U0126

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

MedKoo CAT#: 404210

CAS#: 109511-58-2

Description: U0126 is a potent and selective non-competitive inhibitor of MAP kinase. Inhibits MEK-1 and MEK-2 (IC50 values of 0.07 and 0.06 μM respectively).


Price and Availability

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U0126 is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 404210
Name: U0126
CAS#: 109511-58-2
Chemical Formula: C18H16N6S2
Exact Mass: 380.08779
Molecular Weight: 380.48984
Elemental Analysis: C, 56.82; H, 4.24; N, 22.09; S, 16.85


Related CAS #: 109511-58-2 (free)   1173097-76-1 (EtOH)  

Synonym: U0126, U 0126, U-0126

IUPAC/Chemical Name: (2Z,3Z)-2,3-bis(amino((2-aminophenyl)thio)methylene)succinonitrile

InChi Key: DVEXZJFMOKTQEZ-JYFOCSDGSA-N

InChi Code: InChI=1S/C18H16N6S2/c19-9-11(17(23)25-15-7-3-1-5-13(15)21)12(10-20)18(24)26-16-8-4-2-6-14(16)22/h1-8H,21-24H2/b17-11+,18-12+

SMILES Code: N#CC(/C(C#N)=C(N)/SC1=CC=CC=C1N)=C(N)\SC2=CC=CC=C2N


Technical Data

Appearance:
White to off-white 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:
>5 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

U0126, is a highly selective inhibitor of both MEK1 and MEK2, a type of MAPK/ERK kinase. U0126 was found to functionally antagonize AP-1 transcriptional activity via noncompetitive inhibition of the dual specificity kinase MEK with IC50 of 72 nM for MEK1 and 58 nM for MEK2. U0126 inhibited anchorage-independent growth of Ki-ras-transformed rat fibroblasts by simultaneously blocking both extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR)-p70(S6K) pathways. The effects of U0126 on the growth of eight human breast cancer cell lines shown that U0126 selectively repressed anchorage-independent growth of MDA-MB231 and HBC4 cells, two lines with constitutively activated ERK. Loss of contact with substratum triggers apoptosis in many normal cell types, a phenomenon termed anoikis. U0126 sensitized MDA-MB231 and HBC4 to anoikis, i.e., upon treatment with U0126, cells deprived of anchorage entered apoptosis. U0126 is also a weak inhibitor of PKC, Raf, ERK, JNK, MEKK, MKK-3, MKK-4/SEK, MKK-6, Cdk2 and Cdk4  (source: http://en.wikipedia.org/wiki/U0126)


References

1: Ma DM, Ji YJ, Yang F, Liu W, Wan Z, Li RY. Effects of U0126 on growth and activation of mitogen-activated protein kinases in Aspergillus fumigatus. Chin Med J (Engl). 2013 Jan;126(2):220-5. PubMed PMID: 23324267.

2: Bae SH, Hwang JW, Shin SJ, Park GH, Yoon KD, Bae SK. Quantitation and pharmacokinetics of 1,4-diamino-2,3-dicyano-1,4-bis (2-aminophenylthio) butadiene (U0126) in rat plasma by liquid chromatography-tandem mass spectrometry. J Sep Sci. 2012 Dec 10. doi: 10.1002/jssc.201200779. [Epub ahead of print] PubMed PMID: 23225735.

3: Li J, Fan Y, Zhang YN, Sun DJ, Fu SB, Ma L, Jiang LH, Cui C, Ding HF, Yang J. The Raf-1 inhibitor GW5074 and the ERK1/2 pathway inhibitor U0126 ameliorate PC12 cells apoptosis induced by 6-hydroxydopamine. Pharmazie. 2012 Aug;67(8):718-24. PubMed PMID: 22957439.

4: Lodi A, Woods SM, Ronen SM. Treatment with the MEK inhibitor U0126 induces decreased hyperpolarized pyruvate to lactate conversion in breast, but not prostate, cancer cells. NMR Biomed. 2012 Sep 3. doi: 10.1002/nbm.2848. [Epub ahead of print] PubMed PMID: 22945392; PubMed Central PMCID: PMC3529990.

5: Flores LG 2nd, Yeh HH, Soghomonyan S, Young D, Bankson J, Hu Q, Alauddin M, Huff V, Gelovani JG. Monitoring Therapy with MEK Inhibitor U0126 in a Novel Wilms Tumor Model in Wt1 Knockout Igf2 Transgenic Mice Using (18)F-FDG PET with Dual-Contrast Enhanced CT and MRI: Early Metabolic Response Without Inhibition of Tumor Growth. Mol Imaging Biol. 2012 Aug 9. [Epub ahead of print] PubMed PMID: 22875335.

6: Zhang WZ, Wang ZG, Chen YQ, Ma L, Li T, Bao HG, Li PH. [Effects of valsartan and U0126 on atrial fibrosis and connexin40 remodeling in rats]. Zhonghua Xin Xue Guan Bing Za Zhi. 2011 Dec;39(12):1129-34. Chinese. PubMed PMID: 22336507.

7: Freeman MR, Kim J, Lisanti MP, Di Vizio D. A metabolic perturbation by U0126 identifies a role for glutamine in resveratrol-induced cell death. Cancer Biol Ther. 2011 Dec 1;12(11):966-77. doi: 10.4161/cbt.12.11.18136. Epub 2011 Dec 1. PubMed PMID: 22108021; PubMed Central PMCID: PMC3280915.

8: Zou ZQ, Zhang LN, Wang F, Bellenger J, Shen YZ, Zhang XH. The novel dual PI3K/mTOR inhibitor GDC-0941 synergizes with the MEK inhibitor U0126 in non-small cell lung cancer cells. Mol Med Report. 2012 Feb;5(2):503-8. doi: 10.3892/mmr.2011.682. Epub 2011 Nov 16. PubMed PMID: 22101421.

9: Droebner K, Pleschka S, Ludwig S, Planz O. Antiviral activity of the MEK-inhibitor U0126 against pandemic H1N1v and highly pathogenic avian influenza virus in vitro and in vivo. Antiviral Res. 2011 Nov;92(2):195-203. doi: 10.1016/j.antiviral.2011.08.002. Epub 2011 Aug 11. PubMed PMID: 21854809.

10: 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.

11: Marampon F, Gravina GL, Di Rocco A, Bonfili P, Di Staso M, Fardella C, Polidoro L, Ciccarelli C, Festuccia C, Popov VM, Pestell RG, Tombolini V, Zani BM. MEK/ERK inhibitor U0126 increases the radiosensitivity of rhabdomyosarcoma cells in vitro and in vivo by downregulating growth and DNA repair signals. Mol Cancer Ther. 2011 Jan;10(1):159-68. doi: 10.1158/1535-7163.MCT-10-0631. PubMed PMID: 21220498; PubMed Central PMCID: PMC3064485.

12: Ito M, Zhao N, Zeng Z, Chang CC, Zu Y. Synergistic growth inhibition of anaplastic large cell lymphoma cells by combining cellular ALK gene silencing and a low dose of the kinase inhibitor U0126. Cancer Gene Ther. 2010 Sep;17(9):633-44. doi: 10.1038/cgt.2010.20. Epub 2010 May 7. PubMed PMID: 20448669; PubMed Central PMCID: PMC2919633.

13: Miwa M, Uchida S, Horiba F, Takeshima H, Nabeshima T, Hiramatsu M. Nociceptin and its metabolite attenuate U0126-induced memory impairment through a nociceptin opioid peptide (NOP) receptor-independent mechanism. Neurobiol Learn Mem. 2010 Mar;93(3):396-405. doi: 10.1016/j.nlm.2009.12.006. Epub 2009 Dec 21. PubMed PMID: 20026233.

14: Zhao LY, Huang C, Li ZF, Liu L, Ni L, Song TS. STAT1/2 is involved in the inhibition of cell growth induced by U0126 in HeLa cells. Cell Mol Biol (Noisy-le-grand). 2009 Nov 15;55 Suppl:OL1168-74. PubMed PMID: 20003811.

15: Chen CL, Li TP, Zhu LH. [Effect of MAPK signal transduction pathway inhibitor U0126 on aquaporin 4 expression in alveolar type II cells in rats with oleic acid-induced acute lung injury]. Nan Fang Yi Ke Da Xue Xue Bao. 2009 Aug;29(8):1525-8. Chinese. PubMed PMID: 19726282.

16: Quan H, Liu H, Li C, Lou L. 1,4-Diamino-2,3-dicyano-1,4-bis(methylthio)butadiene (U0126) enhances the cytotoxicity of combretastatin A4 independently of mitogen-activated protein kinase kinase. J Pharmacol Exp Ther. 2009 Jul;330(1):326-33. doi: 10.1124/jpet.109.153320. Epub 2009 Apr 18. PubMed PMID: 19377096.

17: Marampon F, Bossi G, Ciccarelli C, Di Rocco A, Sacchi A, Pestell RG, Zani BM. MEK/ERK inhibitor U0126 affects in vitro and in vivo growth of embryonal rhabdomyosarcoma. Mol Cancer Ther. 2009 Mar;8(3):543-51. doi: 10.1158/1535-7163.MCT-08-0570. Epub 2009 Mar 3. PubMed PMID: 19258428.

18: Yao XL, Chen ZD, Tan FQ, Lu Y, Hu Q. [Protective effect of MEK inhibitor (U0126) on donor testes from ischemia-reperfusion injury after orthotopic testicular transplantation in rats]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2009 Jan;38(1):81-8. Chinese. PubMed PMID: 19253433.

19: Farrokhnia N, Ericsson A, Terént A, Lennmyr F. MEK-inhibitor U0126 in hyperglycaemic focal ischaemic brain injury in the rat. Eur J Clin Invest. 2008 Sep;38(9):679-85. doi: 10.1111/j.1365-2362.2008.01990.x. PubMed PMID: 18837745.

20: Bachleda P, Dvorák Z. Pharmacological inhibitors of JNK and ERK kinases SP600125 and U0126 are not appropriate tools for studies of drug metabolism because they activate aryl hydrocarbon receptor. Gen Physiol Biophys. 2008 Jun;27(2):143-5. PubMed PMID: 18645229.