PD-0325901
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 202172

CAS#: 391210-10-9

Description: 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. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).


Price and Availability

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Price

10mg
USD 120
100mg
USD 450
1g
USD 2650
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Price

25mg
USD 150
200mg
USD 850
2g
USD 3950
Size
Price

50mg
USD 250
500mg
USD 1650
5g
Ask price

PD-0325901, 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. Delivery time: overnight (USA/Canada); 3-5 days (worldwide). Shipping fee: from $30.00 (USA); from $45.00 (Canada); from $70.00 (international).


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 202172
Name: PD-0325901
CAS#: 391210-10-9
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


Synonym: PD0325901; PD 0325901; PD-325901.

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


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, not in water

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

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 non–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); OF1–8 ].
  
 
 


References

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, Foà 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.