Chemical Properties
White to Off-White Solid
Usage
The mitogenic extracellular kinase 1/2 (MEK1/2) inhibitor
Description
PD 325901 (391210-10-9) is a selective non-ATP competitive MEK inhibitor (IC50 = 0.33 nM).1 Inhibits growth and/or proliferation of a variety of cancer cells.2 Enhances self-renewal of embryonic stem cells.3 In combination with vitamin C, synergistically induces hypomethylation of mouse embryonic stem cells.4 In combination with CHIR-99021 and A83-01 induces generation of ground state iPS cells from human and rat somatic cells.5
Uses
PD 0325901 has been used as an inhibitor in extracellular signal-regulated kinase (ERK) inhibition assay in primed induced pluripotent stem cells, RKO colorectal cancer cell line and human embryonic stem cells(hESCs).
Uses
The mitogenic extracellular kinase 1/2 (MEK1/2) inhibitor
Definition
ChEBI: A hydroxamic acid ester that is benzhydroxamic acid (N-hydroxybenzamide) in which the hydroxamic acid group has been converted to the corresponding 2,3-dihydroxypropyl ester and in which the benzene ring has been substituted at position
by a (2-fluoro-4-iodophenyl)amino group and at positions 3 and 4 by fluorines (the R enantiomer).
Biochem/physiol Actions
PD 0325901 is a potent MKK1 (MEK1) and MKK2 (MEK2) inhibitor. The Ki is 1.1 and 0.79 nM for MEK1 and MEK2, respectively. PD 0325901 was inactive against a panel of 27 other kinases. PD 0325901 inhibited C26 tumor pERK by 75% when dosed at 25 mg/kg in mice.
References
1) Sebolt-Leopold et al. (2004), The biological profile of PD0325901: A second generation analog of CI-1040 with improved pharmaceutical potential; Proc. Amer. Assoc. Cancer Res., 45 925
2) Ciuffreda et al. (2009), Growth-inhibitor and antiangiogenic activity of the MEK inhibitor PD0325901 in malignant melanoma with or without BRAF mutations; Neoplasia, 11 720
3) Ai et al. (2016), Maintenance of Self-Renewal and Pluripotency in J1 Mouse Embryonic Stem Cells through Regulating Transcription Factor and MicroRNA Expression Induced by PD0325901; Stem Cells Int., 2016 1792573
4) Li et al. (2016), MEK inhibitor PD0325901 and vitamin C synergistically induce hypomethylation of mouse embryonic stem cells; Oncotarget, 7 39730
5) Li et al. (2009), Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors; Cell Stem Cell, 4 16
