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.
| 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 |
| Molecular Weight | 525.56 |
| Formula | C25H31N7O6 |
| CAS Number | 934353-76-1 |
| Solubility (25°C) | DMSO |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| 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 Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 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 Compound A of 10 mg/kg.
[2] How et al. Expert Opin Investig Drugs. ENMD-2076 for hematological malignancies.
| Related Aurora Kinase Products |
|---|
| Aurora Kinases-IN-4
Aurora Kinases-IN-4 is a covalent and ATP competitive aurora kinase A inhibitor (IC50: 1.7 nM). |
| Derrone
Derrone, a prenylated isoflavones, is an Aurora kinase inhibitor, with IC50 values of 6 and 22.3 μM against Aurora B and Aurora A, respectively. Derrone shows anti-tumor activity. |
| CD532 hydrochloride
CD532 hydrochloride is a potent Aurora A kinase inhibitor with an IC50 of 45 nM. CD532 hydrochloride has the dual effect of blocking Aurora A kinase activity and driving degradation of MYCN. CD532 hydrochloride also can directly interact with AURKA and induces a global conformational shift. CD532 hydrochloride can be used for the research of cancer. |
| Aurora kinase inhibitor-2
Aurora kinase inhibitor-2 is a selective and ATP-competitive Aurora kinase inhibitor with IC50s of 310 nM and 240 nM for Aurora A and Aurora B, respectively. |
| AAPK-25
AAPK-25 is a potent and selective Aurora/PLK dual inhibitor with anti-tumor activity, which can cause mitotic delay and arrest cells in a prometaphase, reflecting by the biomarker histone H3Ser10 phosphorylation and followed by a surge in apoptosis. AAPK-25 targets Aurora-A, -B, and -C with Kd values ranging from 23-289 nM, as well as PLK-1, -2, and -3 with Kd values ranging from 55-456 nM. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.
