Wang X, Ray A, Tai YT, Hu Y, Carrasco RD, Richardson P, Linder S, Chauhan D, Anderson KC. A novel small molecule inhibitor of deubiquitylating enzyme USP14 and UCHL5 induces apoptosis in multiple myeloma and overcomes bortezomib resistance. Blood. 2014 Jan 30;123(5):706-16. doi: 10.1182/blood-2013-05-500033. Epub 2013 Dec 6. PubMed PMID: 24319254.
2: Feng X, Holmlund T, Zheng C, Fadeel B. Proapoptotic effects of the novel proteasome inhibitor b-AP15 on multiple myeloma cells and natural killer cells. Exp Hematol. 2013 Nov 27. pii: S0301-472X(13)00871-0. doi: 10.1016/j.exphem.2013.11.010. [Epub ahead of print] PubMed PMID: 24291587.
3: Brnjic S, Mazurkiewicz M, Fryknäs M, Sun C, Zhang X, Larsson R, D'Arcy P, Linder S. Induction of Tumor Cell Apoptosis by a Proteasome Deubiquitinase Inhibitor Is Associated with Oxidative Stress. Antioxid Redox Signal. 2013 Oct 17. [Epub ahead of print] PubMed PMID: 24011031.
4: Sarhan D, Wennerberg E, D'Arcy P, Gurajada D, Linder S, Lundqvist A. A novel inhibitor of proteasome deubiquitinating activity renders tumor cells sensitive to TRAIL-mediated apoptosis by natural killer cells and T cells. Cancer Immunol Immunother. 2013 Aug;62(8):1359-68. doi: 10.1007/s00262-013-1439-1. Epub 2013 May 21. PubMed PMID: 23689729.
5: D'Arcy P, Linder S. Proteasome deubiquitinases as novel targets for cancer therapy. Int J Biochem Cell Biol. 2012 Nov;44(11):1729-38. doi: 10.1016/j.biocel.2012.07.011. Epub 2012 Jul 20. Review. PubMed PMID: 22819849.
6: D'Arcy P, Brnjic S, Olofsson MH, Fryknäs M, Lindsten K, De Cesare M, Perego P, Sadeghi B, Hassan M, Larsson R, Linder S. Inhibition of proteasome deubiquitinating activity as a new cancer therapy. Nat Med. 2011 Nov 6;17(12):1636-40. doi: 10.1038/nm.2536. PubMed PMID: 22057347.
2: Feng X, Holmlund T, Zheng C, Fadeel B. Proapoptotic effects of the novel proteasome inhibitor b-AP15 on multiple myeloma cells and natural killer cells. Exp Hematol. 2013 Nov 27. pii: S0301-472X(13)00871-0. doi: 10.1016/j.exphem.2013.11.010. [Epub ahead of print] PubMed PMID: 24291587.
3: Brnjic S, Mazurkiewicz M, Fryknäs M, Sun C, Zhang X, Larsson R, D'Arcy P, Linder S. Induction of Tumor Cell Apoptosis by a Proteasome Deubiquitinase Inhibitor Is Associated with Oxidative Stress. Antioxid Redox Signal. 2013 Oct 17. [Epub ahead of print] PubMed PMID: 24011031.
4: Sarhan D, Wennerberg E, D'Arcy P, Gurajada D, Linder S, Lundqvist A. A novel inhibitor of proteasome deubiquitinating activity renders tumor cells sensitive to TRAIL-mediated apoptosis by natural killer cells and T cells. Cancer Immunol Immunother. 2013 Aug;62(8):1359-68. doi: 10.1007/s00262-013-1439-1. Epub 2013 May 21. PubMed PMID: 23689729.
5: D'Arcy P, Linder S. Proteasome deubiquitinases as novel targets for cancer therapy. Int J Biochem Cell Biol. 2012 Nov;44(11):1729-38. doi: 10.1016/j.biocel.2012.07.011. Epub 2012 Jul 20. Review. PubMed PMID: 22819849.
6: D'Arcy P, Brnjic S, Olofsson MH, Fryknäs M, Lindsten K, De Cesare M, Perego P, Sadeghi B, Hassan M, Larsson R, Linder S. Inhibition of proteasome deubiquitinating activity as a new cancer therapy. Nat Med. 2011 Nov 6;17(12):1636-40. doi: 10.1038/nm.2536. PubMed PMID: 22057347.
| Chemical | |
|---|---|
| CAS Num | 1009817-63-3 |
| Chemical Formula | C22H17N3O6 |
| Molecular Weight | 419.39 |
| IUPAC Chemical Name | (3E,5E)-1-acryloyl-3,5-bis(4-nitrobenzylidene)piperidin-4-one. |
| Exact Mass | 419.11174 |
| Elemental Analysis | C, 63.01; H, 4.09; N, 10.02; O, 22.89 |
| Synonym | b-AP15; b-AP15; b-AP-15; USP14 Inhibitor III; UCHL5UCH37 Inhibitor II; NSC687852. |
| Solubility | Soluble in DMSO, not in water |
| SMILES Code | O=C1/C(CN(C(C=C)=O)C/C1=C\C2=CC=C([N+]([O-])=O)C=C2)=C/C3=CC=C([N+]([O-])=O)C=C3 |
| Biological | |
| Targets and Effects | N/A |
| Pathways | Apoptosis |
| Physical | |
| Appearance | Yellow solid powder |
| Purity | >98% (or refer to the Certificate of Analysis) |
| Shipping Condition | Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs. |
| Storage Condition | Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years). |
| Shelf Life | >2 years if stored properly |
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