ENMD-2076

SKU: orb1305600

Description

ENMD-2076 is a multi-targeted kinase inhibitor with potent activity against Aurora A, Flt3, VEGFR2/3, FGFR1/2, Src, and PDGFRα. It has demonstrated antitumor efficacy in preclinical models, supporting its investigation in oncology research for cancers dependent on these signaling pathways, including breast and ovarian malignancies.

Research Area

Cardiovascular Research, Cell Biology, Epigenetics & Chromatin, Signal Transduction

Key Properties

• CAS Number: 934353-76-1
• MW: 375.47
• Purity: 98.00% (May vary between batches)
• Formula: C₂₁H₂₅N₇
• SMILES: CN1CCN(CC1)c1cc(Nc2cc(C)[nH]n2)nc(\C=C\c2ccccc2)n1
• Target: Src,Aurora Kinase,FLT,c-RET,VEGFR,PDGFR,Apoptosis,FGFR
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (8.79 mM);DMSO:97 mg/mL (258.34 mM);H2O:1 mg/mL (2.66 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  KDR:58.2 nM|Aurora A:14 nM|FGFR1:92.7 nM|PDGFRα:56.4 nM|FLT3:1.86 nM|FGFR2:70.8 nM|VEGFR3/FLT4:15.9 nM|RET:10.4 nM|Src:20.2 nM
• In Vivo:
  ENMD-2076 targets the PI3K/AKT pathway, leading to the downregulation of apoptosis-inhibiting proteins. It inhibits aurora kinases A and B, causing cell cycle arrest at the G2/M phase. ENMD-2076 is effective against various angiogenesis-related kinases (IC50=1.86-120 nM), including VEGFR2/KDR, VEGFR3, FGFR1, FGFR2, and PDGFRα. In multiple human solid tumor and leukemia cell lines (IC50=0.025-0.7 μM), it induces cell cycle arrest at the G2/M phase and promotes apoptosis.
• In Vitro:
  In the MDA-MB-231 xenograft model, ENMD-2076 was observed to inhibit neovascularization while also inducing regression in already formed vessels. Within the HT29 xenograft model, ENMD-2076 consistently inhibited the activation of Flt3, as well as VEGFR2 / KDR and FGFR1 / 2. In the case of H929 human myeloma xenografts, oral administration of ENMD-2076 (50-200 mg/kg/day) resulted in a significant decrease in phospho-histone 3 (pH3) and Ki-67, alongside a notable increase in cleaved caspase-3, indicating effective antitumor activity through inhibition of cell proliferation and induction of apoptosis.
• Cell Research:
  The antiproliferative effect of ENMD-2076 on adherent tumor cell lines is measured by plating 500 cells per well in a 96-well plate and incubating with ENMD-2076 for 96 hours. Cellular proliferation is measured using the sulforhodamine B assay. The leukemia-derived, nonadherent cell lines are assayed by plating 5 × 103 cells per well in a 96-well plate. The cells are incubated with ENMD-2076 for 48 hours and then survival is assayed using the Alamar Blue reagent. To measure the effect of ENMD-2076 on VEGF- and fibroblast growth factor (FGF)-induced proliferation of human umbilical vein endothelial cell (HUVEC), cells are 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 is measured using WST-(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Src, RET, PDGFR, VEGFR, VEGFR3/FLT4, Vascular endothelial growth factor receptor, ENMD 2076, ENMD2076, ENMD-2076, Fms like tyrosine kinase 3, Fibroblast growth factor receptor, FGFR, FLT3, Inhibitor, inhibit, Platelet-derived growth factor receptor, CD135, Cluster of differentiation antigen 135, cRET, AuroraKinase, Aurora Kinase, Aurora A, Apoptosis

Compound Identifiers

PubChem CID

16041424