Physicochemical Properties
| Molecular Formula | C25H31N7O6 |
| Molecular Weight | 525.56 |
| Exact Mass | 525.233 |
| CAS # | 1453868-32-0 |
| Related CAS # | ENMD-2076;934353-76-1 |
| PubChem CID | 24776050 |
| Appearance | Light brown to khaki solid powder |
| Hydrogen Bond Donor Count | 6 |
| Hydrogen Bond Acceptor Count | 12 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 38 |
| Complexity | 633 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | CC1=CC(=NN1)NC2=CC(=NC(=N2)/C=C/C3=CC=CC=C3)N4CCN(CC4)C.[C@@H]([C@H](C(=O)O)O)(C(=O)O)O |
| InChi Key | KGWWHPZQLVVAPT-STTJLUEPSA-N |
| InChi Code | InChI=1S/C21H25N7.C4H6O6/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;5-1(3(7)8)2(6)4(9)10/h3-9,14-15H,10-13H2,1-2H3,(H2,22,23,24,25,26);1-2,5-6H,(H,7,8)(H,9,10)/b9-8+;/t;1-,2-/m.1/s1 |
| Chemical Name | (2R,3R)-2,3-dihydroxybutanedioic acid;6-(4-methylpiperazin-1-yl)-N-(5-methyl-1H-pyrazol-3-yl)-2-[(E)-2-phenylethenyl]pyrimidin-4-amine |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Aurora A 1.86 nM (IC50) KDR 58.2 nM (IC50) Flt-4 15.9 nM (IC50) FGFR1 92.7 nM (IC50) FGFR2 70.8 nM (IC50) PDGFRα 56.4 nM (IC50) Flt3 14 nM (IC50) |
| ln Vitro | With an IC50 of 350 nM, ENMD-2076 exhibits selectivity toward Aurora A over Aurora B. HUVEC growth is inhibited by ENMD-2076, with an IC50 value of 0.15 mM. The IC50 values against ten human leukemia cell lines span from 0.025 to 0.53 mM. The most sensitive cells in this panel by a factor larger than four are MV4:11 cells. The ENMD-2076 treatment of the lymphoma-derived U937 cell line results in a dose-dependent increase in G2-M-phase arrest and apoptosis induction. With an IC50 value of 28 nM, ENMD-2076 suppresses Flt3 autophosphorylation induced by cellular Flt3 ligand (FL) in THP-1 cells, which express FL-responsive wild-type Flt-3 (18). With an IC50 value of 40 nM, ENMD-2076 prevents Kit autophosphorylation in MO7e cells caused by stem cell factor (SCF). With an IC50 value of 7 nM, ENMD-2076 inhibits VEGFR2/KDR autophosphorylation[1]. |
| ln Vivo | Tumor growth or regression is statistically significantly and dose-dependently inhibited by ENMD-2076 treatment. Additionally, there is no association between the rate of tumor growth and the effectiveness of the antitumor treatment, which is not surprising for a mitotic kinase inhibitor given that ENMD-2076 inhibits both slow-growing (such as HT29 colon carcinoma) and fast-growing (like A375 melanoma) tumors. With the exception of the A375 model, ENMD-2076 is well tolerated at daily doses up to 302 mg/kg (equivalent to 200 mg/kg of the free base), and no weight loss or morbidity symptoms have been observed in any study at this dose[1]. |
| References |
[1]. 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]. 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. |
| Additional Infomation | See also: Enmd-2076 (annotation moved to). |
Solubility Data
| Solubility (In Vitro) | DMSO: 25 mg/mL (47.57 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.43 mg/mL (2.72 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 14.3 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: ≥ 1.43 mg/mL (2.72 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 14.3 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9027 mL | 9.5137 mL | 19.0273 mL | |
| 5 mM | 0.3805 mL | 1.9027 mL | 3.8055 mL | |
| 10 mM | 0.1903 mL | 0.9514 mL | 1.9027 mL |