Homoharringtonine

Homoharringtonine is an alkaloid originally isolated from C. harringtonia and a homolog of harringtonine (Item No. 15361) that has diverse biological activities including protein synthesis inhibitory, antiviral, antiparasitic, and anticancer properties.¹ Homoharringtonine inhibits the chain elongation phase of translation in eukaryotes.² It inhibits diphenylalanine formation by rabbit reticulocyte and human placental ribosomes in cell-free assays and binds to human 80S ribosomes (K_d = 39 nM). Homoharringtonine is active against coronaviruses, reducing the viral load in vitro and in vivo and prevents severe symptoms in porcine and chicken models of porcine epidemic diarrhea virus (PEDV) and Newcastle disease virus (NDV), respectively.³ It reduces the infectious virus yield and viral RNA copy numbers in the culture supernatant of Vero E6 cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (EC₅₀s = 2.55 and 2.14 µM, respectively).⁴ It also inhibits the growth of P. falciparum in cultured in human erythrocytes (IC₅₀ = 4 nM).⁵ Homoharringtonine is cytotoxic and inhibits the proliferation of Jurkat acute T cell leukemia (IC₅₀ = 9 nM) and K562 chronic myelogenous leukemia (CML) cells (IC₅₀ = 408 μg/ml).^6,7 In vivo, it decreases the number of peripheral leukemia stem cells and increases survival in CML and B cell acute lymphoblastic leukemia (B-ALL) mouse models when administered at a dose of 0.5 mg/kg.⁸ Formulations containing homoharringtonine have been used in the treatment of CML in patients with resistance and/or intolerance to two or more tyrosine kinase inhibitors.

WARNING This product is not for human or veterinary use.

1. Powell, R.G., Wesileder, D., Smith, C.R., Jr., et al. Structures of harringtonine, isoharringtonine, and homoharringtonine. Tetrahedron Lett. 11(11), 815-818 (1970).

2. Tujebajeva, R.M., Graifer, D.M., Matasova, N.B., et al. Selective inhibition of the polypeptide chain elongation in eukaryotic cells. Biochim. Biophys. Acta 1129(2), 177-182 (1992).

3. Dong, H.-J., Wang, Z.-H., Meng, W., et al. The natural compound homoharringtonine presents broad antiviral activity in vitro and in vivo. Viruses 10(11), 601 (2018).

4. Choy, K.-T., Wong, A.-Y., Kaewpreedee, P., et al. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Res. 178, 104786 (2020).

5. Ekong, R.M., Kirby, G.C., Patel, G., et al. Comparison of the in vitro activities of quassinoids with activity against Plasmodium falciparum, anisomycin and some other inhibitors of eukaryotic protein synthesis. Biochem. Pharmacol. 40(2), 297-301 (1990).

6. Efferth, T., Sauerbrey, A., Halatsch, M.E., et al. Molecular modes of action of cephalotaxine and homoharringtonine from the coniferous tree Cephalotaxus hainanensis in human tumor cell lines. Naunyn Schmiedebergs Arch. Pharmacol. 367(1), 56-67 (2003).

7. Moirangthem, D.S., Borah, J.C., Laishram, S., et al. HPLC analysis of harringtonine and homoharringtonine in the needles of Cephalotaxus griffithii alkaloid fraction and cytotoxic activity on chronic myelogenous leukaemia K562 cell. Nat. Prod. Res. 28(18), 1503-1506 (2014).

8. Chen, Y., Hu, Y., Michaels, S., et al. Inhibitory effects of omacetaxine on leukemic stem cells and BCR-ABL-induced chronic myeloid leukemia and acute lymphoblastic leukemia in mice. Leukemia 23(8), 1446-1454 (2009).