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1mg |
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10mg |
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25mg |
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100mg |
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Purity: ≥98%
ENMD-2076 (ENMD2076) is a novel,potent and orally bioactive inhibitor of multikinase including Aurora A and Flt3 with potential antitumor activity. It inhibits Aurora A and Flt3 with IC50s of 14 nM and 1.86 nM, respectively, and exhibits 25-fold selectivity for Aurora A over Aurora B. It shows potent in vitro antiproliferative activity and high in vivo antitumor efficacy.
ln Vitro |
ENMD-2076 is specific for Aurora A over Aurora B (IC50=350 nM). ENMD-2076 inhibits HUVEC proliferation at an IC50 of 0.15 mM. The IC50 values for 10 human leukemia cell lines range from 0.025 to 0.53 mM. In this panel, MV4:11 cells are the most responsive by a factor of more than 4. The lymphoma-derived U937 cell line treated with ENMD-2076 demonstrates a dose-dependent increase in G2-M-phase arrest and apoptosis. ENMD-2076 suppresses cellular Flt3 ligand (FL)-induced Flt3 autophosphorylation in THP-1 cells, which have been demonstrated to express FL-responsive wild-type Flt-3 (18), with an IC50 of 28 nM. ENMD-2076 inhibits stem cell factor (SCF)-induced Kit autophosphorylation in MO7e cells with an IC50 of 40 nM. ENMD-2076 inhibits VEGFR2/KDR autophosphorylation with an IC50 of 7 nM [1].
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ln Vivo |
Treatment with ENMD-2076 leads to statistically significant tumor growth or regression inhibition that is dose dependent. Furthermore, as fast-growing tumors like A375 melanoma and slow-growing tumors like HT29 colon carcinoma are similarly inhibited by ENMD-2076, there is no correlation between tumor growth rate and antitumor efficacy, which is theoretically expected for a mitotic kinase inhibitor. With the exception of the A375 model, studies have not found any weight loss or indications of morbidity at daily doses of up to 302 mg/kg (equivalent to 200 mg/kg of the free base) for ENMD-2076.
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Animal Protocol |
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References |
[1]. Fletcher GC, et al. ENMD-2076 is an orally active kinase inhibitor with antiangiogenic and antiproliferative mechanisms of action. Mol Cancer Ther. 2011 Jan;10(1):126-37.
[2]. Wang X, et al. Preclinical activity of a novel multiple tyrosine kinase and aurora kinase inhibitor, ENMD-2076, against multiple myeloma. Br J Haematol. 2010 Aug;150(3):313-25 |
Molecular Formula |
C21H25N7
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Molecular Weight |
375.470103025436
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CAS # |
934353-76-1
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SMILES |
CN1CCN(C2=CC(NC3=NNC(C)=C3)=NC(/C=C/C4=CC=CC=C4)=N2)CC1
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InChi Key |
BLQYVHBZHAISJM-CMDGGOBGSA-N
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InChi Code |
InChI=1S/C21H25N7/c1-16-14-20(26-25-16)23-19-15-21(28-12-10-27(2)11-13-28)24-18(22-19)9-8-17-6-4-3-5-7-17/h3-9,14-15H,10-13H2,1-2H3,(H2,22,23,24,25,26)/b9-8+
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Chemical Name |
(E)-N-(5-methyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-styrylpyrimidin-4-amine.
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Synonyms |
ENMD 2076; ENMD-2076; ENMD2076.
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.6633 mL | 13.3166 mL | 26.6333 mL | |
5 mM | 0.5327 mL | 2.6633 mL | 5.3267 mL | |
10 mM | 0.2663 mL | 1.3317 mL | 2.6633 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Antiangiogenic action of ENMD-2076. Mol Cancer Ther. 2011 Jan;10(1):126-37. td> |
ENMD-2076 inhibits Flt3, VEGFR2/KDR, FGFR-1/2, and Aurora A in vivo. Mol Cancer Ther. 2011 Jan;10(1):126-37. td> |
ENMD-2076 inhibits blood vessel formation and impacts the growth of established MDA-MB-231 tumors. Mol Cancer Ther. 2011 Jan;10(1):126-37. td> |