Related Experiment Video
Updated: Jan 25, 2026

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
Published on: October 5, 2020
Structure-based identification of ureas as novel nicotinamide phosphoribosyltransferase (Nampt) inhibitors
Xiaozhang Zheng1, Paul Bauer, Timm Baumeister
1Forma Therapeutics, Inc., 500 Arsenal Street, Watertown, Massachusetts 02472, USA. xzheng@formatherapeutics.com
Abstract:
Nicotinamide phosphoribosyltransferase (Nampt) is a promising anticancer target. Virtual screening identified a thiourea analogue, compound 5, as a novel highly potent Nampt inhibitor. Guided by the cocrystal structure of 5, SAR exploration revealed that the corresponding urea compound 7 exhibited similar potency with an improved solubility profile. These studies also indicated that a 3-pyridyl group was the preferred substituent at one inhibitor terminus and also identified a urea moiety as the optimal linker to the remainder of the inhibitor structure. Further SAR optimization of the other inhibitor terminus ultimately yielded compound 50 as a urea-containing Nampt inhibitor which exhibited excellent biochemical and cellular potency (enzyme IC50 = 0.007 μM; A2780 IC50 = 0.032 μM). Compound 50 also showed excellent in vivo antitumor efficacy when dosed orally in an A2780 ovarian tumor xenograft model (TGI of 97% was observed on day 17).
Related Concept Videos
Urea Cycle
Eukaryotic Transcription Inhibitors
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Dipeptidyl Peptidase 4 Inhibitors
Structures of Solids
Structural Isomerism
Isomers are different chemical species that have the same chemical formula. Structural isomerism of coordination compounds can be divided into two subcategories, the linkage isomers and coordination-sphere isomers.
Linkage isomers occur when the coordination compound contains a ligand that can bind to the transition metal center through two different atoms. For example, the CN− ligand can bind through the carbon atom or through the nitrogen atom. Similarly, SCN− can...
Structure of Lipids

