WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 202172
Description: Mirdametinib, also known as PD-0325901, is a potent bioavailable and selective MEK inhibitor, which targets mitogen-activated protein kinase kinase (MAPK/ERK kinase or MEK) with potential antineoplastic activity. MEK inhibitor PD325901, a derivative of MEK inhibitor CI-1040, selectively binds to and inhibits MEK, which may result in the inhibition of the phosphorylation and activation of MAPK/ERK and the inhibition of tumor cell proliferation. The dual specific threonine/tyrosine kinase MEK is a key component of the RAS/RAF/MEK/ERK signaling pathway that is frequently activated in human tumors.
MedKoo Cat#: 202172
Chemical Formula: C16H14F3IN2O4
Exact Mass: 481.99503
Molecular Weight: 482.19304
Elemental Analysis: C, 39.85; H, 2.93; F, 11.82; I, 26.32; N, 5.81; O, 13.27
Mirdametinib, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.
Synonym: PD0325901; PD 0325901; PD-325901; mirdametinib
IUPAC/Chemical Name: (R)-N-(2,3-dihydroxypropoxy)-3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzamide
InChi Key: SUDAHWBOROXANE-SECBINFHSA-N
InChi Code: InChI=1S/C16H14F3IN2O4/c17-11-3-2-10(16(25)22-26-7-9(24)6-23)15(14(11)19)21-13-4-1-8(20)5-12(13)18/h1-5,9,21,23-24H,6-7H2,(H,22,25)/t9-/m1/s1
SMILES Code: O=C(NOC[C@H](O)CO)C1=CC=C(F)C(F)=C1NC2=CC=C(I)C=C2F
The following data is based on the product molecular weight 482.19304 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
1: Paulo JA, McAllister FE, Everley RA, Beausoleil SA, Banks AS, Gygi SP. Effects of MEK inhibitors GSK1120212 and PD0325901 in vivo using 10-plex quantitative proteomics and phosphoproteomics. Proteomics. 2014 Sep 5. doi: 10.1002/pmic.201400154. [Epub ahead of print] PubMed PMID: 25195567.
2: El-Hoss J, Cheng T, Carpenter EC, Sullivan K, Deo N, Mikulec K, Little DG, Schindeler A. A Combination of rhBMP-2 (Recombinant Human Bone Morphogenetic Protein-2) and MEK (MAP Kinase/ERK Kinase) Inhibitor PD0325901 Increases Bone Formation in a Murine Model of Neurofibromatosis Type I Pseudarthrosis. J Bone Joint Surg Am. 2014 Jul 16;96(14):e117. [Epub ahead of print] PubMed PMID: 25031379.
3: El-Hoss J, Kolind M, Jackson MT, Deo N, Mikulec K, McDonald MM, Little CB, Little DG, Schindeler A. Modulation of endochondral ossification by MEK inhibitors PD0325901 and AZD6244 (Selumetinib). Bone. 2014 Feb;59:151-61. doi: 10.1016/j.bone.2013.11.013. Epub 2013 Nov 20. PubMed PMID: 24269278.
4: Sheth PR, Liu Y, Hesson T, Zhao J, Vilenchik L, Liu YH, Mayhood TW, Le HV. Fully activated MEK1 exhibits compromised affinity for binding of allosteric inhibitors U0126 and PD0325901. Biochemistry. 2011 Sep 20;50(37):7964-76. doi: 10.1021/bi200542r. Epub 2011 Aug 26. PubMed PMID: 21793567.
5: Henderson YC, Chen Y, Frederick MJ, Lai SY, Clayman GL. MEK inhibitor PD0325901 significantly reduces the growth of papillary thyroid carcinoma cells in vitro and in vivo. Mol Cancer Ther. 2010 Jul;9(7):1968-76. doi: 10.1158/1535-7163.MCT-10-0062. Epub 2010 Jun 29. PubMed PMID: 20587665; PubMed Central PMCID: PMC2935263.
6: Hennig M, Yip-Schneider MT, Wentz S, Wu H, Hekmatyar SK, Klein P, Bansal N, Schmidt CM. Targeting mitogen-activated protein kinase kinase with the inhibitor PD0325901 decreases hepatocellular carcinoma growth in vitro and in mouse model systems. Hepatology. 2010 Apr;51(4):1218-25. doi: 10.1002/hep.23470. PubMed PMID: 20112426.
7: Huang W, Yang AH, Matsumoto D, Collette W, Marroquin L, Ko M, Aguirre S, Younis HS. PD0325901, a mitogen-activated protein kinase kinase inhibitor, produces ocular toxicity in a rabbit animal model of retinal vein occlusion. J Ocul Pharmacol Ther. 2009 Dec;25(6):519-30. doi: 10.1089/jop.2009.0060. PubMed PMID: 19929595.
8: Ciuffreda L, Del Bufalo D, Desideri M, Di Sanza C, Stoppacciaro A, Ricciardi MR, Chiaretti S, Tavolaro S, Benassi B, Bellacosa A, FoÃ R, Tafuri A, Cognetti F, Anichini A, Zupi G, Milella M. Growth-inhibitory and antiangiogenic activity of the MEK inhibitor PD0325901 in malignant melanoma with or without BRAF mutations. Neoplasia. 2009 Aug;11(8):720-31. PubMed PMID: 19649202; PubMed Central PMCID: PMC2713590.
9: Leyton J, Smith G, Lees M, Perumal M, Nguyen QD, Aigbirhio FI, Golovko O, He Q, Workman P, Aboagye EO. Noninvasive imaging of cell proliferation following mitogenic extracellular kinase inhibition by PD0325901. Mol Cancer Ther. 2008 Sep;7(9):3112-21. doi: 10.1158/1535-7163.MCT-08-0264. PubMed PMID: 18790789.
10: Liu D, Xing M. Potent inhibition of thyroid cancer cells by the MEK inhibitor PD0325901 and its potentiation by suppression of the PI3K and NF-kappaB pathways. Thyroid. 2008 Aug;18(8):853-64. doi: 10.1089/thy.2007.0357. PubMed PMID: 18651802; PubMed Central PMCID: PMC2857450.
11: Brown AP, Carlson TC, Loi CM, Graziano MJ. Pharmacodynamic and toxicokinetic evaluation of the novel MEK inhibitor, PD0325901, in the rat following oral and intravenous administration. Cancer Chemother Pharmacol. 2007 Apr;59(5):671-9. Epub 2006 Aug 31. PubMed PMID: 16944149.
Phase II clinical trials was published in 2010. The study propose was to evaluate the efficacy of mitogen-activated protein kinase/extracellular signal-related kinase kinase inhibitor PD-0325901 in advanced nonÂ–small cell lung cancer patients who had experienced treatment failure after, or were refractory to, standard systemic therapy. All patients had received prior systemic therapy (median of two regimens, including epidermal growth factor receptor inhibitors in 26%). Of 13 patients treated on schedule A, three discontinued due to adverse events (blurred vision, fatigue, and hallucinations, respectively). Twenty-one patients received schedule B. Main toxicities included diarrhea, fatigue, rash, vomiting, nausea, and reversible visual disturbances. Hematologic toxicity consisted mainly of mild-to-moderate anemia, without neutropenia. Chemistry abnormalities were rare. Mean (coefficient of variation) PD-0325901 trough plasma concentrations were 100 ng/mL (52%) and 173 ng/mL (73%) for schedules A and B, respectively, above the minimum target concentration established in preclinical studies (16.5 ng/mL). There were no objective responses. Seven patients had stable disease. Median (95% confidence interval) progression-free survival was 1.8 months (1.5-1.9) and overall survival was 7.8 months (4.5-13.9). Conclusions: PD-0325901 did not meet its primary efficacy end point. Future studies should focus on PD-0325901 schedule, rational combination strategies, and enrichment of patient selection based on mode of action. [source: Clin Cancer Res; 16(8); OF1Â–8 ].