Prakash, Muthuraj; Itoh, Yukihiro; Fujiwara, Yoshie; Takahashi, Yukari; Takada, Yuri; Mellini, Paolo; Elboray, Elghareeb E.; Terao, Mitsuhiro; Yamashita, Yasunobu; Yamamoto, Chika; Yamaguchi, Takao; Kotoku, Masayuki; Kitao, Yuki; Singh, Ritesh; Roy, Rohini; Obika, Satoshi; Oba, Makoto; Wang, Dan Ohtan; Suzuki, Takayoshi published the artcile< Identification of Potent and Selective Inhibitors of Fat Mass Obesity-Associated Protein Using a Fragment-Merging Approach>, Reference of 329214-79-1, the main research area is fat mass obesity associated protein inhibitor preparation cancer.
Fat mass obesity-associated protein (FTO) is a DNA/RNA demethylase involved in the epigenetic regulation of various genes and is considered a therapeutic target for obesity, cancer, and neurol. disorders. Here, we aimed to design novel FTO-selective inhibitors by merging fragments of previously reported FTO inhibitors. Among the synthesized analogs, compound 11b, which merges key fragments of Hz (3) and MA (4), inhibited FTO selectively over alkylation repair homolog 5 (ALKBH5), another DNA/RNA demethylase. Treatment of acute monocytic leukemia NOMO-1 cells with a prodrug of 11b decreased the viability of acute monocytic leukemia cells, increased the level of the FTO substrate N6-methyladenosine in mRNA, and induced upregulation of MYC and downregulation of RARA, which are FTO target genes. Thus, Hz (3)/MA (4) hybrid analogs represent an entry into a new class of FTO-selective inhibitors.
Journal of Medicinal Chemistry published new progress about Acute monocytic leukemia. 329214-79-1 belongs to class pyridine-derivatives, and the molecular formula is C11H16BNO2, Reference of 329214-79-1.