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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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| Additional Infomation |
Aurora A Kinase/Tyrosine Kinase Inhibitor ENMD-2076 is an orally bioavailable synthetic small molecule with potential antiangiogenic and antineoplastic activities. Aurora A kinase/tyrosine kinase inhibitor ENMD-2076 selectively binds to and inhibits non-specified tyrosine kinases and Aurora kinases (AKs). The inhibition of AKs may result in the inhibition of cell division and proliferation and may induce apoptosis in tumor cells that overexpress AKs; antiangiogenic activity is related to the inhibition of angiogenic tyrosine kinases. AKs are serine-threonine kinases that play an essential role in mitotic checkpoint control during mitosis and are important regulators of cell division and proliferation.
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| Molecular Formula |
C21H25N7
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|---|---|
| Molecular Weight |
375.470103025436
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| Exact Mass |
375.217
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| CAS # |
934353-76-1
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| Related CAS # |
ENMD-2076 Tartrate;1453868-32-0
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| PubChem CID |
16041424
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| Appearance |
White to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
535.0±50.0 °C at 760 mmHg
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| Flash Point |
277.4±30.1 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.704
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| LogP |
1.31
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
499
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC(=NN1)NC2=CC(=NC(=N2)/C=C/C3=CC=CC=C3)N4CCN(CC4)C
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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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| HS Tariff Code |
2934.99.9001
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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) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.66 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (6.66 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.66 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 0.5% CMC+0.25% Tween 80:30mg/mL |
| 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00806065 | Completed | Drug: ENMD-2076 | Multiple Myeloma | CASI Pharmaceuticals, Inc. | December 2008 | Phase 1 |
| NCT00904787 | Completed | Drug: ENMD-2076 | Relapsed or Refractory Hematological Malignancies |
CASI Pharmaceuticals, Inc. | April 2009 | Phase 1 |
| NCT01104675 | Completed | Drug: ENMD-2076 | Ovarian Cancer Fallopian Cancer |
CASI Pharmaceuticals, Inc. | April 2010 | Phase 2 |
| NCT00658671 | Completed | Drug: ENMD-2076 | Advanced Cancer | CASI Pharmaceuticals, Inc. | April 2008 | Phase 1 |
Antiangiogenic action of ENMD-2076. Mol Cancer Ther. 2011 Jan;10(1):126-37. |
ENMD-2076 inhibits Flt3, VEGFR2/KDR, FGFR-1/2, and Aurora A in vivo. Mol Cancer Ther. 2011 Jan;10(1):126-37. |
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. |
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