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ENMD-2076

Cat. No. M1706
ENMD-2076 Structure
Size Price Availability Quantity
10mg USD 265 In stock
50mg USD 795 In stock
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Quality Control
Biological Activity

ENMD-2076 is an orally-active, Aurora A/angiogenic kinase inhibitor with a unique kinase selectivity profile and multiple mechanisms of action. ENMD-2076 has been shown to inhibit a distinct profile of angiogenic tyrosine kinase targets in addition to the Aurora A kinase. ENMD-2076 also targets the VEGFR, Flt-3 and FGFR3 kinases which have been shown to play important roles in the pathology of several cancers. ENMD-2076 has shown promising activity in Phase 1 clinical trials in solid tumor cancers, leukemia, and multiple myeloma. ENMD-2076 is currently in a Phase 2 trial for ovarian cancer, and preclinical and clinical activities are ongoing in assessing the compound's applicability for other forms of cancer.

Protocol
Cell Experiment
Cell lines solid tumor cell lines and HUVECs, human leukemia cell lines
Preparation method Cell and proliferative assays
Cell lines were routinely tested for mycoplasma and used at low passage numbers (<10). The antiproliferative effect of ENMD-2076 on adherent tumor cell lines was measured by plating 500 cells per well in a 96-well plate and incubating with 9 doses of compound, spanning 0.3 nmol/L to 125 μmol/L, for 96 hours. Cellular proliferation was measured using the sulforhodamine B (SRB; Sigma Aldrich) assay (10). The leukemia-derived, nonadherent cell lines were assayed by plating 5,000 cells per well in a 96-well plate. The cells were incubated with 9 doses of compound, spanning 0.3 nmol/L to 125 μmol/L, for 48 hours and then survival was assayed using the Alamar Blue reagent (Invitrogen) according to the manufacturer’s instructions. To measure the effect of ENMD-2076 on VEGF- and fibroblast growth factor (FGF)-induced proliferation of human umbilical vein endothelial cell (HUVEC), cells were serum starved for 6 hours, then treated with ENMD-2076 free base, and stimulated with 5 ng/mL bFGF or 25 ng/mL VEGF (R and D Systems) for 72 hours. Cell proliferation was measured using WST-1 (Roche Applied Science) according to the manufacturer’s instructions.
Concentrations 0.3 nM~125 μM
Incubation time 48 or 96 h
Animal Experiment
Animal models MDA-MB-231 tumor xenograft model of 5- to 6-week-old CB.17 SCID or NCr nude mice
Formulation ENMD-2076 in water or ENMD-2076 free base in CMC-Tween vehicle (0.075% carboxymethylcellulose, 0.085% Tween 80 in water)
Dosages 75 or 302 mg/kg daily
Administration orally
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 525.56
Formula C25H31N7O6
CAS Number 934353-76-1
Purity >99%
Solubility DMSO
Storage at -20°C
References

ENMD-2076, an oral inhibitor of angiogenic and proliferation kinases, has activity in recurrent, platinum resistant ovarian cancer.
Matulonis et al. Eur J Cancer. 2012 Aug 21. PMID: 22921155.

ENMD-2076 for hematological malignancies.
How et al. Expert Opin Investig Drugs. 2012 May;21(5):717-32. PMID: 22397360.

From cell biology to therapy: ENMD-2076 in the treatment of multiple myeloma.
Zhang et al. Expert Opin Investig Drugs. 2011 Jul;20(7):1015-28. PMID: 21615212.

ENMD-2076 is an orally active kinase inhibitor with antiangiogenic and antiproliferative mechanisms of action.
Fletcher et al. Mol Cancer Ther. 2011 Jan;10(1):126-37. PMID: 21177375.

Phase I safety, pharmacokinetic, and pharmacodynamic study of ENMD-2076, a novel angiogenic and Aurora kinase inhibitor, in patients with advanced solid tumors.
Diamond et al. Clin Cancer Res. 2011 Feb 15;17(4):849-60. PMID: 21131552.

Preclinical activity of a novel multiple tyrosine kinase and aurora kinase inhibitor, ENMD-2076, against multiple myeloma.
Wang et al. Br J Haematol. 2010 Aug;150(3):313-25. PMID: 20560971.

Assessment of the in vivo antitumor effects of ENMD-2076, a novel multitargeted kinase inhibitor, against primary and cell line-derived human colorectal cancer xenograft models.
Tentler et al. Clin Cancer Res. 2010 Jun 1;16(11):2989-98. PMID: 20406842.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: ENMD-2076 supplier, Aurora Kinase, inhibitors

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