Emetine (hydrochloride)

Emetine (dihydrochloride) is an anti-protozoal drug previously used for intestinal and tissue amoebiasis[1].

Emetine dihydrochloride is reported to have an IC50 value of 1 nM on the drug sensitive 3D7 P. falciparum parasite strains. Dose response curves are determined for both drugs using K1 resistant isolates and IC50 values of 47 nM and 2.6 nM established for emetine dihydrochloride hydrate and DHA, respectively[1]. After the lymphoblasts are treated with emetine dihydrochloride, the expression level of the mutant allele is elevated almost equally to the wild-type alleles by direct sequencing of the corresponding cDNA[2]. Emetine dihydrochloride is identified as a lead compound with significant concentration dependent suppression of PEDF-induced TNF secretion and an IC50 of 146 nM. Emetine dihydrochloride inhibits PEDF-mediated TNF release without affecting cell viability and binds to PEDF receptor ATGL with high-binding affinity (KD=14.3 nM)[3].Emetine dihydrochloride reduces cell viability, induces apoptosis, promptes AML cells towards differentiation and downregulates HIF-1α[4].

Emetine dihydrochloride (0.002, 0.02, 0.2 and 2 mg/kg) not only attenuates blood glucose levels in dose-dependent way but also induces a persistent attenuation of blood glucose levels. Daily administration of emetine dihydrochloride dose-dependently attenuates hyperglycemic response by d 21. Consistent with this observation, administration of emetine dihydrochloride, but not the vehicle control, results in a sustained attenuation of blood glucose levels. Emetine dihydrochloride improves disease severity in a spontaneous model of NOD T1D[3]. Emetine dihydrochloride (1 mg/kg) reduces both leukemia burden in an in vivo xenotransplantation mouse model and the clonogenic capacity of leukemic cells upon treatment[4].

References:
[1]. Matthews H, et al. Drug repositioning as a route to anti-malarial drug discovery: preliminary investigation of the in vitro anti-malarial efficacy of emetine dihydrochloride hydrate. Malar J. 2013 Oct 9;12:359.
[2]. Wu L, et al. PRRT2 truncated mutations lead to nonsense-mediated mRNA decay in Paroxysmal Kinesigenic Dyskinesia. Parkinsonism Relat Disord. 2014 Dec;20(12):1399-404
[3]. Hudson LK, et al. Emetine Di-HCl attenuates Type 1 diabetes mellitus in mice. Mol Med. 2016 Jun 10;22
[4]. Cornet-Masana JM, et al. Emetine induces chemosensitivity and reduces clonogenicity of acute myeloid leukemia cells. Oncotarget. 2016 Apr 26;7(17):23239-50