Homoharringtonine

Homoharringtonine is an alkaloid originally isolated from C. harringtonia and a homolog of harringtonine (Cay-15361) that has diverse biological activities including protein synthesis inhibitory, antiviral, antiparasitic, and anticancer properties. Homoharringtonine inhibits the chain elongation phase of translation in eukaryotes. It inhibits diphenylalanine formation by rabbit reticulocyte and human placental ribosomes in cell-free assays and binds to human 80S ribosomes (Kd = 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. 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). It also inhibits the growth of P. falciparum in cultured in human erythrocytes (IC50 = 4 nM). 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). 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. 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.Formal Name: 3-[4-methyl (2R)-2-hydroxy-2-(4-hydroxy-4-methylpentyl)butanedioate]cephalotaxine. CAS Number: 26833-87-4. Synonyms: NSC 141633, Omacetaxine Mepesuccinate. Molecular Formula: C29H39NO9. Formula Weight: 545.6. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMSO: 50 mg/ml, Ethanol: 25 mg/ml. SMILES: O=C(OC)C[C@@](CCCC(C)(O)C)(O)C(O[C@H]1[C@](C(C=C(OCO2)C2=C3)=C3CCN4CCC5)([H])[C@]45C=C1OC)=O. InChi Code: InChI=1S/C29H39NO9/c1-27(2,33)8-5-10-29(34,16-23(31)36-4)26(32)39-25-22(35-3)15-28-9-6-11-30(28)12-7-18-13-20-21(38-17-37-20)14-19(18)24(25)28/h13-15,24-25,33-34H,5-12,16-17H2,1-4H3/t24-,25-,28+,29-/m1/s1. InChi Key: HYFHYPWGAURHIV-JFIAXGOJSA-N. Origin: Plant/Cedar bark.