Chemical Properties
Off-White to Pale Beige Solid
Uses
An inhibitor of ERK signaling pathway. A MAP kinase inhibitor. Potent MEK inhibitor.
Definition
ChEBI: 2-(2-chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide is an aminobenzoic acid.
Biological Activity
pd184352 (also known as ci-1040), a benzhydroxamate derivative, is a potent and highly selective mek1/2, two members of the family of mapkks, inhibitor that inhibits purified mek1 with ic50 of 17 nm in a non-atp and non-erk1/2 competitive manner [1].pd184352 binds to a hydrophobic pocket, which is located in a region with low sequence homology to other kinases, adjacent to the mg-atp binding site of mek1 and mek2 inducing a conformational change in un-phosphorylated mek1/2 and hence inactivating the un-phosphorylated mek1/2 [1].pd184352 has been found to be actively against tumors, where it inhibits the growth of colon carcinomas in mouse xenograft models [1].
Biochem/physiol Actions
PD184352 (CI-1040) is a highly selective non-competitive inhibitor of MEK (MKK1; MAPK kinase) and the closely related MKK2. It has anti-cancer activity, suppresses the ERK pathway, and has been used along with other classes of inhibitors to establish embryonic stem cell lines.
References
[1] frémin c, meloche s. from basic research to clinical development of mek1/2 inhibitors for cancer therapy. j hematol oncol. 2010 feb 11;3:8. doi: 10.1186/1756-8722-3-8.
