Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer

Qing Dong; Douglas R Dougan; Xianchang Gong; Petro Halkowycz; Bohan Jin; Toufike Kanouni; Shawn M O'Connell; Nicholas Scorah; Lihong Shi; Michael B Wallace; Feng Zhou

doi:10.1016/j.bmcl.2011.01.071

Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer

Bioorg Med Chem Lett. 2011 Mar 1;21(5):1315-9. doi: 10.1016/j.bmcl.2011.01.071. Epub 2011 Jan 22.

Authors

Qing Dong¹, Douglas R Dougan, Xianchang Gong, Petro Halkowycz, Bohan Jin, Toufike Kanouni, Shawn M O'Connell, Nicholas Scorah, Lihong Shi, Michael B Wallace, Feng Zhou

Affiliation

¹ Takeda San Diego, San Diego, CA 92121, USA.

PMID: 21310613
DOI: 10.1016/j.bmcl.2011.01.071

Abstract

A novel 5-phenylamino-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione series of MEK inhibitors has been developed using structure-based drug design. Lead optimization of this series led to the discovery of TAK-733. This was advanced to Phase I clinical studies for cancer treatment.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Binding Sites
Crystallography, X-Ray
Drug Discovery*
Humans
MAP Kinase Kinase Kinases / antagonists & inhibitors*
Models, Molecular
Molecular Structure
Neoplasms / drug therapy*
Pyridones / chemical synthesis
Pyridones / chemistry
Pyridones / therapeutic use*
Pyrimidinones / chemical synthesis
Pyrimidinones / chemistry
Pyrimidinones / therapeutic use*

Substances

Antineoplastic Agents
Pyridones
Pyrimidinones
TAK 733
MAP Kinase Kinase Kinases