Home Angiogenesis FLT3 inhibitor - Aurora Kinase inhibitor - VEGFR inhibitor - FGFR inhibitor - PDGFR inhibitor - Src inhibitor - CSF-1R inhibitor - Apoptosis related activator ENMD-2076 For research use only.

ENMD-2076

ENMD-2076 has selective activity against Aurora A and Flt3 with IC50 of 14 nM and 1.86 nM, 25-fold selective for Aurora A than over Aurora B and less potent to RET, SRC, NTRK1/TRKA, CSF1R/FMS, VEGFR2/KDR, FGFR and PDGFRα. ENMD-2076 inhibits the growth of a wide range of human solid tumor and hematopoietic cancer cell lines with IC50 from 0.025 to 0.7 μM, which induces apoptosis and G2/M phase arrest. Phase 2.

ENMD-2076 Chemical Structure

ENMD-2076 Chemical Structure

CAS: 934353-76-1

Selleck's ENMD-2076 has been cited by 8 Publications

4 Customer Reviews

Purity & Quality Control

Batch: S118101 DMSO] 105 mg/mL] false] Water] 1 mg/mL] false] Ethanol] 1 mg/mL] false Purity: 99.41%
99.41

ENMD-2076 Related Products

Signaling Pathway

FLT3 Signaling Pathways

FLT3 Signaling Pathway

Choose Selective FLT3 Inhibitors

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MV4-11 Function assay Inhibition of CSF-stimulated CSF1R phosphorylation in human MV4-11 cells by immunoblotting method, IC50=0.6μM 29293000
myeloma cells Growth inhibition assay Growth inhibition of in human myeloma cells, IC50=2.99μM 28918096
Click to View More Cell Line Experimental Data

Biological Activity

Description ENMD-2076 has selective activity against Aurora A and Flt3 with IC50 of 14 nM and 1.86 nM, 25-fold selective for Aurora A than over Aurora B and less potent to RET, SRC, NTRK1/TRKA, CSF1R/FMS, VEGFR2/KDR, FGFR and PDGFRα. ENMD-2076 inhibits the growth of a wide range of human solid tumor and hematopoietic cancer cell lines with IC50 from 0.025 to 0.7 μM, which induces apoptosis and G2/M phase arrest. Phase 2.
Features Multi-target, anti-proliferative, pro-apoptotic activity, anti-angiogenic.
Targets
FLT3 [1]
(Cell-free assay)		 RET [1]
(Cell-free assay)		 Aurora A [2]
(Cell-free assay)		 VEGFR3/FLT4 [1]
(Cell-free assay)		 Src [1]
(Cell-free assay)		 Click to View More Targets
1.86 nM 10.4 nM 14 nM 15.9 nM 20.2 nM
In vitro
In vitro ENMD-2076 indicates activity against multiple kinases involved in angiogenesis, including FLT3, RET, FLT4/VEGFR3, SRC, NTRK1, CSF1R/FMS, LCK, VEGFR2/KDR, FGFR1/2, and PDGFRα with IC50 from 1.86-120 nM. ENMD-2076 inhibits the growth of a wide range of human solid tumor and hematopoietic cancer cell lines with IC50 from 0.025 to 0.7 μM, which induces apoptosis and G2/M phase arrest. ENMD-2076 induces regression or complete inhibition of tumor growth in tumor xenograft models derived from breast, colon, melanoma, leukemia, and multiple myeloma cell lines. [1] ENMD-2076 is the L (+) tartrate salt of ENMD-981693. ENMD-2076 shows significant cytotoxicity against myeloma cell lines (IM9, ARH-77, U266, RPMI 8226, MM.1S, MM.1R, NCI-H929) and primary cells with IC50 from 2.99 to 7.06 μM, which induces apoptosis. ENMD-2076 indicates low cytotoxicity to haematopoietic progenitors. ENMD-2076 inhibits the phosphoinositide 3-kinase/Akt pathway and downregulates survivin and X-linked inhibitor of apoptosis. ENMD-2076 also inhibits aurora A and B kinases, and induces G2/M cell cycle arrest. [2]
Kinase Assay Kinase assays
Recombinant Aurora A and B kinase enzymes and appropriate PanVera Z'-Lyte kinase assay kits are purchased. Assays are carried out in kinase assay buffer (50 mM of HEPES, pH 7.5, 10 mM of MgCl2, 5 mM of EGTA, 0.05% Brij-35) supplemented with 2 mM of DTT. Activities are determined at an ATP concentration equivalent to the apparent Km for each enzyme, and an enzyme concentration that results in approximately 30% phosphorylation of the peptide substrate after 1 hour. Dose–response curves of relative enzyme activity versus ENMD-2076 concentration are plotted with Grafit and used to calculate IC50 values. Potency of ENMD-2076 free base against a select panel of 100 kinase enzymes is determined using the SelectScreen kinase profiling service. ATP concentrations are at the apparent Km for each enzyme or 100 μM if the apparent Km could not be reached. Percent inhibition is determined at an ENMD-2076 free base concentration of 1 μM; for kinases where significant inhibition is noted, IC50 values are determined by generating full 10-point dose–response curves.
Cell Research Cell lines Human leukemia cell lines including MV4;11, U937, Kasumi, MO7e, HL-60, TF-1, Jurkat, K562, THP-1, Hel 92.1.7; Solid tumor cell lines and HUVEC including PANC-1, HCT116, A549, HT-29, MCF7, PC-3, BXPC-3 and HUVEC
Concentrations 0.3 nM - 125 μM
Incubation Time 48 or 96 hours
Method 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-
In Vivo
In vivo ENMD-2076 has sustained inhibitory effects on the activation of Flt3 as well as VEGFR2/KDR and FGFR1/2 in HT29 xenograft model. ENMD-2076 could prevent the formation of new blood vessels and regress formed vessels in MDA-MB-231 xenograft model. [1] Oral treatment with ENMD-2076 (50, 100, 200 mg/kg per day) inhibits the tumour growth in H929 human plasmacytoma xenografts, with significant reduction in phospho-Histone 3 (pH3), Ki-67, and angiogenesis, and also a significant increase in cleaved caspase-3. [2]
Animal Research Animal Models Tumor models including HCT-116, HT29, CT-26, A375, MDA-MB-231, H929, OPM-2, MV4;11 and HL60 are established in CB.17 SCID or NCr nude mice.
Dosages ~300 mg/kg
Administration Administered orally
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00904787 Completed
Relapsed or Refractory Hematological Malignancies
CASI Pharmaceuticals Inc.
 April 2009 Phase 1
NCT00806065 Completed
Multiple Myeloma
CASI Pharmaceuticals Inc.
 December 2008 Phase 1
NCT00658671 Completed
Advanced Cancer
CASI Pharmaceuticals Inc.
 April 2008 Phase 1

Chemical Information & Solubility

Molecular Weight 375.47 Formula

C21H25N7
CAS No. 934353-76-1 SDF Download ENMD-2076 SDF
Smiles CC1=CC(=NN1)NC2=CC(=NC(=N2)C=CC3=CC=CC=C3)N4CCN(CC4)C
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 105 mg/mL ( (279.64 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : 1 mg/mL

Ethanol : 1 mg/mL


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