Harringtonine

An inhibitor of translation

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货号: ajci14472
CAS: 26833-85-2
别名: 三尖杉脂碱
分子式: C28H37NO9
分子量: 531.6
纯度: >98%
溶解度: ≤25mg/ml in ethanol;25mg/ml in DMSO;25mg/ml in dimethyl formamide
储存: Store at -20°C
库存: 现货

Background

Harringtonine is a protein synthesis inhibitor [1].

Harringtonine, homoharringtonine and isoharringtonine are alkaloids from Cephalotaxus harringtonia. They have an antitumour activity due to their inhibitory effect on protein synthesis and differ only in a side chain [1].

Harringtonine is a natural alkaloid from Cephalotaxus harringtonia that inhibits protein synthesis in eukaryotic cells. Harringtonine inhibit the initiation of polypeptide synthesis. Harringtonine blocks peptide bond formation and aminoacyl-tRNA binding [1][2]. Harringtonine also immobilizes ribosomes immediately after translation initiation, which can be used to capture ribosome-protected mRNA fragments for evaluating translation [2]. The homolog of harringtonine, homoharrington inhibited the first steps of elongation and rapidly degraded short-lived proteins. In Pten+/- Eμ-Myc lymphomas, homoharrington blocked translation and reduced levels of Mcl-1, Cyclin D1, and c-Myc.

In mice with BCR-ABL-induced CML, homoharrington (also known as omacetaxine) significantly reduced the numbers of both LSCs and total leukemia cells [3][4].

参考文献:
[1].? Fresno M, Jiménez A, Vázquez D. Inhibition of translation in eukaryotic systems by harringtonine. Eur J Biochem. 1977 Jan;72(2):323-30.
[2].? Ingolia NT, Brar GA, Rouskin S, et al. The ribosome profiling strategy for monitoring translation in vivo by deep sequencing of ribosome-protected mRNA fragments. Nat Protoc. 2012 Jul 26;7(8):1534-50.
[3].? Kantarjian HM, O'Brien S, Anderlini P, et al. Treatment of myelogenous leukemia: current status and investigational options. Blood. 1996 Apr 15;87(8):3069-81.
[4].? Chen Y, Peng C, Sullivan C, et al. Novel therapeutic agents against cancer stem cells of chronic myeloid leukemia. Anticancer Agents Med Chem. 2010 Feb;10(2):111-5.

Protocol

Cell experiment:

For harringtonine treatment studies with Sindbis virus, BHK21 cells are seeded into 96-well plates and infected with Sindbis virus at an MOI of 1 for 1 h prior to being washed twice with PBS and incubated with various concentrations of harringtonine (0.1 μM, 1 μM, 5 μM, and 10 μM) at 37°C with 5% CO2. Cell supernatants are harvested for plaque assays at 24 h postinfection[2].

参考文献:

[1]. Fresno M, et al. Inhibition of translation in eukaryotic systems by harringtonine. Eur J Biochem. 1977 Jan;72(2):323-30.
[2]. Kaur P, et al. Inhibition of chikungunya virus replication by harringtonine, a novel antiviral that suppresses viral protein expression. Antimicrob Agents Chemother. 2013 Jan;57(1):155-67.
[3]. Piao YF, et al. Growth inhibition of human myeloid leukemia cells in vitro by harringtonine. Gan To Kagaku Ryoho. 1990 Feb;17(2):281-5.