Carfilzomib (PR-171)
![mRNA synthesis](/media/diy/images/page/figure1-mrna.png)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
![Tyramine Signal Amplification (TSA)](/media/diy/images/page/figure2-01.png)
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
![screening library](/media/diy/images/page/figure3-01.png)
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
![Cell Counting Kit-8 (CCK-8)](/media/diy/images/page/CCK-8.jpg)
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
![SYBR Safe DNA Gel Stain](/media/diy/images/page/SYBR Safe DNA Gel Stain.png)
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
![Inhibitor Cocktails](/media/diy/images/page/Inhibitor Cocktails.jpg)
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Carfilzomib (PR-171)是环氧酶素(epoxomicin)的衍生物,具有潜在的抗肿瘤活性。Carfilzomib不可逆的结合并抑制20S蛋白酶体的胰凝乳蛋白酶样活性。20S蛋白酶体负责降解大量的细胞内蛋白。抑制蛋白酶体介导的蛋白水解可以引起聚泛素化蛋白的积累,从而导致细胞周期停滞、诱导细胞凋亡和抑制肿瘤生长[1]。
参考文献:
[1]. Guido Cavaletti, et al., Leukemia & Lymphoma (2010), 51(7), 1178-1187. 2. Girija Dasmahapatra, et al., Blood (2010), 115(22), 4478-4487.
- 1. Chunyan Gu, Yajun Wang, et al. "AHSA1 is a promising therapeutic target for cellular proliferation and proteasome inhibitor resistance in multiple myeloma." J Exp Clin Cancer Res. 2022 Jan 6;41(1):11. PMID: 34991674
- 2. Hongo A, Kanaseki T, et al. "Upstream Position of Proline Defines Peptide-HLA Class I Repertoire Formation and CD8(+) T Cell Responses." J Immunol. 2019 May 15; 202 (10): 2849-2855. PMID: 30936292
- 3. 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.
- 4. 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
- 5. Uddin MM, Zou Y, et al. "Proteasome inhibition induces IKK-dependent interleukin-8 expression in triple negative breast cancer cells: Opportunity for combination therapy." PLoS One. 2018 Aug 8; 13 (8): e0201858. PMID: 30089134
- 6. Zheng Y, Liu Q, t al. "Zika virus elicits inflammation to evade antiviral response by cleaving cGAS via NS1-caspase-1 axis." EMBO J. 2018 Jul 31. pii: e99347. PMID: 30065070
- 7. 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
- 8. 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
- 9. Ma?as 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
- 10. Yamashita Y, Anczurowski M, et al."HLA-DP(84Gly) constitutively presents endogenous peptides generated by the class I antigen processing pathway." Nat Commun. 2017 May 10; 8: 15244. PMID: 28489076
- 11. Federspiel JD, Codreanu SG, et al. "Specificity of protein covalent modification by the electrophilic proteasome inhibitor carfilzomib in human cells." Mol Cell PMID: 27503896
Physical Appearance | A solid |
Storage | Desiccate at -20°C |
M.Wt | 719.91 |
Cas No. | 868540-17-4 |
Formula | C40H57N5O7 |
Synonyms | PR 171,PR171,PR-171,Carfilzomib |
Solubility | ≥35.99 mg/mL in DMSO; insoluble in H2O; ≥2.64 mg/mL in EtOH with gentle warming and ultrasonic |
Chemical Name | (2S)-4-methyl-N-[(2S)-1-[[(2S)-4-methyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]-4-phenylbutanoyl]amino]pentanamide |
SDF | Download SDF |
Canonical SMILES | CC(C)CC(C(=O)C1(CO1)C)NC(=O)C(CC2=CC=CC=C2)NC(=O)C(CC(C)C)NC(=O)C(CCC3=CC=CC=C3)NC(=O)CN4CCOCC4 |
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 |
HT-29结肠腺癌细胞 |
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 |
1 h;IC50 = 9 nM |
应用 |
HT-29结肠腺癌细胞与PR-171孵育1 h可导致所有三个蛋白酶体催化活性的剂量依赖性抑制,其中胰凝乳蛋白酶样活性具有最大的敏感性(IC50 = 9 nM)。与分离酶实验相比(IC50>1 μM),细胞实验中caspase样和胰蛋白酶样活性可以更大程度地被抑制(IC50=150–200 nM)。 |
动物实验[1]: | |
动物模型 |
BNX小鼠 |
剂量 |
5 mg/kg/周,连续两天(QDx2);静脉注射 |
应用 |
在人肿瘤异种移植BNX小鼠中评估PR-171的抗肿瘤活性,异种移植物源自三个肿瘤细胞系,分别是HT-29(结肠腺癌)、RL(B细胞淋巴瘤)和HS-Sultan(伯基特氏淋巴瘤)。所有的PR-171给药方案(高达5 mg/kg,QDx2)在荷瘤动物中均具有耐受性,体重下降小于10%。结果表明,PR-171的活性是剂量和给药方案依赖的。PR-171也可以抑制血液和肾上腺中蛋白酶体的活性。 |
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] Demo S D, Kirk C J, Aujay M A, et al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome[J]. Cancer research, 2007, 67(13): 6383-6391. |
描述 | Carfilzomib (PR-171)是一种不可逆的蛋白酶体抑制剂,IC50 < 5 nM。 | |||||
靶点 | Proteasome | |||||
IC50 | 5 nM |
质量控制和MSDS
- 批次:
化学结构
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