Nachliely, Matan; Trachtenberg, Aviram; Khalfin, Boris; Nalbandyan, Karen; Cohen-Lahav, Merav; Yasuda, Kaori; Sakaki, Toshiyuki; Kutner, Andrzej; Danilenko, Michael published the artcile< Dimethyl fumarate and vitamin D derivatives cooperatively enhance VDR and Nrf2 signaling in differentiating AML cells in vitro and inhibit leukemia progression in a xenograft mouse model>, Recommanded Product: (9Z,12Z)-Methyl octadeca-9,12-dienoate, the main research area is acute myeloid leukemia inhibition dimethyl fumarate VDR Nrf2 signaling; 25-dihydroxyvitamin D(2); Acute myeloid leukemia; Analogs of 1; Cell differentiation; Dimethyl fumarate; PRI-5202; Paricalcitol (PRI-5100); Resistance to CYP24A1-mediated metabolism; Vitamin D receptor; Xenograft mouse model of AML.
Here, we demonstrate that in AML cell cultures, moderate pro-differentiation effects of low concentrations of VDDs can be synergistically enhanced by structurally distinct compounds known to activate the transcription factor Nuclear Factor (Erythroid-derived 2)-Like 2 (NFE2L2 or Nrf2). Particularly, di-Me fumarate (DMF), which is clin. approved for the treatment of multiple sclerosis and psoriasis, strongly cooperated with 1,25D3, PRI-5100 (19-nor-1,25D2; paricalcitol) and PRI-5202 (a double-point modified 19-nor analog of 1,25D2). These data support the notion that VDDs and Nrf2 activators synergize in inducing myeloid cell differentiation through the cooperative activation of the VDR and Nrf2/antioxidant response element signaling pathways. We have previously reported that PRI-5202 is more potent by approx. two orders of magnitude than 1,25D3 as a differentiation inducer in AML cell lines. In addition, PRI-5202 was remarkably more resistant against degradation by the human 25-hydroxyvitamin D3-24-hydroxylase than both 1,25D2 and 1,25D3. Importantly, using a xenograft mouse model we demonstrated that co-administration of PRI-5202 and DMF resulted in a marked cooperative inhibition of human AML tumor growth without inducing treatment toxicity. Collectively, our findings provide a rationale for clin. testing of low-toxic VDD/DMF combinations as a novel approach for differentiation therapy of AML.
Journal of Steroid Biochemistry and Molecular Biology published new progress about Acute myeloid leukemia. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Recommanded Product: (9Z,12Z)-Methyl octadeca-9,12-dienoate.
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