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- Carfilzomib (PR-171)
Carfilzomib (PR-171)
An epoxomicin derivate with potential antineoplastic activity. It irreversibly binds to and inhibits the chymotrypsin-like activity of the 20S proteasome, an enzyme responsible for degrading a large variety of cellular proteins. Inhibition of proteasome-mediated proteolysis results in an accumulation of polyubiquinated proteins, which may lead to cell cycle arrest, induction of apoptosis, and inhibition of tumor growth.
References:
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 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
HT-29 colorectal adenocarcinoma cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
1 h; IC50=9 nM |
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Applications |
Incubation of HT-29 colorectal adenocarcinoma cells with PR-171 for 1 h resulted in a dose-dependent inhibition of all three proteasome catalytic activities with the chymotrypsin-like activity exhibiting the greatest sensitivity (IC50=9 nM). The caspase-like and trypsin-like activities were inhibited to a greater extent in the cellular assay (IC50=150-200 nM) than in the isolated enzyme assay (IC50 >1 μM). |
| Animal experiment [1]: | |
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Animal models |
BNX mice |
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Dosage form |
5 mg/kg delivered weekly; QDx2; intravenous injection |
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Applications |
The antitumor activity of PR-171 was evaluated in BNX mice bearing established human tumor xenografts derived from three tumor cell lines: HT-29 (colorectal adenocarcinoma), RL (B cell lymphoma ), and HS-Sultan (Burkitt’s lymphoma). All PR-171 dosing schedules (up to 5 mg/kg delivered weekly QDx2) were tolerated in the tumor-bearing animals, resulting in weight loss of |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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. |
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| Description | Carfilzomib (PR-171) is an irreversible inhibitor of proteasome with IC50 of <5 nM. | |||||
| Targets | Proteasome | |||||
| IC50 | 5 nM | |||||
Quality Control & MSDS
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