Carfilzomib (PR-171)
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.
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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