PD184161 is an orally-active MEK inhibitor. PD184161 inhibited MEK activity (IC50 = 10-100 nM) in a time- and concentration-dependent manner more effectively than PD098059 or U0126. PD184161 inhibited cell proliferation and induced apoptosis at concentrations of > or = 1.0 microM in a time- and concentration-dependent manner. PD184161 has antitumor effects in HCC in vitro and in vivo that appear to correlate with suppression of MEK activity. PD184161 is unable to suppress MEK activity in HCC xenografts in the long term.

MedKoo Cat#: 406196 Name: PD184161 CAS#: 212631-67-9 Chemical Formula: C17H13BrClF2IN2O2 Exact Mass: 555.88617 Molecular Weight: 557.55 Elemental Analysis: C, 36.62; H, 2.35; Br, 14.33; Cl, 6.36; F, 6.81; I, 22.76; N, 5.02; O, 5.74

Synonym: PD184161; PD 184161; PD184161; PF1529483 PF3011370 UK287074.

IUPAC/Chemical Name: 2-(2-chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluoro-5-bromobenzamide

InChi Key: VJNZMSLGVUSPCF-UHFFFAOYSA-N

InChi Code: InChI=1S/C17H13BrClF2IN2O2/c18-11-6-10(17(25)24-26-7-8-1-2-8)16(15(21)14(11)20)23-13-4-3-9(22)5-12(13)19/h4-6,8,23H,1-2,7H2,(H,24,25)

SMILES Code: O=C(NOCC1CC1)C2=CC(Br)=C(F)C(F)=C2NC3=CC=C(I)C=C3Cl

Technical Data

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code: 293490

Additional Information

        

References

1: Matsushita H, Matsuzaki M, Han XJ, Nishiki TI, Ohmori I, Michiue H, Matsui H, Tomizawa K. Antidepressant-like effect of sildenafil through oxytocin-dependent cyclic AMP response element-binding protein phosphorylation. Neuroscience. 2012 Jan 3;200:13-8. doi: 10.1016/j.neuroscience.2011.11.001. Epub 2011 Nov 9. PubMed PMID: 22088430.

2: Mazharian A, Watson SP, Séverin S. Critical role for ERK1/2 in bone marrow and fetal liver-derived primary megakaryocyte differentiation, motility, and proplatelet formation. Exp Hematol. 2009 Oct;37(10):1238-1249.e5. doi: 10.1016/j.exphem.2009.07.006. Epub 2009 Jul 18. PubMed PMID: 19619605; PubMed Central PMCID: PMC2755112.

3: Yip-Schneider MT, Klein PJ, Wentz SC, Zeni A, Menze A, Schmidt CM. Resistance to mitogen-activated protein kinase kinase (MEK) inhibitors correlates with up-regulation of the MEK/extracellular signal-regulated kinase pathway in hepatocellular carcinoma cells. J Pharmacol Exp Ther. 2009 Jun;329(3):1063-70. doi: 10.1124/jpet.108.147306. Epub 2009 Mar 3. PubMed PMID: 19258520.

4: Choi J, Yip-Schneider M, Albertin F, Wiesenauer C, Wang Y, Schmidt CM. The effect of doxorubicin on MEK-ERK signaling predicts its efficacy in HCC. J Surg Res. 2008 Dec;150(2):219-26. doi: 10.1016/j.jss.2008.01.029. Epub 2008 Mar 3. PubMed PMID: 18468633.

5: Duman CH, Schlesinger L, Russell DS, Duman RS. Voluntary exercise produces antidepressant and anxiolytic behavioral effects in mice. Brain Res. 2008 Mar 14;1199:148-58. doi: 10.1016/j.brainres.2007.12.047. Epub 2008 Jan 3. Erratum in: Brain Res. 2008 Jul 7;1218:313. PubMed PMID: 18267317; PubMed Central PMCID: PMC2330082.

6: Duman CH, Schlesinger L, Kodama M, Russell DS, Duman RS. A role for MAP kinase signaling in behavioral models of depression and antidepressant treatment. Biol Psychiatry. 2007 Mar 1;61(5):661-70. Epub 2006 Aug 30. PubMed PMID: 16945347.

7: Klein PJ, Schmidt CM, Wiesenauer CA, Choi JN, Gage EA, Yip-Schneider MT, Wiebke EA, Wang Y, Omer C, Sebolt-Leopold JS. The effects of a novel MEK inhibitor PD184161 on MEK-ERK signaling and growth in human liver cancer. Neoplasia. 2006 Jan;8(1):1-8. PubMed PMID: 16533420; PubMed Central PMCID: PMC1601146.

8: Thottassery JV, Sun Y, Westbrook L, Rentz SS, Manuvakhova M, Qu Z, Samuel S, Upshaw R, Cunningham A, Kern FG. Prolonged extracellular signal-regulated kinase 1/2 activation during fibroblast growth factor 1- or heregulin beta1-induced antiestrogen-resistant growth of breast cancer cells is resistant to mitogen-activated protein/extracellular regulated kinase kinase inhibitors. Cancer Res. 2004 Jul 1;64(13):4637-47. PubMed PMID: 15231676.

9: Yung HW, Wyttenbach A, Tolkovsky AM. Aggravation of necrotic death of glucose-deprived cells by the MEK1 inhibitors U0126 and PD184161 through depletion of ATP. Biochem Pharmacol. 2004 Jul 15;68(2):351-60. PubMed PMID: 15194007.

10: Marshall SJ, Senis YA, Auger JM, Feil R, Hofmann F, Salmon G, Peterson JT, Burslem F, Watson SP. GPIb-dependent platelet activation is dependent on Src kinases but not MAP kinase or cGMP-dependent kinase. Blood. 2004 Apr 1;103(7):2601-9. Epub 2003 Dec 18. PubMed PMID: 14684423.

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