| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| 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)
Aurora A kinase, FLT3, VEGFR2/KDR, VEGFR3/Flt4, FGFR1, FGFR2, Src, PDGFRalpha. ENMD-2076 is a multi-targeted kinase inhibitor with an IC50 of 1.86 nM for Aurora A, demonstrating selectivity over Aurora B (IC50 = 350 nM). |
|---|---|
| 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].
ENMD-2076 Tartrate inhibits Aurora A with an IC50 of 1.86 nM, FLT3 with an IC50 of 14 nM, VEGFR2/KDR with an IC50 of 58.2 nM, VEGFR3/Flt4 with an IC50 of 15.9 nM, FGFR1 with an IC50 of 92.7 nM, and FGFR2 with an IC50 of 70.8 nM. It also inhibits Src and PDGFRalpha. In HUVEC cells, it inhibits growth with an IC50 of 0.15 mM. |
| 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].
ENMD-2076 has demonstrated in vivo anti-tumor activity in xenograft models of AML, hepatocellular carcinoma, and multiple myeloma. It is orally active, and Phase 2 clinical trials have been conducted in AML patients. It has also shown activity in a Phase 2 trial for liver cancer. The tartrate salt enhances stability for oral administration. |
| Enzyme Assay |
Cell-free kinase assays are performed using recombinant Aurora A, FLT3, VEGFR2, and other kinases. The compound is incubated with the enzyme, a peptide substrate, and ATP for 30-60 minutes. Kinase activity is measured using a luminescence-based ADP detection kit. IC50 values are determined from dose-response curves.
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| Cell Assay |
For cellular assays, human leukemia cell lines (e.g., MV4-11) are seeded in 96-well plates and treated with ENMD-2076 for 72 hours. Cell viability is assessed by MTT assay. Apoptosis is measured by Annexin V/PI staining. HUVEC cells are used for anti-angiogenic assays, measuring tube formation. IC50 values range from 0.025 to 0.53 mM across 10 leukemia lines.
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| Animal Protocol |
For in vivo studies, ENMD-2076 is administered orally to mice bearing tumor xenografts. Dosing schedules vary by model but typically once daily for 2-4 weeks. Tumor volumes are measured with calipers. Plasma samples are collected for PK analysis. At study termination, tumors are excised for analysis of Aurora A, FLT3, and VEGFR2 target engagement.
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| ADME/Pharmacokinetics |
ENMD-2076 is orally bioavailable with favorable pharmacokinetic properties. The tartrate salt form enhances oral absorption and stability. In preclinical species, it achieves adequate systemic exposure for once-daily dosing. The compound has a moderate half-life and is metabolized in the liver, supporting progression into clinical studies.
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| Toxicity/Toxicokinetics |
In Phase 1 and 2 clinical trials, ENMD-2076 has shown a manageable safety profile. The most common adverse events include fatigue, hypertension, and gastrointestinal disturbances. No specific preclinical toxicity data are detailed, but as a multi-targeted kinase inhibitor, its safety profile is consistent with class-related effects.
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| References |
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| Additional Infomation |
See also: Enmd-2076 (Notes moved to).
Other information: ENMD-2076 Tartrate (CAS 1453868-32-0) is the tartrate salt of ENMD-2076. It has been evaluated in Phase 2 clinical trials for acute myeloid leukemia (NCT01553188, NCT02389387) and liver cancer. It is not yet FDA-approved. The compound is for research use only, and its tartrate salt form offers improved formulation properties. |
| Molecular Formula |
C25H31N7O6
|
|---|---|
| Molecular Weight |
525.56
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| Exact Mass |
525.233
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| CAS # |
1453868-32-0
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| Related CAS # |
ENMD-2076;934353-76-1
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| PubChem CID |
24776050
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| Appearance |
Light brown to khaki solid powder
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
38
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| Complexity |
633
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| 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
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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 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)
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| Solubility (In Vitro) |
DMSO: 25 mg/mL (47.57 mM)
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|---|---|
| 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 |
*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.
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