Bortezomib (PS-341)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Bortezomib是一种有效的、特异性的可逆性蛋白酶体抑制剂。它可以抑制H460细胞(人非小细胞肺癌细胞系)的增值,IC50值为0.1 μM。
Bortezomib (PS-341)是第一个用于人体试验的治疗性蛋白酶体抑制剂。Bortezomib被美国批准用于治疗复发性多发性骨髓瘤和套细胞淋巴瘤[1]。Bortezomib是N端受保护的二肽,可以写成Pyz-Phe-boroLeu,分别代表吡嗪酸、苯丙氨酸和以硼酸代替羧酸的亮氨酸。Bortezomib对蛋白酶体的抑制可能涉及多个机制。在依赖于抑制促凋亡途径的肿瘤细胞中,蛋白酶体被抑制后可以阻止促凋亡因子的降解,从而激活程序性细胞死亡。最近研究发现,Bortezomib可以引起由蛋白酶体产生的细胞内多肽水平的快速且剧烈的变化[2]。细胞内的某些多肽是具有生物活性的,因此Bortezomib对细胞内多肽水平的影响可能是该药物的生物学效应,也可能是副作用。
参考文献:
1. Takimoto CH, Calvo E. "Principles of Oncologic Pharmacotherapy" in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) Cancer Management: A Multidisciplinary Approach. 11 ed. 2008.
2. Gelman JS, Sironi J, Berezniuk I, Dasgupta S, Castro LM, Gozzo FC, Ferro ES, Fricker LD (2013). "Alterations of the intracellular peptidome in response to the proteasome inhibitor bortezomib". In Gartel, Andrei L. PLoS One 8 (8): e53263.
- 1. Mikhail S. Chesnokov, Marianna Halasi, et al. "Novel FOXM1 inhibitor identified via gene network analysis induces autophagic FOXM1 degradation to overcome chemoresistance of human cancer cells." Cell Death Dis. 2021 Jul 14;12(7):704. PMID:34262016
- 2. Qi Zhu, Xu-xu Zhuang, et al. "Lycorine, a natural alkaloid, promotes the degradation of alpha-synuclein via PKA-mediated UPS activation in transgenic Parkinson's disease models." Phytomedicine. 2021 Jul;87:153578. PMID:34038839
- 3. David Romero-Suarez, Tune Wulff, et al. "A Reporter System for Cytosolic Protein Aggregates in Yeast." ACS Synth Biol. 2021 Mar 19;10(3):466-477. PMID:33577304
- 4. Yue Peng, Xiaofeng Sun, et al. "Role of DNA methylation on human CTSG in dermatomyositic myoideum." Cell Biol Int. 2020 Dec;44(12):2409-2415. PMID:32813288
- 5. Dana Mamriev, Ruqaia Abbas, et al. "A small-molecule ARTS mimetic promotes apoptosis through degradation of both XIAP and Bcl-2." Cell Death Dis. 2020 Jun 25;11(6):483. PMID:32587235
- 6. Haiyang Yu, Shan Lu, et al. "TDP-43 and HSP70 phase separate into anisotropic, intranuclear liquid spherical annuli." bioRxiv. March 29, 2020.
- 7. Tsai YJ, Hao CY, et al. "Expression of long pentraxin 3 in human nasal mucosa fibroblasts, tissues, and secretions of chronic rhinosinusitis without nasal polyps." J Mol Med (Berl). 2020;98(5):673-689. PMID:32239253
- 8. Lin J, Boon L, et al. "Desensitization using imlifidase and EndoS enables chimerism induction in allosensitized recipient mice." Am J Transplant. 2020;10.1111/ajt.15851. PMID:32185855
- 9. Tracy Cai X, Li H, et al. "AWD regulates timed activation of BMP signaling in intestinal stem cells to maintain tissue homeostasis." Nat Commun. 2019 Jul 5;10(1):2988. PMID:31278345
- 10. Timms RT, Zhang Z, et al. "A glycine-specific N-degron pathway mediates the quality control of protein N-myristoylation." Science. 2019 Jul 5;365(6448). pii: eaaw4912. PMID:31273098
- 11. SemraUnalad, SemaArslanc, et al. "Design and characterization of polycaprolactone-gelatin-graphene oxide scaffolds for drug influence on glioblastoma cells." European Polymer Journal. Volume 115, June 2019, Pages 157-165.
- 12. Rodriguez-Fernandez IA, Qi Y, et al. "Loss of a proteostatic checkpoint in intestinal stem cells contributes to age-related epithelial dysfunction." Nat Commun. 2019 Mar 5;10(1):1050. PMID:30837466
- 13. Yuan NN, Cai CZ, et al. "Canthin-6-One Accelerates Alpha-Synuclein Degradation by Enhancing UPS Activity: Drug Target Identification by CRISPR-Cas9 Whole Genome-Wide Screening Technology." Front Pharmacol. 2019 Jan 28;10:16.nbsp;PMID:30745870
- 14. Cui-ZanCai, He-FengZhou, et al. "Natural alkaloid harmine promotes degradation of Alpha-synuclein via PKA-mediated ubiquitin-proteasome system activation." Phytomedicine. Available online 30 January 2019, 152842.
- 15. Ayse Tarbin Jannuzzi, Gulce Sari, et al. "Proteasomal Inhibition with Bortezomib Causes Selective Autophagy Upregulation and Perinuclear Clustering of Mitochondria in Human Neuronal Cells†." Proceedings 2018, 2(25), 1583.
- 16. Gibbs DJ, Tedds HM, et al. "Oxygen-dependent proteolysis regulates the stability of angiosperm polycomb repressive complex 2 subunit VERNALIZATION 2." Nat Commun. 2018 Dec 21;9(1):5438. PMID:30575749
- 17. Oladimeji PO, Wright WC, et al. "RNA interference screen identifies NAA10 as a regulator of PXR transcription." Biochem Pharmacol. 2018 Dec 16;160:92-109. PMID:30566892
- 18. Karademir B, Sari G, et al. "Proteomic approach for understanding milder neurotoxicity of Carfilzomib against Bortezomib." Sci Rep.2018 Nov 5;8(1):16318. PMID:30397214
- 19. Xiang Y, Wang M, et al. "Mechanisms controlling the multistage post-translational processing of endogenous Nrf1α/TCF11 proteins to yield distinct isoforms within the coupled positive and negative feedback circuits." Toxicol Appl Pharmacol. 2018 Dec 1;360:212-235. PMID:30287392
- 20. Rozic G, Paukov L, et al. "STK405759 as a combination therapy with bortezomib or dexamethasone, in in vitro and in vivo multiple myeloma models." Oncotarget. 2018 Jul 31;9(59):31367-31379. PMID:30140376
- 21. Xinchun Li, Li Zhong, et al. "Phosphorylation of IRS4 by CK1γ2 promotes its degradation by CHIP through the ubiquitin/lysosome pathway." Theranostics, 2018, Vol. 8, Issue13.
- 22. Yuancai Xiang, Josefin Halin, et al."Topovectorial mechanisms control the juxtamembrane proteolytic processing of Nrf1 to remove its N-terminal polypeptides during maturation of the CNC-bZIP factor." bioRxiv.2018. March 27.
- 23. Liew PL, Huang RL, et al. "Distinct methylation profile of mucinous ovarian carcinoma reveals susceptibility to proteasome inhibitors." Int J Cancer. 2018 Feb 16. PMID:29451304
- 24. Yuancai Xiang, et al."Molecular mechanisms controlling the multistage post-translational processing of endogenous Nrf1/TCF11 proteins to yield distinct proteoforms within the coupled positive and negative feedback circuits."bioRxiv.2018. April 12.
- 25. Farris TR, Zhu B, et al. "Ehrlichia chaffeensis TRP32 Nucleomodulin Function and Localization Is Regulated by NEDD4L-Mediated Ubiquitination." Front Cell Infect Microbiol. 2018 Jan 11;7:534. PMID:29376035
- 26. Mañas A, Chen W, et al. "BaxΔ2 sensitizes colorectal cancer cells to proteasome inhibitor-induced cell death." Biochem Biophys Res Commun.2018 Jan 29;496(1):18-24. PMID:29291406
- 27. An H, Harper JW. "Systematic analysis of ribophagy in human cells reveals bystander flux during selective autophagy." Nat Cell Biol. 2017 Dec 11. PMID:29230017
- 28. Chun H, Catterton T, et al. "Organ-specific regulation of ATP7A abundance is coordinated with systemic copper homeostasis." Sci Rep. 2017 Sep 20;7(1):12001. PMID:28931909
- 29. Tian C, Yuan Z, et al. "Inhibition of glycolysis by a novel EGFR/HER2 inhibitor KU004 suppresses the growth of HER2+ cancer." Exp Cell Res. 2017 May 19. pii: S0014-4827(17)30297-5. PMID:28532652
- 30. Lai, Tsung-Hsuan, et al. "Gold Nanoparticles Compromise TNF-α-Induced Endothelial Cell Adhesion Molecule Expression Through NF-κB and Protein Degradation Pathways and Reduce Neointima Formation in a Rat Carotid Balloon Injury Model." Journal of Biomedical Nanotechnology 12.12 (2016): 2185-2201.
- 31. Rose CM, Isasa M, et al. "Highly Multiplexed Quantitative Mass Spectrometry Analysis of Ubiquitylomes." Cell Syst. 2016 Sep 21. PMID:27667366
- 32. Le Goff X, Chesnel F, et al. "Aggregation dynamics and identification of aggregation-prone mutants of the von Hippel-Lindau tumor suppressor protein." J Cell Sci. 2016 Jul 1;129(13):2638-50. PMID:27179072
- 33. Lee BH, Lu Y, et al. "USP14 deubiquitinates proteasome-bound substrates that are ubiquitinated at multiple sites." Nature. 2016 Apr 21;532(7599):398-401 PMID:27074503
- 34. Moriwaki K, Chan FK. "Regulation of RIPK3- and RHIM-dependent Necroptosis by the Proteasome." J Biol Chem. 2016 Mar 11;291(11):5948-59. PMID:26786097
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 384.24 |
Cas No. | 179324-69-7 |
Formula | C19H25BN4O4 |
Synonyms | Bortezomib,PS-341,LDP-341,MLM341,MG-341,NSC-681239 |
Solubility | insoluble in EtOH; insoluble in H2O; ≥19.21 mg/mL in DMSO |
Chemical Name | [(1R)-3-methyl-1-[[(2S)-3-phenyl-2-(pyrazine-2-carbonylamino)propanoyl]amino]butyl]boronic acid |
SDF | Download SDF |
Canonical SMILES | B(C(CC(C)C)NC(=O)C(CC1=CC=CC=C1)NC(=O)C2=NC=CN=C2)(O)O |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验[1]: | |
细胞系 |
犬恶性黑色素瘤细胞系(CMM-1、CMM-2、ChMC、KMeC、LMeC、OMJ、OMS、OMK和NML) |
溶解方法 |
在DMSO中的溶解度>10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。 |
反应条件 |
72 h;IC50=3.5~5.6 nM |
应用 |
Bortezomib有效抑制细胞生长,而其它化合物对细胞生长没有或有很小的影响。在9个犬恶性黑色素瘤细胞系(CMM-1、CMM-2、ChMC、KMeC、LMeC、OMJ、OMS、OMK和NML)中,bortezomib抑制所有细胞系的生长,IC50范围介于3.5~5.6 nM之间。 |
动物实验[1]: | |
动物模型 |
无胸腺裸鼠 |
剂量 |
0.8 mg/kg;静脉注射 |
应用 |
在异种移植小鼠模型中评估bortezomib对CMM-1细胞的体内生长抑制活性。在第4天的治疗后,bortezomib显著抑制肿瘤生长(P < 0.01,对照vs. Bortezomib)。与对照相比,bortezomib治疗小鼠的肿瘤具有显著降低的有丝分裂指数(P |
注意事项 |
请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。 |
References: [1] Ito K, Kobayashi M, Kuroki S, et al. The proteasome inhibitor bortezomib inhibits the growth of canine malignant melanoma cells in vitro and in vivo[J]. The Veterinary Journal, 2013, 198(3): 577-582. |
描述 | Bortezomib (PS-341)是一个有效的20s蛋白酶体抑制剂,Ki值为0.6 nM。 | |||||
靶点 | 20S proteasome | |||||
IC50 | 0.6 nM (Ki) |
质量控制和MSDS
- 批次: