ENMD-981693

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H25N7
Molecular Weight	375.4701
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

SMILES

CN1CCN(CC1)C2=CC(NC3=NNC(C)=C3)=NC(\C=C\C4=CC=CC=C4)=N2

InChI

InChIKey=BLQYVHBZHAISJM-CMDGGOBGSA-N

InChI=1S/C21H25N7/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/h3-9,14-15H,10-13H2,1-2H3,(H2,22,23,24,25,26)/b9-8+

HIDE SMILES / InChI

Molecular Formula	C21H25N7
Molecular Weight	375.4701
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description

ENMD-2076 is an orally-active, Aurora A/angiogenic kinase inhibitor. urora kinases are key regulators of mitosis (cell division), and are often over-expressed in human cancers. 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 is tested in phase 2 clinical trials against ovarian cancer, breast cance, hepatocellular carcinoma and other malignancies.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serine/threonine-protein kinase Aurora-A 37	Inhibitor 8,297	14.0 nM [IC50]
Tyrosine-protein kinase receptor FLT3 43	Inhibitor 8,297	1.86 nM [IC50]
Vascular endothelial growth factor receptor 3 41	Inhibitor 8,297	15.0 nM [IC50]
Fibroblast growth factor receptor 3 32	Inhibitor 8,297

Conditions

Condition	Modality	Highest Phase	Product
Ovarian cancer 157	Primary	Phase II 1,132	Unknown
Triple-negative breast cancer 12	Primary	Phase II 1,132	Unknown
Hepatocellular carcinoma 83	Primary	Phase II 1,132	Unknown
Fallopian tube cancer 17	Primary	Phase II 1,132	Unknown

C_max

Value	Dose	Analyte	Population
233 ng/mL	80 mg/m² 1 times / day multiple, oral	ENMD-2076 plasma	Homo sapiens
218 ng/mL	60 mg/m² 1 times / day multiple, oral	ENMD-2076 plasma	Homo sapiens
314 ng/mL	120 mg/m² 1 times / day multiple, oral	ENMD-2076 plasma	Homo sapiens
557 ng/mL	200 mg/m² 1 times / day multiple, oral	ENMD-2076 plasma	Homo sapiens
558 ng/mL	160 mg/m² 1 times / day multiple, oral	ENMD-2076 plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
14.66 μg × h/mL	80 mg/m² 1 times / day multiple, oral	ENMD-2076 plasma	Homo sapiens
15.26 μg × h/mL	60 mg/m² 1 times / day multiple, oral	ENMD-2076 plasma	Homo sapiens
16.74 μg × h/mL	120 mg/m² 1 times / day multiple, oral	ENMD-2076 plasma	Homo sapiens
34.5 μg × h/mL	200 mg/m² 1 times / day multiple, oral	ENMD-2076 plasma	Homo sapiens
34.6 μg × h/mL	160 mg/m² 1 times / day multiple, oral	ENMD-2076 plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
51 h	80 mg/m² 1 times / day multiple, oral	ENMD-2076 plasma	Homo sapiens
53.1 h	60 mg/m² 1 times / day multiple, oral	ENMD-2076 plasma	Homo sapiens
44.9 h	120 mg/m² 1 times / day multiple, oral	ENMD-2076 plasma	Homo sapiens
47.6 h	200 mg/m² 1 times / day multiple, oral	ENMD-2076 plasma	Homo sapiens
46.1 h	160 mg/m² 1 times / day multiple, oral	ENMD-2076 plasma	Homo sapiens

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1,587	inhibitor 1,767	inhibitor 1,852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1,461

Drug as perpetrator

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Target	Modality	Activity
CYP2D6 1,891	inhibitor 3,277	inconclusive [IC50 21.3174 uM]
CYP2C9 1,819	inhibitor 3,277	no
CYP3A4 1,925	inhibitor 3,277	no
P-gp 1,650	inhibitor 3,277	yes [IC50 7.3078 uM]

Showing 1 to 4 of 4 entries

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PubMed

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Title	Date	PubMed
Discovery and development of aurora kinase inhibitors as anticancer agents.	2009 May 14	19320489
Preclinical activity of a novel multiple tyrosine kinase and aurora kinase inhibitor, ENMD-2076, against multiple myeloma.	2010 Aug	20560971
ENMD-2076 is an orally active kinase inhibitor with antiangiogenic and antiproliferative mechanisms of action.	2011 Jan	21177375

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Patents

Sample Use Guides

In Vivo Use Guide

ENMD-2067 will be taken orally at a dose of 275 mg, once a day, everyday. Patients with a body surface area of less than 1.65 m2 will receive a starting dose of 250 mg, once a day, everyday.

Route of Administration: Oral

In Vitro Use Guide

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 mmol/L, for 96 hours. Cellular proliferation was measured using the sulforhodamine B (SRB; Sigma Aldrich) assay. ENMD-2076 inhibits proliferation of PANC-1, HCT116, A549 tumor cells with IC50 0.12 - 0.26 uM.

Substance Class	Chemical
Record UNII	J6U9WP10T7
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

ENMD-981693

Common Name

English

ENMD-2076 FREE BASE

Common Name

English

ENMD 981693

Code

English

4-PYRIMIDINAMINE, 6-(4-METHYL-1-PIPERAZINYL)-N-(5-METHYL-1H-PYRAZOL-3-YL)-2-((1E)-2-PHENYLETHENYL)-

Systematic Name

English

(E)-N-(5-METHYL-1H-PYRAZOL-3-YL)-6-(4-METHYLPIPERAZIN-1-YL)-2-STYRYLPYRIMIDIN-4-AMINE

Systematic Name

English

Showing 1 to 5 of 7 entries

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Code System

Code

Type

Description

FDA UNII

J6U9WP10T7

PRIMARY

SMS_ID

300000013151

PRIMARY

ChEMBL

CHEMBL52885

PRIMARY

EPA CompTox

DTXSID60239430

PRIMARY

PUBCHEM

16041424

PRIMARY

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					798536Z7S0

VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 2

TARGET -> INHIBITOR

Amount:


					KXQ762CQTH

ENMD-2076

SALT/SOLVATE -> PARENT

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Type

Details


					J6U9WP10T7

ENMD-981693

ACTIVE MOIETY

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SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Overview

OverviewOther

Drug as perpetrator​

PubMed

Patents

Sample Use Guides

C_max

T_1/2

Drug as perpetrator