生物活性

• 描述Harringtonine (HT) is a naturally occurring alkaloid isolated from the plant genus Cephalotaxus. It possesses antileukemic activity and has been clinically utilized for the treatment of acute leukemia and lymphoma^[2]. Harringtonine possessed anti-ZIKV (Mosquito-borne Zika virus) properties against the binding, entry, replication, and release stage through the virus life cycle. In addition, harringtonine have strong virucidal effects in ZIKV and exhibited prophylaxis antiviral ability prior ZIKV infection^[3]. Harringtonine, a cephalotaxine alkaloid, displayed potent inhibition of CHIKV infection (50% effective concentration [EC(50)] = 0.24 μM) with minimal cytotoxicity and was selected for elucidation of its antiviral mechanism^[4]. Up-regulation of TrpRS, RS, prohibitin and down-regulation of BTF3 were involved in inhibition of transcription and protein synthesis in the apoptotic K562 cells induced by HT(harringtonine), whereas up-regulation of keratin 9 was related to apoptosis resistance^[5].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02029417	Acute Myeloid Leukemia With Mu... more >>ltilineage Dysplasia Following Myelodysplastic Syndrome Adult Acute Megakaryoblastic Leukemia (M7) Adult Acute Minimally Differentiated Myeloid Leukemia (M0) Adult Acute Monoblastic Leukemia (M5a) Adult Acute Monocytic Leukemia (M5b) Adult Acute Myeloblastic Leukemia With Maturation (M2) Adult Acute Myeloblastic Leukemia Without Maturation (M1) Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Acute Myelomonocytic Leukemia (M4) Adult Erythroleukemia (M6a) Adult Pure Erythroid Leukemia (M6b) Secondary Acute Myeloid Leukemia Untreated Adult Acute Myeloid Leukemia Collapse <<	Phase 2	Terminated(Major revisions nee... more >>ded in study) Collapse <<	-	United States, New York ... more >> Roswell Park Cancer Institute Buffalo, New York, United States, 14263 Collapse <<
  NCT02029417	-	-	Terminated(Major revisions nee... more >>ded in study) Collapse <<	-	-
  NCT03170895	AML FLT3-ITD ... more >>Mutation Collapse <<	Phase 2	Recruiting	October 1, 2021	Hong Kong ... more >> The University of Hong Kong Recruiting Hong Kong, Hong Kong Contact: Chunxiao Zhang, SC    852-22554361    chunxiao@hku.hk Collapse <<

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• 参考文献

• [1] Fang M, Zhang H, et al. Intracellular calcium distribution in apoptosis of HL-60 cells induced by harringtonine: intranuclear accumulation and regionalization. Cancer Lett. 1998 May 15;127(1-2):113-21.

  [2] Sakamoto S, Miyamoto T, Usui K, Tanaka H, Morimoto S. Sodium-Periodate-Mediated Harringtonine Derivatives and Their Antiproliferative Activity against HL-60 Acute Leukemia Cells. J Nat Prod. 2018 Jan 26;81(1):34-40

  [3] Lai ZZ, Ho YJ, Lu JW. Harringtonine Inhibits Zika Virus Infection through Multiple Mechanisms. Molecules. 2020 Sep 7;25(18):4082

  [4] Kaur P, Thiruchelvan M, Lee RC, Chen H, Chen KC, Ng ML, Chu JJ. Inhibition of chikungunya virus replication by harringtonine, a novel antiviral that suppresses viral protein expression. Antimicrob Agents Chemother. 2013 Jan;57(1):155-67

  [5] Li R, Liu XL, Du QF, Zhang S, Luo RC, Zhou SY. [Proteome analysis of apoptotic K562 cells induced by harringtonine]. Zhonghua Xue Ye Xue Za Zhi. 2004 Jun;25(6):323-7. Chinese

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