title: Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer.
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.
authors.affiliation: Takeda San Diego, San Diego, CA 92121, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Dong
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Dougan
authors.forename: Xianchang
authors.initials: X
authors.lastname: Gong
authors.forename: Petro
authors.initials: P
authors.lastname: Halkowycz
authors.forename: Bohan
authors.initials: B
authors.lastname: Jin
authors.forename: Toufike
authors.initials: T
authors.lastname: Kanouni
authors.forename: Shawn M
authors.initials: SM
authors.lastname: O'Connell
authors.forename: Nicholas
authors.initials: N
authors.lastname: Scorah
authors.forename: Lihong
authors.initials: L
authors.lastname: Shi
authors.forename: Michael B
authors.initials: MB
authors.lastname: Wallace
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001665:Binding Sites; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D011728:Pyridones; D011744:Pyrimidinones; C558666:TAK 733; D020930:MAP Kinase Kinase Kinases