PD 184352, Free Base **

产品名称：PD 184352, Free Base
产品货号：LC  P-8499
产品规格：10 MG
PD184352 is an inhibitor of mitogen activated protein kinase kinase (MEK or MAPKK).
Antitumor activity of PD184352 is evident in preclinical models, including pancreas, colon, and breast cancers, which are associated with its inhibition of pERK.  Allen, L.F., et al.  "CI-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK)."  Semin. Oncol. 30:  105-116 (2003).
PD184352 profoundly inhibited the growth of, and induced apoptosis in, ovarian tumor cells with mutations in either KRAS or BRAF.  However, ovarian cancer cells containing wild-type sequences were not sensitive to PD184352.  Pohl, G., et al.  "Inactivation of the mitogen-activated protein kinase pathway as a potential target-based therapy in ovarian serous tumors with KRAS or BRAF mutations."  Cancer Res. 65:  1994-2000 (2005).
PD184352 inhibited C-Raf with an IC50 of 12 nM and inhibited more than 90% of ERK phosphorylation at a concentration of 10 nM.  In vivo, PD184352 decreased adenoma formation and significantly restored lung structure.  Kramer, B.W., et al.  "Use of mitogenic cascade blockers for treatment of C-Raf induced lung adenoma in vivo:  CI-1040 strongly reduces growth and improves lung structure."  BMC Cancer 4:  24 (2004).
PD184352 inhibited the MAPK pathway and induced apoptosis through a pathway involved in dephosphorylation, aggregation of Fas-associated death domain protein, and death receptor-independent caspase-8 activation.  Meng, X.W., et al.  "Central Role of Fas-associated Death Domain Protein in Apoptosis Induction by the Mitogen-activated Protein Kinase Kinase Inhibitor CI-1040 (PD184352) in Acute Lymphocytic Leukemia Cells in Vitro."  J. Biol. Chem. 278:  47326-47339 (2003).
However, PD184352 suffered from poor pharmacokinetics because of its low solubility and rapid clearance.  Barrett, S.D., et al.  "The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901."  Bioorg. Med. Chem. Lett. 18:  6501-6504 (2008).
Storage:  Store at or below -20 ºC.  Solubility:  Soluble in DMSO at 50 mg/mL; soluble in ethanol at 8.3 mg/mL with slight warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 5-10 µM buffers, serum, or other additives may increase or decrease the aqueous solubility.  Disposal:  A

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