Vithya Manoharan

TL;DR: A novel potent, orally available PORCN inhibitor, ETC-1922159, that blocks the secretion and activity of all Wnts is developed that is remarkably effective in treating RSPO-translocation bearing colorectal cancer patient-derived xenografts.

TL;DR: The identification of a Wnt secretion inhibitor from cellular high throughput screening is described and it is discovered that enantiomeric PORCN inhibitors show very different activity in the reporter assay, suggesting that such compounds may be useful for mode of action studies on the POR CN O-acyltransferase.

TL;DR: The structure-activity relationships and pharmacokinetic properties of a selective MNK1/2 inhibitor clinical candidate, ETC-206, which in combination with dasatinib prevents BC-CML LSC self-renewal in vitro and enhances d asatinib antitumor activity in vivo are reported.

TL;DR: The identification of novel dual MNK1 and 2 and BCR-ABL1 inhibitors, starting from the known kinase inhibitor 2, which are efficacious in a mouse xenograft model and reduce the level of phosphorylated eukaryotic translation initiation factor 4E in the tumor tissues.

TL;DR: A pharmacophore model was developed and used the putative bioactive conformation of a xanthine inhibitor for scaffold hopping and the resulting maleimide scaffold was optimized to subnanomolar potency while retaining good physical druglike properties.