Emetine dihydrochloride hydrate is an antigen parasite drug that can be used for the treatment of intestinal and tissue amoebic diseases[1].
Emetine dihydrochloride is reported to have an IC50 value of 1nM 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 47nM and 2.6nM established for Emetine dihydrochloride hydrate and DHA, respectively[1]. After the lymphoblasts are treated with Emetine dihydrochloride hydrate, 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 hydrate is identified as a lead compound with significant concentration dependent suppression of PEDF-induced TNF secretion and an IC50 of 146nM. Emetine dihydrochloride hydrate inhibits PEDF-mediated TNF release without affecting cell viability and binds to PEDF receptor ATGL with high-binding affinity (Kd=14.3nM)[3]. Emetine dihydrochloride hydrate reduces cell viability, induces apoptosis, promptes AML cells towards differentiation and downregulates HIF-1α[4].
Emetine dihydrochloride hydrate (0.002, 0.02, 0.2 and 2mg/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 hydrate dose-dependently attenuates hyperglycemic response by D21. Consistent with this observation, administration of Emetine dihydrochloride hydrate, but not the vehicle control, results in a sustained attenuation of blood glucose levels. Emetine dihydrochloride hydrate improves disease severity in a spontaneous model of NOD T1D[3]. Emetine dihydrochloride hydrate (1mg/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.
Emetine dihydrochloride hydrate是一种抗原虫药物，能够用于肠和组织阿米巴病的治疗[1]。
据报道，Emetine dihydrochloride对3D7型恶性疟原虫药敏株的IC50值为1nM。采用K1耐药菌株确定了两种药物的剂量反应曲线，并分别建立了Emetine dihydrochloride hydrate和DHA的IC50值为47nM和2.6nM。用Emetine dihydrochloride hydrate处理淋巴母细胞后，通过对相应cDNA的直接测序，突变等位基因的表达水平几乎与野生型等位基因相同[2]。Emetine dihydrochloride hydrate是一种先导化合物，对PEDF诱导的TNF分泌具有明显的浓度依赖性抑制作用，IC50为146nM。Emetine dihydrochloride hydrate抑制PEDF介导的TNF释放而不影响细胞活力，并以高结合亲和力（Kd=14.3nM）与PEDF受体ATGL结合[3]。Emetine dihydrochloride hydrate降低细胞活力，诱导细胞凋亡，促进AML细胞分化，下调HIF-1α[4]。
Emetine dihydrochloride hydrate（0.002、0.02、0.2和2mg/kg）不仅呈剂量依赖性地降低血糖水平，而且能诱导血糖水平持续降低。每日给予Emetine dihydrochloride hydrate剂量依赖性降低高血糖反应至21d。与这一观察结果一致，给予Emetine dihydrochloride hydrate，而不是对照，导致血糖水平持续下降。Emetine dihydrochloride hydrate改善NOD T1D自发性模型的疾病严重程度[3]。Emetine dihydrochloride hydrate（1mg/kg）可降低体内异种移植小鼠模型的白血病负担和治疗后白血病细胞的克隆生成能力[4]。