ENILURACIL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C6H4N2O2
Molecular Weight	136.1082
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O=C1NC=C(C#C)C(=O)N1

InChI

InChIKey=JOZGNYDSEBIJDH-UHFFFAOYSA-N

InChI=1S/C6H4N2O2/c1-2-4-3-7-6(10)8-5(4)9/h1,3H,(H2,7,8,9,10)

HIDE SMILES / InChI

Molecular Formula	C6H4N2O2
Molecular Weight	136.1082
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1544906 | https://www.ncbi.nlm.nih.gov/pubmed/11081572 | https://www.ncbi.nlm.nih.gov/pubmed/11060767

Eniluracil (5-ethynyluracil, GW 776, 776C85) is a potent irreversible inhibitor of dihydropyrimidine dehydrogenase, the first enzyme in the catabolic pathway of 5-fluorouracil (5-FU), the most widely used drug in cancer chemotherapy. Eniluracil increases the oral bioavailability of 5-FU to 100%, facilitating uniform absorption and predictable toxicity. Eniluracil was being developed as a novel modulator of 5-FU for the treatment of cancer.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dihydropyrimidine dehydrogenase [NADP(+)] 4 Target ID: Q12882\|\|\|Q16761 Gene ID: 1806.0 Gene Symbol: DPYD Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/11060767	Inhibitor 8297		1.6 µM [Ki]

PubMed

Title	Date	PubMed
5-Ethynyluracil (776C85): protection from 5-fluorouracil-induced neurotoxicity in dogs.	1994 Jul 19	8053919
Phase II study of oral eniluracil, 5-fluorouracil, and leucovorin in patients with advanced colorectal carcinoma.	2001 Apr 1	11283924
New options for outpatient chemotherapy--the role of oral fluoropyrimidines.	2001 Aug	11545541
A phase II trial of oral eniluracil/5-fluorouracil in patients with inoperable hepatocellular carcinoma.	2001 Jul	11435064
Extraction of 5-fluorouracil by tumor and liver: a noninvasive positron emission tomography study of patients with gastrointestinal cancer.	2001 Jul 1	11431319
Advances in the treatment of metastatic colorectal cancer.	2001 May	12445376
A phase I trial of weekly paclitaxel plus prolonged oral eniluracil/5-fluorouracil in patients with refractory malignancies.	2002	12401907
Multicenter phase II study of a 28-day regimen of orally administered eniluracil and fluorouracil in the treatment of patients with anthracycline- and taxane-resistant advanced breast cancer.	2002 Feb 15	11844821
Phase I study of eniluracil and oral 5-fluorouracil in combination with docetaxel in the treatment of patients with metastatic breast carcinoma.	2002 May 1	12015755
Biochemical modulation of 5-fluorouacil through dihydropyrimidine dehydrogenase inhibition: a Southwest Oncology Group phase II trial of eniluracil and 5-fluorouracil in advanced resistant colorectal cancer.	2002 Nov	12448660
Phase I study of eniluracil, oral 5-fluororacil and gemcitabine in patients with advanced malignancy.	2002 Nov	12448654
Phase II trial of 5-fluorouracil plus eniluracil in patients with advanced pancreatic cancer: a Southwest Oncology Group study.	2002 Oct	12377645
Eniluracil's need for a targeted approach: a lesson in drug development.	2002 Sep 1	12202681
A study to evaluate the pharmacokinetics of oral 5-fluorouracil and eniluracil after concurrent administration to patients with refractory solid tumours and varying degrees of renal impairment (FUMA1005).	2003 Jan	12497207
Pharmacokinetic and pharmacodynamic effects of oral eniluracil, fluorouracil and leucovorin given on a weekly schedule.	2003 Jul	12707718
A dose-escalating study of oral eniluracil/5-fluorouracil plus oxaliplatin in patients with advanced gastrointestinal malignancies.	2003 Jun	12796023
Dihydropyrimidine dehydrogenase (DPD) rapidly regenerates after inactivation by eniluracil (GW776C85) in primary and metastatic colorectal cancer.	2003 Nov	12904894
Augmentation of the antitumor activity of capecitabine by a tumor selective dihydropyrimidine dehydrogenase inhibitor, RO0094889.	2003 Sep 20	12866042
A Phase I trial of preoperative eniluracil plus 5-fluorouracil and radiation for locally advanced or unresectable adenocarcinoma of the rectum and colon.	2004 Mar 1	14967434
The multidisciplinary management of gastrointestinal cancer. The integration of cytotoxics and biologicals in the treatment of metastatic colorectal cancer.	2007	18070705
Determination of eniluracil and 5-fluorouracil in human plasma by LC-MS/MS.	2010 Dec	21110744
A possible cause and remedy for the clinical failure of 5-fluorouracil plus eniluracil.	2010 Jan	20100689
A semi-automated non-radioactive system for measuring recovery of RNA synthesis and unscheduled DNA synthesis using ethynyluracil derivatives.	2010 May 4	20171149

Patents

Sample Use Guides

In Vivo Use Guide

Phase II study: 20 mg twice daily for a month.

Route of Administration: Oral

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:43:48 GMT 2023` Edited by `admin` on `Fri Dec 15 15:43:48 GMT 2023`
Record UNII	2E2W0W5XIU
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ENILURACIL

Official Name

English

ETHYNYLURACIL

Systematic Name

English

776C85

Code

English

eniluracil [INN]

Common Name

English

ENILURACIL [MART.]

Common Name

English

ENILURACIL [MI]

Common Name

English

776-C-85

Code

English

5-ETHYNYL-URACIL

Systematic Name

English

ENILURACIL [USAN]

Common Name

English

5-Ethynyluracil

Systematic Name

English

Eniluracil [WHO-DD]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

211505