Development of 3-arylaminothiophenic-2-carboxylic acid derivatives as new FTO inhibitors showing potent antileukemia activities.

Fat mass and obesity-associated protein (FTO) is the first discovered RNA N-methyladenosine (mA) demethylase. The highly expressed FTO protein is required to trigger oncogenic pathways in acute myeloid leukemia (AML), which makes FTO a promising antileukemia drug target. In this study, we identify 3-arylaminothiophenic-2-carboxylic acid derivatives as new FTO inhibitors with good antileukemia activity.

Rational Design of RNA Demethylase FTO Inhibitors with Enhanced Antileukemia Drug-Like Properties.

The fat mass and obesity-associated protein (FTO) is an RNA -methyladenosine (mA) demethylase highly expressed in diverse cancers including acute myeloid leukemia (AML). To improve antileukemia drug-like properties, we have designed /ZLD115, a flexible alkaline side-chain-substituted benzoic acid FTO inhibitor derived from FB23. A combination of structure-activity relationship analysis and lipophilic efficiency-guided optimization demonstrates that /ZLD115 exhibits better drug-likeness than the previously reported FTO inhibitors, FB23 and /Dac85.

Structure-Activity Relationships and Antileukemia Effects of the Tricyclic Benzoic Acid FTO Inhibitors.

The -methyladenosine (mA) demethylase FTO is overexpressed in acute myeloid leukemia (AML) cells and promotes leukemogenesis. We previously developed tricyclic benzoic acid FB23 as a highly potent FTO inhibitor in vitro. However, it showed a moderate antiproliferative effect on AML cells.

Differential expression profiling and functional analysis of microRNAs through stage I-III papillary thyroid carcinoma.

Objective: To elucidate the mechanisms undergoing the pathogenesis of PTC, this study try to find stage specific microRNAs (miRNAs) using microarray chip in stage I, II and III papillary thyroid carcinoma (PTC) tissues as well predict miRNAs binding target genes and their molecular functions.

Methods: PTC specimens of stage I, II, and III and their paired adjacent non-tumor tissue (one patient for each stage) were collected. The expressions of miRNAs were examined using miRNA microarray chip.

Design, synthesis, and insecticidal activities of novel monohalovinylated pyrethroids.

A series of novel monohalovinylated pyrethroids are designed and synthesized to replace one halo atom with a hydrogen atom on the double bond of dihalopyrethroids. Bioassays indicate that some of the synthesized compounds, such as 3j and 1j, exhibit high insecticidal activities against mosquitoes ( Culex pipiens pallens ), oriental armyworms ( Mythimna separata ), alfalfa aphids ( Aphis medicagini ), and carmine spider mites ( Tetranychus cinnabarinus ). Photolytic results of E-cis-1j suggest that monohalovinylated pyrethroids are photodegraded more easily than compound 12.