PD0325901

PD0325901 is a potent non-ATP-competitive MEK inhibitor (IC₅₀ = 0.33 nM), exhibiting an apparent K_i of 1 nM against activated MEK1 and MEK2. PD0325901 selectively inhibits MEK, which may result in the inhibition of phosphorylation and activation of the MAPK/ERK pathways and tumor cell proliferation.

PD0325901 has been shown to promote OCT4-mediated reprogramming methods⁴ and increase reprogramming efficiency of fibroblasts to induced pluripotent stem cells (iPSC) when used along with the ALK5 inhibitor SB431542³. When used with CHIR99021 and A83-01, PD0325901 has been shown to generate “ground state” iPSC from somatic cells⁶.

Alternative names: PD325901; Mirdametinib
Applications: Pluripotent Stem Cell Culture; Reprogramming; Mouse ES Cell Culture; Cancer research

Features & Benefits

• Non-ATP-competitive MEK inhibitor
• Increases iPSC reprogramming efficiency with SB431542
• Promotes OCT4-mediated reprogramming to iPSC

Solubility Table

Keywords: PD0325901; Mirdametinib; PD325901; MEK; mitogen-activated protein kinase kinase; MAPK; Autophagy; Apoptosis; Reprogramming;

Documents

• Brochure: Small Molecules for Stem Cell Research
• FAQs: General Guide for Small Molecules

References and Publications

1. Tojo, M., et al. The ALK-5 inhibitor A-83-01 inhibits Smad signaling and epithelial-to-mesenchymal transition by transforming growth factorβ. Cancer Sci 96: 791-800 (2005).
2. Li, W., et al. Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors. Cell Stem Cell 4: 16-19 (2009).
3. Zhou et al. Conversion of mouse epiblast stem cells to an earlier pluripotency state by small molecules. J Bio Chem 285(39); 29676-80 (2010).
4. Zhu et al., Reprogramming of human primary somatic cells by OCT4 and chemical compounds. Cell Stem Cell 7(6): 651-5 (2010).
5. Zhang et al. Pharmacological reprogramming of fibroblasts into neural stem cells by signaling-directed transcriptional activation. Cell Stem Cell 18(5): 653-67 (2016).
6. Taniguchi Y, et al. Enhanced antitumor efficacy of folate-linked liposomal Adriamycin with TGF-β type I receptor inhibitor. Cancer Sci. 2010 Oct;101(10):2207-13.